@article{pmid42456683,

title = {Survival estimates and their predictors in genetic frontotemporal dementia: an international, retrospective, cohort study},

author = {Arabella Bouzigues and Mario Grassi and Valentina Cantoni and Enrico Premi and Sonia Bellini and Giuliano Binetti and Giancarlo Logroscino and Lucy L Russell and Eve Ferry-Bolder and Phoebe H Foster and John C van Swieten and Lize C Jiskoot and Harro Seelaar and Raquel Sanchez-Valle and Robert Laforce and Caroline Graff and Daniela Galimberti and Rik Vandenberghe and Alexandre de Mendonça and Giuseppe Di Fede and Isabel Santana and Alexander Gerhard and Tobias Langheinrich and Johannes Levin and Benedetta Nacmias and Markus Otto and Maxime Bertoux and Thibaud Lebouvier and Simon Ducharme and Christopher Butler and Isabelle le Ber and Rose Bruffaerts and Eino Solje and Mika Kinnunen and Johanna Krüger and Elizabeth Finger and Maria Carmela Tartaglia and Mario Masellis and James B Rowe and Matthis Synofzik and Fermin Moreno and Roberta Ghidoni and Raffaella Migliaccio and Jonathan D Rohrer and Barbara Borroni and },

doi = {10.1016/S1474-4422(26)00197-3},

issn = {1474-4465},

year  = {2026},

date = {2026-08-01},

journal = {Lancet Neurol},

volume = {25},

number = {8},

pages = {731--740},

abstract = {BACKGROUND: What drives the heterogeneity of survival estimates in genetic frontotemporal dementia is unknown. We sought to understand the natural history and predictors of disease trajectory, which are crucial not only for effective care but also for the design of therapeutic clinical trials and efficacy evaluation.nnMETHODS: In this international, cohort study, we used the Kaplan-Meier method to retrospectively assess survival estimates in patients enrolled in the GENFI cohort, which included 32 research sites located in Belgium, Canada, Finland, France, Germany, Italy, the Netherlands, Portugal, Spain, Sweden, and the UK, and comprised participants carrying a causal C9orf72 expansion or a causal mutation in GRN or MAPT genes. Survival was calculated as the time from symptom onset to time of death or censoring date; median survival estimate for all patients was the primary endpoint. Cox proportional hazards models were used to identify predictors of survival, which were subsequently externally validated in an independent cohort. We further designed a structural equation model to assess the relationships between predictors, applying a least absolute shrinkage and selection operator method.nnFINDINGS: Of 278 participants of the GENFI cohort included in this study, 160 (58%) were men and 118 (42%) were women. 162 died during follow-up (58%) and 116 were still alive (42%) on June 1, 2024, the chosen censoring date. 138 participants carried a C9orf72 expansion, 94 carried a GRN mutation, and 46 a MAPT mutation. 179 participants were diagnosed with behavioural variant frontotemporal dementia, 46 with primary progressive aphasia, and 31 with frontotemporal dementia-amyotrophic lateral sclerosis. 22 participants had other diagnoses. The median survival estimate for all patients with genetic frontotemporal dementia was 6·94 years (95% CI 6·59-7·80) from symptom onset. The median survival estimate for patients with GRN mutations was 6·63 years (6·08-7·98), for patients with a C9orf72 expansion was 7·04 years (6·45-8·77), and for patients with MAPT mutations was 8·56 years (7·06-13·50). Older age at onset, shorter disease duration from onset to enrolment in the GENFI study, clinical presentation (ie, frontotemporal dementia-amyotrophic lateral sclerosis), domain of first symptom (ie, motor or language onset), and geographical area of residency (ie, central and southern Europe) were associated with poorer prognosis. Genetic group did not directly affect survival estimates; rather its effect was mediated by age at onset and clinical phenotype. We computed a genetic frontotemporal dementia survival risk index, which can be used at an individual patient level.nnINTERPRETATION: Our results highlight that motor impairment in addition to cognitive and behavioural symptoms should be considered when estimating prognosis in genetic frontotemporal dementia. Individual risk scores might be of help for patient stratification in future therapeutic trials, although refinement and prospective validation are now needed.nnFUNDING: Italian Ministry of Health (Ricerca Corrente), Fondation Philippe Chatrier, and Fondation Vaincre Alzheimer.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid41608854,

title = {Individualized Atrophy-Based Prediction of Dementia Progression in Familial Frontotemporal Lobar Degeneration With Bayesian Linear Mixed-Effects Modeling},

author = {Shubir Dutt and Dana Leichter and Yann Cobigo and Amy Wolf and John Kornak and Annie Clark and Lucy L Russell and Arabella Bouzigues and David M Cash and Martina Bocchetta and Molly Olzinski and Brian Appleby and Ece Bayram and Barbara Borroni and Andrea Bozoki and Chris R Butler and David Clark and Rhian S Convery and R Ryan Darby and Alexandre de Mendonça and Bradford Dickerson and Kimiko Domoto-Reilly and Simon Ducharme and Eve Ferry-Bolder and Elizabeth Finger and Phoebe H Foster and Douglas R Galasko and Daniela Galimberti and Alexander Gerhard and Nupur Ghoshal and Caroline Graff and Neill Graff-Radford and Ian M Grant and Chadwick M Hales and Lawrence S Honig and Ging-Yuek Hsiung and Edward D Huey and David Irwin and Lize C Jiskoot and Walter Kremers and Justin Y Kwan and Robert Laforce and Isabelle Le Ber and Gabriel C Léger and Johannes Levin and Irene Litvan and Ian R Mackenzie and Mario Masellis and Mario F Mendez and Fermin Moreno and Chiadi Onyike and Markus Otto and Belen Pascual and Peter Pressman and Rosa Rademakers and Eliana Marisa Ramos and Aaron Ritter and Erik D Roberson and James B Rowe and Raquel Sanchez-Valle and Isabel Santana and Harro Seelaar and Allison Snyder and Sandro Sorbi and Matthis Synofzik and Maria Carmela Tartaglia and Pietro Tiraboschi and John C van Swieten and Marijne Vandebergh and Rik Vandenberghe and Hilary W Heuer and Bruce L Miller and William W Seeley and Maria Luisa Gorno-Tempini and Joel H Kramer and Leah Forsberg and Kejal Kantarci and Bradley F Boeve and Adam L Boxer and Jonathan D Rohrer and Howard J Rosen and Adam M Staffaroni and },

