@article{pmid42168643,

title = {Visual versus quantitative tau-PET Braak staging in Alzheimer's disease using [F]MK6240},

author = {Arthur C Macedo and Karine Provost and Jean-Paul Soucy and Arlette Haeger and Joseph Therriault and Lydia Trudel and Nesrine Rahmouni and Jaime Fernandez-Arias and Étienne Aumont and Aurélie Lebrun and Tevy Chan and Seyyed Ali Hosseini and Gleb Bezgin and Cécile Tissot and Stijn Servaes and Brandon Hall and Jenna Stevenson and Robert Hopewell and Chris Hung-Hsin Hsiao and Gallen Triana-Baltzer and Hartmuth C Kolb and Andréa L Benedet and Gassan Massarweh and Jesse Klostranec and Paolo Vitali and Tharick A Pascoal and Pedro Rosa-Neto},

doi = {10.1007/s00259-026-07886-3},

issn = {1619-7089},

year  = {2026},

date = {2026-08-01},

journal = {Eur J Nucl Med Mol Imaging},

volume = {53},

number = {10},

pages = {5644--5658},

abstract = {PURPOSE: The 2024 Alzheimer's Association Workgroup research framework designates tau proteinopathy (T) as a key element for Alzheimer's disease (AD) staging, but optimal staging approaches have yet to be determined. Here, we compared visual and quantitative tau-PET-based Braak staging as candidate strategies to implement T biological staging in vivo.nnMETHODS: We included 140 participants from the TRIAD cohort who underwent [⁸F]MK6240 tau-PET. Quantitative Braak staging (qBraak) was derived from regional SUVR thresholds, whereas visual Braak staging (vBraak) was independently performed by three nuclear medicine physicians using an adapted interpretation algorithm. Inter-rater and inter-method agreement were assessed using Cohen's and Fleiss' κ statistics. Associations with clinical severity, cortical thickness, plasma pTau217, and cortical tau extent were examined. Diagnostic performance for identifying amyloid-positive cognitively impaired individuals was evaluated.nnRESULTS: vBraak demonstrated substantial to nearly perfect inter-rater agreement (κ = 0.65-0.93). Agreement between vBraak and qBraak was moderate when stages were treated categorically (κ = 0.51), but substantial when their ordinal nature was considered (weighted κ up to 0.73). Both strategies showed comparable associations with clinical severity and neurodegeneration. vBraak was more sensitive to amyloid-β-positive cognitive impairment and identified intermediate-stage involvement at lower global tau extent. Visual-quantitative discordant cases were primarily attributable to off-target binding or spatially heterogeneous tau patterns.nnCONCLUSION: Both vBraak and qBraak staging provide complementary and largely concordant approaches for operationalizing T staging. Quantitative methods enable scalable, group-level analyses, whereas visual assessment remains essential for identifying atypical tau patterns and informing clinically relevant decision-making.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid42422935,

title = {Validation and normative data for the Multilingual Naming Test (MINT) in French-speaking Quebec adults over 40},

author = {Felix-Etienne Colpron-Larin and Etienne Aumont and Samantha Schwartz and Laura-Maria Perez and Nesrine Rahmouni and Arthur Casa Macedo and Lydia Trudel and Delphine Oliva Lopez and Brandon Hall and Anna Marier and Thomas Carrier and Marie-Anne St-Georges and Jean-Christophe Maranda and Jenna Stevenson and Paolo Vitali and Maxime Montembeault and Pedro Rosa-Neto},

doi = {10.1080/23279095.2026.2700399},

issn = {2327-9109},

year  = {2026},

date = {2026-07-01},

journal = {Appl Neuropsychol Adult},

pages = {1--12},

abstract = {Picture naming tests are critical tools for assessing language and semantic memory deficits in dementia, but must be adapted to local cultural context. This study aimed to develop and validate a Quebec French version of the Multilingual Naming Test (MINT), including determining norms and assessing diagnostic accuracy of mild cognitive impairment (MCI) and dementia. Quebec French-speaking participants ( = 224) were drawn from the TRIAD Montreal cohort and the DEVOCS study and stratified into three subgroups using a double-threshold of quantitative (Montreal Cognitive Assessment) and qualitative (consensus diagnosis) assessments. Linear models were used to create norms and compare diagnostic groups; correspondence with the Boston Naming Test (BNT) used the equipercentile method. Item-specific analysis revealed that naming of three items was sex-dependent. We found significant effects of sex and education, and an interaction trend, on uncued MINT scores. The MINT showed high comparability to the BNT, and Receiver Operating Characteristic curves corroborated their similar diagnostic ability. The MINT performed better at discriminating dementia from cognitively unimpaired participants than at identifying MCI. Correcting for education and sex was necessary to obtain accurate scores. Our results show that the MINT is adequately valid and effective to replace the BNT in neuropsychological assessment in the Quebec French population.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid42092769,