doi = {10.1002/ana.78167},

issn = {1531-8249},

year  = {2026},

date = {2026-05-01},

journal = {Ann Neurol},

volume = {99},

number = {5},

pages = {1315--1326},

abstract = {OBJECTIVE: Age of symptom onset is highly variable in familial frontotemporal lobar degeneration (f-FTLD). Accurate prediction of onset would inform clinical management and trial enrollment. Prior studies indicate that individualized maps of brain atrophy can predict conversion to dementia in f-FTLD. We used a Bayesian linear mixed-effect (BLME) prediction method for identifying accelerated brain volume loss to predict conversion to dementia.nnMETHODS: Participants included 234 asymptomatic or prodromal carriers of C9orf72, GRN, or MAPT mutations (including 21 dementia converters) with ≥3 longitudinal magnetic resonance imaging (MRI) T1-weighted scans. The BLME models established individual voxel-wise gray matter trajectories using the first 2 scans. Person-specific clusters of accelerated volume loss were estimated in subsequent scans and tested as predictors of dementia conversion compared with other approaches in time-varying Cox proportional hazard models covarying for age. Receiver-operating characteristic (ROC) curves estimated utility of cluster volume in discriminating which participants converted to dementia within 24 months.nnRESULTS: The BLME cluster volume predicted conversion to dementia in f-FTLD mutation carriers overall and separately in C9orf72, GRN, and MAPT, with comparable hazard ratios observed for atrophy W-maps and regional volumes. Within a 24-month timeframe, BLME cluster volume discriminated dementia converters from non-converters with larger areas under the curve (AUCs) than other approaches.nnINTERPRETATION: Bayesian-modeled individualized atrophy scores predict dementia progression among asymptomatic f-FTLD mutation carriers and may have increased utility compared with other structural imaging methods when studying individuals over shorter timeframes that align with clinical trial design. ANN NEUROL 20269999:n/a-n/a.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid41963707,

title = {Peripheral microRNA signature in genetic frontotemporal dementia-findings from the GENFI initiative},

author = {Chiara Fenoglio and Maria Serpente and Marina Arcaro and Tiziana Carandini and Luca Sacchi and Manuela Pintus and Vittoria Borracci and Giulia Giudici and Marta Rigoni and Paola Muti and Laura Ghezzi and Arabella Bouzigues and Lucy L Rusell and Phoebe H Foster and Eve Ferry-Bolder and John C van Swieten and Lize C Jiskoot and Harro Seelaar and Raquel Sánchez Valle and Robert Laforce and Caroline Graff and Rik Vandenberghe and Alexandre de Mendonça and Pietro Tiraboschi and Isabel Santana and Alexander Gerhard and Johannes Levin and Florence Pasquier and Simon Ducharme and Isabelle Le Ber and Elizabeth Finger and Maria Carmela Tartaglia and Mario Masellis and James B Rowe and Matthis Synofzik and Fermin Moreno and Barbara Borroni and Andrea Sacconi and Jonathan D Rohrer and Andrea Arighi and Daniela Galimberti and },

doi = {10.1007/s11357-026-02214-x},

issn = {2509-2723},

year  = {2026},

date = {2026-04-01},

journal = {Geroscience},

abstract = {Frontotemporal dementia (FTD) is a neurodegenerative disease characterized by significant clinical and genetic heterogeneity, with approximately 40% of cases linked to hereditary genetic mutations, including MAPT, GRN, and C9ORF72. Recently, microRNAs (miRNAs) have emerged as key regulators of cellular processes related to neurodegeneration and as potential biomarkers for FTD. However, their relevance in presymptomatic stages remains poorly understood. We conducted a miRNA expression analysis using TaqMan OpenArray® panels on blood samples collected from 171 individuals, including symptomatic mutation carriers (SMC), presymptomatic carriers (PMC), and healthy non-carriers (NC). Dysregulated miRNAs were validated and bioinformatic tools were used to identify potential associated molecular pathways. In C9ORF72, miR-20b-5p and miR-223-5p were significantly upregulated in SMC (fold regulation over NC: 2.418 p = 0.0336 and 7.829 p < 0.0264 respectively) and PMC (5.518, p < 0.0001 and 3.941, p < 0.0001 respectively). In GRN mutation carriers, miR-28-3p was altered in both SMC and PMC (fold regulation over NC: 1.484 p < 0.050 and 3.287, p < 0.050). In MAPT mutation carriers, miR-28-5p, miR-192-3p, miR-25-3p, and miR-532-3p were altered only in SMC (fold regulation over NC: 1.496 p < 0.050, 1.911 p = 0.006, 1.468 p < 0.05, and 0.728 p < 0.05). Bioinformatic analysis revealed enrichment of pathways related to neurodegeneration and synapse impairment. These results suggest that miRNA expression levels are deregulated in mutated SMC, in C9ORF72 and GRN PMC. Notably, miR-20b-5p, miR-223-5p, and miR-28-3p were increased in preclinical stages of the disease, supporting their role as early biomarkers for C9ORF72-FTD and GRN-FTD. Conversely, alterations in MAPT carriers appeared only in symptomatic stages, suggesting a different involvement in disease progression.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid41804764,

title = {Longitudinal association between sleep and Alzheimer's pathology},

author = {Bery Mohammediyan and Andrée-Ann Baril and Alfonso Fajardo Valdez and Frédéric St-Onge and Alexa Pichet Binette and Julie Carrier and Maiya R Geddes and Simon Ducharme and Maxime Montembeault and Jean-Paul Soucy and John Breitner and Judes Poirier and Sylvia Villeneuve and },

doi = {10.1002/alz.71228},

issn = {1552-5279},

year  = {2026},

date = {2026-03-01},

journal = {Alzheimers Dement},

volume = {22},

number = {3},

pages = {e71228},

abstract = {INTRODUCTION: Since sleep disturbance is a modifiable risk factor for Alzheimer's disease (AD), we tested associations between sleep and AD pathology in cognitively unimpaired (CU) persons.nnMETHODS: We included 223 participants from the PREVENT-AD cohort with self-reported measures of sleep, objective actigraphy measures of sleep, and positron emission tomography (PET) scans for AD pathology quantification. Repeated PET scans (mean follow-up: 4.31 ± 0.55 years) were available for 103 participants. We conducted robust linear models (RLM) for cross-sectional analyses and RLMs using the annual change in AD pathology for longitudinal analyses.nnRESULTS: All actigraphy-based sleep variability measures were associated with tau burden (duration: β = 0.121 [95% confidence interval {CI} = 0.010; 0.232], p = 0.034; efficiency: 0.122 [0.010; 0.235], 0.033; fragmentation: 0.115 [0.010; 0.221], 0.033). Greater variability in sleep fragmentation was also associated with amyloid burden (0.074 [0.008; 0.140], 0.028), and variability in sleep efficiency portended amyloid burden and faster accumulation over time (0.075 [0.009; 0.141], 0.026; 0.164 [0.008; 0.320], 0.039; respectively).nnDISCUSSION: Irregularity in sleep patterns is associated with higher pathological burden and faster amyloid accumulation.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid41679970,

title = {Composite grey matter fingerprints for genetic frontotemporal dementia},

author = {Arabella Bouzigues and Giulia Campana and Matthieu Joulot and Nicolas Gensollen and Lucy L Russell and Phoebe H Foster and Eve Ferry-Bolder and John Cornelis Van Swieten and Lize C Jiskoot and Harro Seelaar and Raquel Sánchez-Valle and Robert Laforce and Caroline Graff and Daniela Galimberti and Rik Vandenberghe and Alexandre de Mendonca and Pietro Tiraboschi and Isabel Santana and Alexander Gerhard and Johannes Levin and Sandro Sorbi and Markus Otto and Maxime Bertoux and Thibaud Lebouvier and Simon Ducharme and Chris Butler and Elizabeth Finger and Maria Carmela Tartaglia and Mario Masellis and James Benedict Rowe and Matthis Synofzik and Fermin Moreno and Barbara Borroni and Isabelle Leber and Gianluigi Zanusso and Jonathan Daniel Rohrer and Raffaella Migliaccio and },

doi = {10.1136/jnnp-2025-337186},

issn = {1468-330X},

year  = {2026},

date = {2026-02-01},

journal = {J Neurol Neurosurg Psychiatry},

abstract = {BACKGROUND: Brain structural changes in frontotemporal dementia (FTD) can occur decades before symptom onset. Precise characterisation of grey matter changes is necessary for developing models of biomarker progression, while better understanding the trajectory of the pathology is invaluable for prognosis and detecting treatment effects as we enter the era of clinical trials.nnMETHODS: Cortical and subcortical grey matter volume and thickness from structural MRI were assessed in a large cohort of 892 participants including presymptomatic and symptomatic carriers of mutations within the three main genetic causes of FTD (C9 open reading-frame 72 (C9orf72), progranulin (GRN) and microtubule-associated protein tau (MAPT)) compared with mutation-negative relatives (controls). We compared the distribution of grey matter changes of each metric at different stages of the disease cross sectionally. We aimed to identify grey matter composites for each genetic group which would show the earliest changes and which separated presymptomatic carriers from controls.nnRESULTS: While C9orf72 mutation carriers showed widespread presymptomatic grey matter changes, MAPT and particularly GRN mutation carriers showed changes more proximally to symptom onset. Our composite grey matter signatures, which discriminate asymptomatic/prodromal carriers from controls with high to very high areas under the curve, involved bilateral thalami volumes, precuneus and postcentral thickness in C9orf72; left caudal middle frontal thickness, frontal pole and pars orbitalis volumes in GRN; right temporal pole volume and left insula thickness in MAPT mutation carriers.nnCONCLUSION: We propose the use of cortical thickness and volume measurements combined from multiple regions into a composite region of interest for each FTD genetic group to identify the earliest changes and track disease progression. Our quasi-longitudinal design illustrates that these regions continue to evolve throughout the symptomatic stages. Investigating how our selected composites progress and validating these in longitudinal samples will be invaluable for future clinical trials.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid41711826,

title = {CSF protein biomarkers are associated with atrophy and symptom severity in genetic FTD: a GENFI study},

author = {Abbe Ullgren and Melissa Taheri Rydell and Sofia Bergström and Linn Öijerstedt and Jennie Olofsson and Arabella Bouzigues and Lucy L Russell and Phoebe H Foster and Eve Ferry-Bolder and John C van Swieten and Lize C Jiskoot and Harro Seelaar and Raquel Sanchez-Valle and Robert Laforce and Daniela Galimberti and Rik Vandenberghe and Alexander Gerhard and Simon Ducharme and Christopher R Butler and Elizabeth Finger and Maria Carmela Tartaglia and Mario Masellis and James B Rowe and Matthis Synofzik and Fermin Moreno and Barbara Borroni and Jonathan D Rohrer and Peter Nilsson and Elena Rodriguez-Vieitez and Anna Månberg and Eric Westman and Caroline Graff and },

doi = {10.1007/s00702-026-03118-y},

issn = {1435-1463},

year  = {2026},

date = {2026-02-01},

journal = {J Neural Transm (Vienna)},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid41097993,

title = {Serum Neurofilament Light as a Neuropsychiatric Disorder Screening Test in Psychiatric Emergency Settings},

author = {Hamza Zarglayoun and Sherri Lee Jones and Victoria Light and Katerine Rousseau and Charlotte Teunissen and Simon Ducharme},

doi = {10.1176/appi.neuropsych.20240228},

issn = {1545-7222},

year  = {2026},

date = {2026-01-01},

journal = {J Neuropsychiatry Clin Neurosci},

volume = {38},

number = {3},

pages = {272--277},

abstract = {OBJECTIVE: The authors evaluated serum neurofilament light chain (sNfL) as a blood-based biomarker to distinguish primary psychiatric disorders from psychiatric presentations of neurological or general medical etiology (i.e., neuropsychiatric disorders) in psychiatric emergency departments (PEDs), where rapid diagnosis is essential and access to advanced tests is often limited.nnMETHODS: Data were collected from 846 patients with psychiatric disorders (17% anxiety, 34% mood, 9% personality, 32% psychotic, and 7% substance use) and 20 patients with neuropsychiatric disorders (35% neurocognitive, 20% delirium, and 55% general medical causes). sNfL levels were measured with the SIMOA (Single Molecule Array) platform. Analysis of covariance and logistic regression were conducted to assess sNfL differences between psychiatric and neuropsychiatric patients. Receiver operating characteristic curve analysis was used to determine diagnostic accuracy, with Youden's index employed to identify optimal thresholds.nnRESULTS: In analyses adjusted for age and sex, patients with neuropsychiatric disorders had significantly higher sNfL levels, compared with those with psychiatric disorders. The effect size was moderate (partial η=0.24). Logistic regression confirmed that sNfL levels strongly predicted the diagnostic group. The optimal cutoff for sNfL was 30.6 pg/mL, with a sensitivity of 0.90 and specificity of 0.94. Subgroup analyses suggested that age-specific thresholds could improve diagnostic accuracy.nnCONCLUSIONS: sNfL is a promising biomarker for rapid differentiation in PEDs between primary psychiatric disorders and psychiatric conditions of general medical or neurological origins, potentially improving diagnostic accuracy and speed. Future research is needed with more diverse, prospective cohorts with a wider range of diseases to replicate the clinical utility of sNfL.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid41343108,

title = {Distinct proteomic CSF profiles in genetic frontotemporal lobar degeneration},

author = {Julie F H De Houwer and Elise G Dopper and Renee van Buuren and Marijke Stokkel and Liset de Boer and Tine Swartenbroekx and Pam A Boesjes and Ana Rajicic and Aitana Sogorb-Esteve and Arabella Bouzigues and Lucy L Russell and Phoebe H Foster and Eve Ferry-Bolder and John C van Swieten and Lize C Jiskoot and Raquel Sanchez-Valle and Robert Laforce and Caroline Graff and Daniela Galimberti and Rik Vandenberghe and Alexandre de Mendonça and Pietro Tiraboschi and Isabel Santana and Alexander Gerhard and Johannes Levin and Benedetta Nacmias and Markus Otto and Maxime Bertoux and Thibaud Lebouvier and Simon Ducharme and Chris R Butler and Isabelle Le Ber and Elizabeth Finger and Maria Carmela Tartaglia and Mario Masellis and James B Rowe and Matthis Synofzik and Fermin Moreno and Barbara Borroni and Henrik Zetterberg and Jonathan D Rohrer and Betty M Tijms and Yolande A L Pijnenburg and Charlotte Teunissen and Harro Seelaar},

doi = {10.1093/brain/awaf457},

issn = {1460-2156},

year  = {2025},

date = {2025-12-01},

journal = {Brain},

abstract = {Fluid biomarkers to diagnose frontotemporal lobar degeneration (FTLD) are currently lacking. In this study, we aimed to identify proteomic changes in cerebrospinal fluid (CSF) associated with FTLD pathogenesis, focusing on signatures unique to different genetic groups. Additionally, we sought proteins distinguishing FTLD-spectrum disorders from controls. To this end, we measured a comprehensive library of over 2900 proteins in CSF using proximity extension assay technology in two well-characterized FTLD cohorts. The discovery cohort, selected from the GENFI cohort, included 47 symptomatic pathogenic variant carriers (22 C9orf72, 14 GRN, 10 MAPT and 1 TARDBP), 124 presymptomatic pathogenic variant carriers (55 C9orf72, 44 GRN, 24 MAPT and 1 TARDBP) and 57 healthy non-carriers. The validation cohort comprised individuals clinically diagnosed with an FTLD-spectrum disorder (n = 132) and cognitively intact controls (n = 32). We assessed differentially abundant proteins using linear regression, adjusting for age and sex. Overrepresentation analysis was conducted for the three genetic groups using Gene Ontology Biological Processes as ontology source. To develop diagnostic tools, we applied a LASSO regression, establishing two types of panels: one to distinguish individuals with an FTLD-spectrum disorder from controls (FTLD panel) and another to differentiate individuals with underlying TDP pathology from controls (TDP panel). We observed 23 dysregulated proteins in symptomatic carriers. Of these, four were also significantly dysregulated (NEFL, TPM3, MSLN and DNM3) in the validation cohort. When focusing on genetic subgroups, 63 upregulated proteins were observed in symptomatic MAPT carriers, with enriched biological pathways linked to immune function. In symptomatic C9orf72 carriers, four proteins - related to energy metabolism - were upregulated. When limiting symptomatic carriers to GRN, six proteins were dysregulated, with enriched pathways involved in neuronal development and projection. Notably, NEFL and TPM3 were consistently significant in all comparisons across both cohorts. We developed two diagnostic panels: one for FTLD and one for FTLD-TDP. The FTLD panel consisted of six proteins (NEFL, RBFOX3, NPTX1, TFF1, ENTPD5, and CNP). The TDP panel was made up of seven proteins (NEFL, RBFOX3, CBLN4, ENTPD5, CCL25, CNP, and MMP1). Both panels were successfully replicated in the validation cohort (AUC of 0.94 and 0.96 respectively). This study highlights distinct proteomic signatures across FTLD genetic subgroups and their associated pathologies using a targeted proteomic approach. Additionally, we present two diagnostic panels-comprising both established and novel proteins-that effectively differentiate individuals with FTLD-spectrum disorders from healthy controls, offering promising avenues for improved clinical diagnosis.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid41068257,

title = {Cortical microstructure is associated with disease severity and clinical progression in genetic frontotemporal dementia: a GENFI study},

author = {Elena Rodriguez-Vieitez and Melissa T Rydell and Abbe Ullgren and Victor Montal and Ignacio Illán-Gala and Juan Fortea and Vesna Jelic and Arabella Bouzigues and Lucy L Russell and Phoebe H Foster and Eve Ferry-Bolder and John C van Swieten and Lize C Jiskoot and Harro Seelaar and Raquel Sanchez-Valle and Robert Laforce and Daniela Galimberti and Rik Vandenberghe and Alexandre de Mendonça and Pietro Tiraboschi and Isabel Santana and Alexander Gerhard and Johannes Levin and Sandro Sorbi and Markus Otto and Florence Pasquier and Simon Ducharme and Chris R Butler and Isabelle Le Ber and Elizabeth Finger and Maria Carmela Tartaglia and Mario Masellis and James B Rowe and Matthis Synofzik and Fermin Moreno and Barbara Borroni and Jonathan D Rohrer and Eric Westman and Caroline Graff and },

doi = {10.1038/s41380-025-03280-x},

issn = {1476-5578},

year  = {2025},

date = {2025-12-01},

journal = {Mol Psychiatry},

volume = {30},

number = {12},

pages = {5800--5812},

abstract = {The study of genetic frontotemporal dementia (FTD) allows investigating its earliest presymptomatic stages. Using cross-sectional T1-weighted and diffusion-weighted MRI, we test the hypothesis that cortical microstructural alterations, quantified as cortical mean diffusivity (cMD), are detectable earlier and are more strongly associated with clinical progression than cortical thickness (CTh). The sample comprised n = 710 individuals (47.8 ± 13.5 years, 56.6% female, 14.1 ± 3.3 years of education), including 118 symptomatic carriers and 305 presymptomatic carriers with mutations in C9orf72, GRN or MAPT genes, and 287 non-carriers, collected from 24 GENFI sites. A subset of n = 453 individuals (289 carriers, 164 non-carriers) were investigated across Clinical Dementia Rating (CDR) = 0, 0.5 and ≥1 stages. Two subsets had longitudinal clinical outcome measures, including n = 403 individuals (239 carriers, 164 non-carriers) with Cambridge Behavioural Inventory-Revised scores during 2.8 ± 1.6 years, and n = 261 individuals (164 carriers, 97 non-carriers) with CDR Sum-of-Boxes scores during 2.0 ± 0.8 years. Regional cMD and CTh were entered into linear mixed-effects models incorporating age, sex and education as covariates; site, and individual nested within site were random intercepts. The results demonstrated that cMD is more sensitive than CTh to track early cortical injury, with elevated cMD first observed at CDR = 0 in C9orf72 carriers, followed by MAPT carriers (from CDR = 0.5 stage), and by GRN carriers (beginning at CDR ≥ 1). At all stages, cortical microstructural injury had stronger effect size and was more widespread than cortical thinning. In all mutation carrier types, cMD was more strongly associated than CTh with subsequent clinical progression. Cortical microstructure is a promising biomarker to identify at-risk individuals before atrophy and clinical progression, with utility in therapeutic trials.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid41387629,

title = {Clinical recognition of frontotemporal dementia with right temporal predominance: a consensus statement from the International Working Group},

author = {Hulya Ulugut and Kyan Younes and Maxime Montembeault and Maxime Bertoux and Muireann Irish and Fiona Kumfor and Giorgio G Fumagalli and Bedia Samanci and Ignacio Illán-Gala and Jennifer C Thompson and Alexander F Santillo and Elisabet Englund and Maria Landqvist Waldö and Lina Riedl and Jan Van den Stock and Mathieu Vandenbulcke and Rik Vandenberghe and Robert Laforce and Simon Ducharme and Peter S Pressman and Paulo Caramelli and Leonardo Cruz de Souza and Leonel T Takada and Hakan Gurvit and Janine Diehl-Schmid and Daniela Galimberti and Florence Pasquier and Sandra Weintraub and Bruce L Miller and Virginia E Sturm and Jennifer L Whitwell and Bradley Boeve and Jonathan D Rohrer and Olivier Piguet and Maria Luisa Gorno-Tempini and Keith A Josephs and Julie Snowden and James B Rowe and Jason D Warren and Katherine P Rankin and Yolande A L Pijnenburg and },

doi = {10.1038/s43856-025-01252-4},

issn = {2730-664X},

year  = {2025},

date = {2025-12-01},

journal = {Commun Med (Lond)},

volume = {5},

number = {1},

pages = {523},

abstract = {Accurate diagnosis of frontotemporal dementia (FTD) with right anterior temporal lobe (RATL) predominance remains challenging due to lack of clinical characterization, and standardized terminology. The recent research of the International Working Group (IWG) identified common symptoms but also unveiled broad terminologies lacking precision and operationalization, with risk of misdiagnoses, inappropriate referrals and poor clinical management. Based on the published evidence (91267 articles screened) and expert opinion (105 FTD specialists across 52 centers) by using the nominal group technique, the IWG delineates three primary domains of impairment causing behavioral, memory and language problems: (i) multimodal knowledge of non-verbal information including people, living beings, landmarks, flavors/odors, sounds, bodily sensations, emotions and social cues; (ii) socioemotional behavior encompassing emotion expression, social response and motivation; and (iii) prioritization for focus on specific interests, hedonic valuation and personal preferences. This study establishes a consensus on clinical profile, phenotypic nomenclature, and future directions to enhance diagnostic precision and therapeutic interventions.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid41046106,

title = {Comparison of neuron-derived extracellular vesicles miRNA profile between patients with behavioural variant frontotemporal dementia and primary psychiatric disorders},

author = {Giulia Giudici and Chiara Fenoglio and Maria Serpente and Andrea Arighi and Marina Arcaro and Giuseppe Delvecchio and Paolo Brambilla and Luca Sacchi and Manuela Pintus and Vittoria Borracci and Sterre C M De Boer and Ramon Landin-Romero and Olivier Piguet and Ishana Rue and Lina Riedl and Janine Diehl-Schmid and Simon Ducharme and Glenda Halliday and Yolande A L Pijnenburg and Daniela Galimberti},

doi = {10.1016/j.nbd.2025.107132},

issn = {1095-953X},

year  = {2025},

date = {2025-11-01},

journal = {Neurobiol Dis},

volume = {216},

pages = {107132},

abstract = {The behavioural variant of frontotemporal dementia (bvFTD) often overlaps clinically with primary psychiatric disorders (PPD), leading to frequent misdiagnosis and delayed intervention. The "Diagnostic and Prognostic Precision Algorithm for behavioural variant Frontotemporal Dementia" (DIPPA-FTD) study aims to enhance bvFTD diagnosis by integrating clinical and molecular biomarkers. Among these, neuron-derived extracellular vesicles (NDEVs) isolated from plasma offer a minimally invasive means to investigate central nervous system alterations through microRNA (miRNA) profiling. This study analyzed miRNAs expression in NDEVs from patients with bvFTD, PPD, and healthy controls. In a retrospective cohort of 80 participants, six miRNAs differentiated bvFTD from PPD; however, these findings were not replicated in a prospective cohort comprised of 86 participants, suggesting heterogeneity within PPD. Further analysis identified three miRNAs (hsa-miR-106b-5p, hsa-miR-126-3p, and hsa-miR-342-3p) that significantly distinguished bvFTD from a sub-group of PPD, namely bipolar disorder (BD). The downregulation of hsa-miR-106b-5p and hsa-miR-126-3p, implicated in neuroprotection and vascular integrity, contrasted with the upregulation of hsa-miR-342-3p, which is associated with neuroinflammation. Bioinformatics analysis revealed E2F1, a transcription factor linked to autophagy and neuronal apoptosis, as a common target of significantly de-regulated miRNAs, further highlighting their potential pathophysiological role. These findings suggest that miRNAs signatures in NDEVs may serve as valuable biomarkers to differentiate bvFTD from BD, although further validation is required.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid41277710,

title = {Cellular signatures underlying functional resilience in presymptomatic frontotemporal dementia},

author = {Kamen A Tsvetanov and Maura Malpetti and P Simon Jones and Timothy Rittman and David J Whiteside and Alexander G Murley and Richard Bethlehem and Casey Paquola and Enrico Premi and Arabella Bouzigues and Lucy L Russell and Phoebe H Foster and Eve Ferry-Bolder and John C van Swieten and Lize C Jiskoot and Harro Seelaar and Raquel Sanchez-Valle and Robert Laforce and Caroline Graff and Daniela Galimberti and Rik Vandenberghe and Alexandre de Mendonça and Pietro Tiraboschi and Isabel Santana and Alexander Gerhard and Johannes Levin and Sandro Sorbi and Markus Otto and Maxime Bertoux and Thibaud Lebouvier and Simon Ducharme and Chris R Butler and Isabelle Le Ber and Elizabeth Finger and Maria Carmela Tartaglia and Mario Masellis and Matthis Synofzik and Fermin Moreno and Barbara Borroni and Jonathan D Rohrer and James B Rowe and },

doi = {10.1093/brain/awaf443},

issn = {1460-2156},

year  = {2025},

date = {2025-11-01},

journal = {Brain},

abstract = {Frontotemporal dementia (FTD) shows autosomal dominant transmission in up to a third of families, enabling the study of presymptomatic and prodromal phases. Despite self-reported well-being and normal daily cognitive functioning, brain structural changes are evident a decade or more before the expected onset of disease. This divergence between cognitive function and brain structure contrasts with the coupling of structural and functional decline after symptom onset. In healthy ageing, it has been shown that functional connectivity is a better predictor of cognitive function than volumetric structural imaging. We previously proposed that in the presymptomatic phase of genetic FTD, the maintenance of brain functional network integrity enables carriers of pathogenic variants to sustain cognitive performance. However, prior work has focused on a small number of, often predefined, networks. This provides a limited and potentially biased characterisation of the substrates and moderators of brain network integration. Here, we test the hypothesis that brain-wide functional integration in FTD determines resilience to progressive pathology before symptom onset. We assess functional connectome integration in 289 presymptomatic carriers of pathogenic variants associated with FTD using functional magnetic resonance imaging in relation to cognition and contrast with 271 family members without pathogenic variants. Because structural atrophy, functional integration and cognitive profiles are multivariate, we used canonical correlation models, supplemented by multiple linear regression models for each imaging modality. We confirmed progressive atrophy and normal cognitive function in presymptomatic carriers compared to non-carriers. Notably, functional integration was preserved in presymptomatic carriers across age, while it declined in familial non-carriers. The strongest effects were observed in cognitive control networks. The changes in functional integration in presymptomatic carriers were behaviourally relevant and independent of the severity of atrophy, suggesting a resilience mechanism in those at risk of dementia. To generate hypotheses about the genetic and neurometabolic basis of resilience, we assessed the spatial overlap between behaviourally-relevant functional integration maps and gene transcription profiles. These spatial correlations suggested resilience signatures to glial cell composition (astrocytes, microglia, oligodendrocytes), revealing cellular mechanisms inaccessible to standard neuroimaging. Our findings suggest that resilience to atrophy is associated with enhanced functional integration, protecting against clinical conversion for many years in individuals at risk of dementia. This result has implications for the design of presymptomatic disease-modifying therapy trials and gives hope for therapeutic strategies aimed at enhancing resilience and ability to maintain function despite the presence of genetically determined neuropathology.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid41259271,

title = {Neurodevelopmental effects of genetic frontotemporal dementia mutations revealed by total intracranial volume differences},

author = {Isis So and Arabella Bouzigues and Lucy L Russell and Phoebe H Foster and Eve Ferry-Bolder and John C van Swieten and Lize C Jiskoot and Harro Seelaar and Raquel Sanchez-Valle and Robert Laforce and Caroline Graff and Daniela Galimberti and Rik Vandenberghe and Alexandre de Mendonça and Pietro Tiraboschi and Isabel Santana and Alexander Gerhard and Johannes Levin and Sandro Sorbi and Markus Otto and Florence Pasquier and Simon Ducharme and Chris R Butler and Isabelle Le Ber and Maria Carmela Tartaglia and Mario Masellis and James B Rowe and Matthis Synofzik and Fermin Moreno and Barbara Borroni and Tyler Kolander and Carly Mester and Danielle Brushaber and Kejal Kantarci and Hilary W Heuer and Leah K Forsberg and Jonathan D Rohrer and Bradley F Boeve and Adam L Boxer and Howard J Rosen and Elizabeth C Finger and },

doi = {10.1177/13872877251393414},

issn = {1875-8908},

year  = {2025},

date = {2025-11-01},

journal = {J Alzheimers Dis},

volume = {109},

number = {1},

pages = {13872877251393414},

abstract = {BackgroundConverging evidence hints at neurodevelopmental effects in people at risk of genetic frontotemporal dementia (FTD).ObjectiveWe investigated total intracranial volume (TIV), a neuroimaging marker of neurodevelopment, and years of education differences between adult mutation carriers and familial non-mutation carriers, as measures of the structural and functional neurodevelopmental effects of FTD-causing genetic mutations.MethodsThis cross-sectional cohort study, facilitated through the FTD Prevention Initiative (FPI), included 902 adult pathogenic mutation carriers of , , or , and 532 familial non-carriers. ANCOVAs were computed to compare TIV and education between groups per gene. Pearson's correlations were used to examine associations between TIV and education.ResultsMutation carriers (mean ± SD age = 50.0 ± 13.2 years, sex = 55% female, () = 298, n() = 187, () = 417) were compared to familial non-carriers (age = 48.0 ± 12.9 years, sex = 58% female, () = 201, n() = 114), () = 217). Consistent with prior findings in young adults,  carriers showed larger TIV, on average by 20531 mm, compared to familial non-carriers (95% CI [85.4, 40977],  = 0.049,  = 0.008). Larger TIV correlated with higher years of education in  carriers (95% CI [0.01, 0.24], (295) = 0.12,  = 0.03) and  non-carriers (95% CI [0.08, 0.34], r(198) = 0.21,  = 0.002).  carriers demonstrated smaller TIV than non-carriers, on average by 29896 mm (95% CI [-58248, -1545],  = 0.039,  = 0.02). Models with  and education as outcome variables did not reveal significant differences.ConclusionsIn support of the neurodevelopmental hypothesis of FTD,  and  mutations are linked to structural neurodevelopmental changes in TIV. Further research is needed to identify mechanisms underlying neurodevelopmental influences of FTD mutations and ascertain their suitability as intervention targets.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid41198751,

title = {Glial and neuronal cell-free DNA in plasma of sporadic bvFTD and late onset primary psychiatric disease patients},

author = {Zac Chatterton and Sterre C M de Boer and Lina Riedl and Sophie Matis and Chiara Fenoglio and Ishana Rue and Ramon Landin-Romero and Dean Southwood and Daniela Galimberti and Andrea Arighi and Janine Diehl-Schmid and Simon Ducharme and Yolande A L Pijnenburg and Olivier Piguet and Glenda Halliday},

doi = {10.1038/s41598-025-22667-y},

issn = {2045-2322},

year  = {2025},

date = {2025-11-01},

journal = {Sci Rep},

volume = {15},

number = {1},

pages = {38844},

abstract = {Behavioral variant frontotemporal dementia (bvFTD) and primary psychiatric disorders (PPD) have symptomatic overlap that leads to diagnostic challenges. Cell-free DNA (cfDNA) tests have revolutionized prenatal non-invasive testing and cancer diagnostics. This study investigated the diagnostic potential of brain-derived cfDNA in plasma to differentiate sporadic bvFTD from PPD subjects. Targeted bisulfite sequencing was conducted to quantify glial and neuronal cfDNA levels in plasma samples from 179 bvFTD and 102 PPD subjects of the multi-center DIPPA-FTD study. No significant differences were observed in the absolute levels of glial or neuronal cfDNA between the groups. However, the neuronal-to-glial cfDNA ratio (NGR) was significantly higher in PPD cases (p = 0.0002), suggesting a relative increase in neuronal cfDNA in PPD compared to bvFTD. Diagnostic performance analysis revealed that neuronal cfDNA and NGR achieved an area under the curve (AUC) of 0.74, with a sensitivity of 90% but a specificity of 44% in distinguishing bvFTD from PPD. While increased serum levels of neurofilament light (NfL) and glial fibrillary acidic protein (GFAP) have been shown to effectively differentiate bvFTD from PPD, the addition of brain-derived cfDNA did not provide any incremental diagnostic benefit over these established biomarkers.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid41085124,

title = {Cross-country variance in facial emotion recognition in presymptomatic and symptomatic behavioral variant frontotemporal dementia: Insights from the GENFI and ReDLat consortia},

author = {Liset de Boer and Lize C Jiskoot and Harro Seelaar and John C van Swieten and Agustin Ibanez and Marcelo Maito and Sol Fittipaldi and Julie F H De Houwer and Tine Swartenbroekx and Pam A Boesjes and Rhian S Convery and Eve Ferry-Bolder and Phoebe Foster and Arabella Bouzigues and Lucy Chisman-Russell and Esther van den Berg and Janne Papma and Sanne Franzen and Renelle Bourdage and James B Rowe and Barbara Borroni and Daniela Galimberti and Pietro Tiraboschi and Mario Masellis and Elizabeth Finger and Robert Laforce and Caroline Graff and Alexander Gerhard and Raquel Sanchez-Valle and Alexandre Mendonça and Fermin Moreno and Matthis Synofzik and Rik Vandenberghe and Simon Ducharme and Isabelle Le Ber and Johannes Levin and Thibaud Lebouvier and Benedetta Nacmias and Markus Otto and Christopher R Butler and Isabel Santana and Maxime Bertoux and M Carmela Tartaglia and Jonathan D Rohrer and Jackie M Poos and },

doi = {10.1002/alz.70741},

issn = {1552-5279},

year  = {2025},

date = {2025-10-01},

journal = {Alzheimers Dement},

volume = {21},

number = {10},

pages = {e70741},

abstract = {INTRODUCTION: We investigated international differences in facial emotion recognition (FER) across stages of frontotemporal dementia (FTD). Previous studies may have missed early decline by combining data and masking variations in FER across countries.nnMETHODS: An FER test was administered to 159 individuals with behavioral variant FTD, 521 presymptomatic pathogenic variant carriers, and 583 controls from 16 countries of residence. Linear mixed models assessed age, sex, education, and country effects on FER. Voxel-based morphometry examined neural correlates across countries.nnREULTS: Country accounted for 18%-18.3% of FER variance in presymptomatic carriers and controls and 9.9% in individuals with behavioral variant of FTD (bvFTD). Cross-country differences interacted with the effects of sex, age, and education. Neural correlates involving the frontal lobe and basal ganglia were identified in individuals with bvFTD, but no cross-country differences were found.nnDISCUSSION: These results underscore the need for culturally sensitive FER tools in research and clinical practice, especially as global multinational clinical trials emerge.nnHIGHLIGHTS: Performance on a test for facial emotion recognition (FER) varies between countries. The percentage of variance is lower in the behavioral variant of frontotemporal dementia (bvFTD) compared to presymptomatic pathogenic variant carriers and healthy controls. Cross-country differences interacted with the effects of sex, age, and education. There were no differences in brain correlates of FER across countries.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid41057914,

title = {White matter hyperintensities precede other biomarkers in GRN frontotemporal dementia},

author = {Mahdie Soltaninejad and Mahsa Dadar and D Louis Collins and Reza Rajabli and Vikram Venkatraghavan and Arabella Bouzigues and Lucy L Russell and Phoebe H Foster and Eve Ferry-Bolder and John C van Swieten and Lize C Jiskoot and Harro Seelaar and Raquel Sanchez-Valle and Robert Laforce and Caroline Graff and Daniela Galimberti and Rik Vandenberghe and Alexandre de Mendonça and Pietro Tiraboschi and Isabel Santana and Alexander Gerhard and Johannes Levin and Benedetta Nacmias and Markus Otto and Maxime Bertoux and Thibaud Lebouvier and Chris R Butler and Isabelle Le Ber and Elizabeth Finger and Maria Carmela Tartaglia and Mario Masellis and James B Rowe and Matthis Synofzik and Fermin Moreno and Barbara Borroni and Jonathan D Rohrer and Yasser Iturria-Medina and Simon Ducharme and },

doi = {10.1002/alz.70695},

issn = {1552-5279},

year  = {2025},

date = {2025-10-01},

journal = {Alzheimers Dement},

volume = {21},

number = {10},

pages = {e70695},

abstract = {INTRODUCTION: Increased white matter hyperintensities (WMHs) have been reported in genetic frontotemporal dementia (FTD) in small studies, but the sequence of WMH abnormalities relative to other biomarkers is unclear.nnMETHODS: Using a large dataset (n = 763 GENFI2 participants), we measured WMHs and examined them across genetic FTD variants and stages. Cortical and subcortical volumes were parcellated, and serum neurofilament light chain (NfL) levels were measured. Biomarker progression was assessed with discriminative event-based and regression modeling.nnRESULTS: Symptomatic GRN carriers showed elevated WMHs, primarily in the frontal lobe, while no significant increase was observed in symptomatic C9orf72 or MAPT carriers. WMH abnormalities preceded NfL elevation, ventricular enlargement, and cortical atrophy. Longitudinally, baseline WMHs predicted subcortical changes, while subcortical volumes did not predict WMH changes, suggesting WMHs may precede neurodegeneration.nnDISCUSSION: WMHs are elevated in a subset of GRN-associated FTD. When present, they appear early and should be considered in disease progression models.nnHIGHLIGHTS: Elevated WMH volumes are found predominantly in symptomatic GRN. WMH accumulation is mostly observed in the frontal lobe. WMH abnormalities appear early in GRN-associated FTD, before NfL, atrophy, and ventriculomegaly. Longitudinally, WMH volumes can predict subcortical changes, but not vice versa. WMHs are key early markers in GRN-associated FTD and should be included in progression models.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid41136663,

title = {Accuracy of FDG-PET brain scan to differentiate sporadic bvFTD of mild severity from late onset psychiatric disorders},

author = {Ishana Rue and Sherri Lee Jones and Sterre C M de Boer and Mahdie Soltaninejad and Janine Diehl-Schmid and Daniela Galimberti and Andrea Arighi and Glenda Halliday and Ramon Landin-Romero and Olivier Piguet and Lina Riedl and Yolande Pijnenburg and Simon Ducharme},

doi = {10.1007/s00415-025-13467-5},

issn = {1432-1459},

year  = {2025},

date = {2025-10-01},

journal = {J Neurol},

volume = {272},

number = {11},

pages = {727},

abstract = {BACKGROUND: Positron emission tomography with [F] fluorodeoxyglucose (FDG-PET) brain scan accurately differentiates behavioral variant frontotemporal dementia (bvFTD) from other neurodegenerative disorders. However, the accuracy of FDG-PET to differentiate bvFTD from primary psychiatric disorders (PPD) remains understudied, with prior studies reporting high false positive rates.nnMETHODS: Retrospective data from the DIagnostic and Prognostic Precision Algorithm for behavioral variant Frontotemporal Dementia (DIPPA-FTD) database included 508 sporadic bvFTD and 152 late-onset PPD cases (onset at age 45-75 years). 226 cases had an FDG-PET scan completed at baseline with a visual rating for bvFTD diagnosis (Yes, No, or Ambiguous). Follow-up clinical diagnosis at least 1 year later was used as the gold standard to calculate sensitivity and specificity of FDG-PET at baseline.nnRESULTS: Follow up consisted of 198 probable bvFTD cases (87.6%) and 28 PPD cases (12.4%). FDG-PET had a sensitivity of 87% and a specificity of 93% to identify bvFTD cases, with a diagnostic accuracy of 88%. Within the PPD group, 7.1% had false positives and 14.3% had ambiguous scans. Rates of false negatives (normal or ambiguous PET) in bvFTD were 13.1% and were 2.6 times more common in males.nnCONCLUSION: FDG-PET had excellent diagnostic accuracy to differentiate between sporadic bvFTD and late onset PPD, with a low true false positive rate in PPD. False negatives were more common in males with bvFTD. These results support the use of FDG-PET as an important step in the diagnostic algorithm for patients with late onset behavioral changes, although results can be misleading in some cases.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid41020412,

title = {The PREVENT-AD cohort: Accelerating Alzheimer's disease research and treatment in Canada and beyond},

author = {Sylvia Villeneuve and Judes Poirier and John C S Breitner and Jennifer Tremblay-Mercier and Jordana Remz and Jean-Michel Raoult and Yara Yakoub and Jonathan Gallego-Rudolf and Ting Qiu and Alfonso Fajardo Valdez and Bery Mohammediyan and Mohammadali Javanray and Amelie Metz and Safa Sanami and Valentin Ourry and Alfie Wearn and Alexandre Pastor-Bernier and Manon Edde and Julie Gonneaud and Cherie Strikwerda-Brown and Christine L Tardif and Claudine J Gauthier and Maxime Descoteaux and Mahsa Dadar and Étienne Vachon-Presseau and Andrée-Ann Baril and Simon Ducharme and Maxime Montembeault and Maiya R Geddes and Jean-Paul Soucy and Natasha Rajah and Robert Laforce and Christian Bocti and Christos Davatzikos and Lune Bellec and Pedro Rosa-Neto and Sylvain Baillet and Alan C Evans and D Louis Collins and M Mallar Chakravarty and Kaj Blennow and Henrik Zetterberg and R Nathan Spreng and Alexa Pichet Binette and },

doi = {10.1002/alz.70653},

issn = {1552-5279},

year  = {2025},

date = {2025-10-01},

journal = {Alzheimers Dement},

volume = {21},

number = {10},

pages = {e70653},

abstract = {The PResymptomatic EValuation of Experimental or Novel Treatments for Alzheimer's Disease (PREVENT-AD) is an investigator-driven study that was created in 2011 and enrolled cognitively normal older adults with a family history of sporadic AD. Participants are deeply phenotyped and have now been followed annually for more than 12 years (median follow-up 8.0 years, SD 3.1). Multimodal magnetic resonance imaging (MRI), genetic, neurosensory, clinical, cerebrospinal fluid, and cognitive data collected until 2017 on 348 participants who agreed to open sharing with the neuroscience community were already available. We now share a new release including 6 years of additional follow-up cognitive data, and additional MRI follow-ups, clinical progression, new longitudinal behavioral and lifestyle measures (questionnaires, actigraphy), longitudinal AD plasma biomarkers, amyloid-beta and tau positron emission tomography (PET), magnetoencephalography, as well as neuroimaging analytic measures from all MRI modalities. We describe the PREVENT-AD study, the data shared with the global research community, as well as the model we created to sustain longitudinal follow-ups while also allowing new innovative data collection. HIGHLIGHTS: The PResymptomatic EValuation of Experimental or Novel Treatments for Alzheimer's Disease (PREVENT-AD) is a single-site longitudinal study that started in 2011 with annual follow-up data collection on individuals at risk of Alzheimer's disease who were all cognitively normal at enrolment. All 387 participants were enrolled between 2011 and 2017 and 306 (79%) of these participants were still in the study as of December 2023. While the PREVENT-AD dataset was not originally planned to be shared with the global research community, 348 participants retrospectively consented for their data to be shared with researchers worldwide. The first release of data was in 2019. We now share a second release that includes 6 years of additional follow-up visits, information on clinical progression and novel cognitive, behavioral, genetic, plasma and neuroimaging (amyloid and tau positron emission tomography [PET], magnetoencephalography [MEG], and new magnetic resonance imaging [MRI] sequences) data. It also includes analytic outputs for neuroimaging modalities.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid40605462,

title = {Accuracy of blood-based neurofilament light to different genetic frontotemporal dementia from primary psychiatric disorders},

author = {Ella Liu and Sherri Lee Jones and Victoria Light and Charlotte Teunissen and Arabella Bouzigues and Lucy L Russell and Phoebe H Foster and Eve Ferry-Bolder and John C van Swieten and Lize C Jiskoot and Harro Seelaar and Raquel Sanchez-Valle and Robert Laforce and Caroline Graff and Daniela Galimberti and Rik Vandenberghe and Alexandre de Mendonça and Pietro Tiraboschi and Isabel Santana and Alexander Gerhard and Johannes Levin and Sandro Sorbi and Markus Otto and Chris R Butler and Isabelle Le Ber and Elizabeth Finger and Maria Carmela Tartaglia and Mario Masellis and James B Rowe and Matthis Synofzik and Fermin Moreno and Barbara Borroni and Henrik Zetterberg and Jonathan D Rohrer and Simon Ducharme and },

doi = {10.1177/13872877251352103},

issn = {1875-8908},

year  = {2025},

date = {2025-07-01},

journal = {J Alzheimers Dis},

pages = {13872877251352103},

abstract = {BackgroundGenetic frontotemporal dementia (FTD) along with Alzheimer's disease (AD), is one of the most prevalent early-onset dementias. The differential diagnosis of FTD from primary psychiatric disorder (PPD) has been challenging due to significant symptom overlap, particular as FTD often presents with prolonged psychiatric prodromes.ObjectiveThis study aims to evaluate whether blood-based neurofilament light chain (NfL) can differentiate genetic FTD from PPD, and to determine a global clinical cutoff to differentiate genetic FTD carriers from PPD with high specificity and sensitivity.MethodsData (ages 40-81) were obtained from FTD mutation carriers (GENFI;  = 474;  = 120   114  = 50 ,  = 190 controls), and PPD (Biobanque Signature;  = 848). Blood-based NfL was measured with SIMOA HD-X (BbS) and SIMOA HD-1 (GENFI).ResultsBlood-based NfL was higher in all symptomatic mutations compared to PPD. Mildly symptomatic (0 < FTLD CDR-SOB-NM < 4)  and  carriers also had higher NfL. ROC curve revealed an optimal blood-based NfL cutoff of 22.1 pg/mL ( = 0.647) to distinguish symptomatic genetic FTD from PPD (78.5% sensitivity, 86.2% specificity, AUC = 0.908). For mildly symptomatic subjects, a cutoff of 16.2 pg/mL ( = 0.601) differentiated groups with 86.7% sensitivity and 73.5% specificity (AUC = 0.870).ConclusionsNfL holds potential as a blood-based biomarker for symptomatic genetic FTD carriers, with moderate accuracy to distinguish PPD from mild forms including .},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid40424598,

title = {Anatomical progression of genetic frontotemporal lobar degeneration across the lifespan},

author = {Vincent Planche and Boris Mansencal and Vladimir Fonov and José V Manjon and Thomas Tourdias and Arabella Bouzigues and Lucy L Russell and Phoebe H Foster and Eve Ferry-Bolder and John C van Swieten and Lize C Jiskoot and Harro Seelaar and Raquel Sanchez-Valle and Robert Laforce and Caroline Graff and Daniela Galimberti and Rik Vandenberghe and Alexandre de Mendonça and Pietro Tiraboschi and Isabel Santana and Alexander Gerhard and Johannes Levin and Sandro Sorbi and Markus Otto and Maxime Bertoux and Thibaud Lebouvier and Chris R Butler and Isabelle Le Ber and Elizabeth Finger and Maria Carmela Tartaglia and Mario Masellis and James B Rowe and Matthis Synofzik and Fermin Moreno and Barbara Borroni and Jonathan D Rohrer and D Louis Collins and Simon Ducharme and Pierrick Coupé and },

doi = {10.1093/brain/awaf195},

issn = {1460-2156},

year  = {2025},

date = {2025-05-01},

journal = {Brain},

abstract = {The recent development of brain charts for the human lifespan offers an ideal modeling framework for pathologies such as genetic frontotemporal lobar degeneration (FTLD) which likely involve both neurodevelopmental and neurodegenerative processes over a lifetime. We have therefore combined this new methodological approach with MRI data from asymptomatic and symptomatic subjects, carrying C9orf72, MAPT or GRN mutations from the GENFI and ALLFTD cohorts. We analyzed 37,532 MRIs from control subjects covering the entire lifespan and a total of 1,341 MRIs from subjects with a pathogenic FTLD mutation, aged from 18 to 86 years old. We detected the first significant regional brain volume differences on average at 27 years old in C9orf72 and MAPT mutation carriers, and at 42 years old in GRN mutation carriers. The delay between the onset of anatomical changes and the average age of symptom onset (i.e. the presymptomatic phase) was 13 years for MAPT, 17 years for GRN, and 34 years for C9orf72 mutation carriers. In terms of effect size, cumulative atrophy over the lifespan was twice as severe in affected brain regions in MAPT than in GRN or C9orf72 mutation carriers. However, the neurodegenerative process was spatially more extensive in C9orf72 (35 brain regions affected out of the 61 tested) compared to GRN or MAPT mutations carriers (25 and 18 regions, respectively). Schematically, the chronological staging of atrophy progression showed an initial involvement of the thalamus in C9orf72 expansion carriers, followed by the fronto-temporo-insular regions, the striatum and the amygdala. In GRN mutation carriers, atrophy began in fronto-insular areas, before progressing toward subcortical structures. In MAPT mutation carriers, atrophy affected the anterior temporal pole with the amygdala and hippocampus, before progressing to fronto-insular regions and the striatum. Our results using brain charts for the human lifespan show that C9orf72 is the most diffuse but also the slowest to emerge among genetic FTLD. MAPT FTLD is more aggressive and focal, while GRN FTLD is also rapidly progressive but with a later onset of the presymptomatic phase. Beyond quantification of the anatomical progression of genetic FTLD over the lifespan, these results may help determine the best timing to model and test disease-modifying strategies in FTLD, and monitor their effect in future clinical trials.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}