title = {Home-based physical exercice with additional cognitive training for improving mobility in older adults: a secondary analysis of the COVEPIC randomized controlled trial},

author = {Emma Gabrielle Dupuy and Caroll-Ann Blanchette and Florent Besnier and Christine Gagnon and Thomas Vincent and Tudor Vrinceanu and Juliana Breton and Kathia Saillant and Josep Iglesies-Grau and Sylvie Belleville and Martin Juneau and Paolo Vitali and Anil Nigam and Mathieu Gayda and Louis Bherer},

doi = {10.1186/s11556-026-00415-z},

issn = {1813-7253},

year  = {2026},

date = {2026-05-01},

journal = {Eur Rev Aging Phys Act},

abstract = {BACKGROUND: Home-based physical exercise is an accessible strategy to help maintain physical functioning in adults over 50, but mobility gains may be limited without direct supervision. By improving cognitive processes involved in motor control, cognitive training may help enhance the effectiveness of home-based physical exercise in preventing age-related decline in mobility. This study compares the effects of a six-month home-based physical exercise, with or without cognitive training, on gait speed and balance.nnMETHODS: 127 community-dwelling adults aged 50-87 years (mean 65.20 ± 7.93; 76% women) were randomly assigned to (1) home-based, remotely monitored physical exercise alone (n = 64; 72% women) or (2) combined with cognitive training (n = 63; 81% women) for six months. The primary outcome was the change from baseline in usual gait speed, measured by the 4-meter walking test. Secondary outcomes included fast gait speed, balance (one-leg stance test), and lower-limb strength (five-time sit-to-stand test), all of which were assessed via videoconference at 3 and 6 months. Changes in outcomes were analyzed using adjusted mixed linear models with intervention group, time (ΔT0-T3, ΔT0-T6), and their interaction as fixed effects.nnRESULTS: Change in usual gait speed did not differ between groups. In contrast, the combined group showing greater improvements than the physical exercise alone group in fast gait speed (+ 0.07 m/s; F(1,199) = 6.24, p = 0.013, ηp ≃0.03) and one-leg balance test (+ 3.83 s; F(1,202) = 6.05, p = 0.015, ηp ≃0.03) in response to intervention. No significant group × time interaction was observed, indicating similar changes at 3 and 6 months.nnCONCLUSION: Adding cognitive training to home-based physical exercise may improve fast gait speed and balance in adults aged 50 and above. These findings support the interplay between sensorimotor and cognitive functions in older adults and suggest that combined physical and cognitive interventions could help prevent age-related mobility decline.nnCLINICAL TRIAL REGISTRATION ID: COVEPIC was retrospectively registered on November 19, 2020.nnCLINICAL TRIAL IDENTIFIER: NCT04635462. https://clinicaltrials.gov/ct2/show/record/NCT04635462?term=NCT04635462&draw=2&rank=1.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid41978994,

title = {Elevation in network dynamics amplifies amyloid-dependent tau pathology},

author = {Jieying Li and Yang Yi and Lin Gan and Gleb Bezgin and Tevy Chan and Nesrine Rahmouni and Yi-Ting Wang and Etienne Aumont and Seyyed Ali Hosseini and Brandon J Hall and Lydia Trudel and Joseph Therriault and Arthur C Macedo and Kely Monica Quispialaya Socualaya and Jaime Fernandez Arias and Yansheng Zheng and Delphine Olivia-Lopez and Robert Hopewell and Chris Hung-Hsin Hsiao and Ting Zou and Jean-Paul Soucy and Serge Gauthier and Paolo Vitali and Tharick A Pascoal and Qolamreza R Razlighi and Maxime Montembeault and Rong Li and Pedro Rosa-Neto},

doi = {10.1002/alz.71354},

issn = {1552-5279},

year  = {2026},

date = {2026-04-01},

journal = {Alzheimers Dement},

volume = {22},

number = {4},

pages = {e71354},

abstract = {INTRODUCTION: The role of brain network dynamics in relation to amyloid beta (Aβ) and tau pathology across Braak stages remains unclear.nnMETHODS: In this cross-sectional study of 216 participants from Translational Biomarkers of Aging and Dementia (TRIAD) cohort, we analyzed resting-state functional magnetic resonance imaging using a multilayer modularity algorithm to assess brain network dynamics across 10 predefined functional networks, stratified by amyloid and tau positron emission tomography biomarkers and Braak stages.nnRESULTS: Switching rates were significantly elevated in Aβ-positive/tau-positive individuals relative to Aβ-negative/tau-negative individuals, and increased progressively with advancing Braak stages. Elevated switching rates were strongly correlated with Aβ and tau burden in dorsal attention network and sensorimotor network, as well as with cognitive severity. Importantly, the interaction between network switching rate and Aβ burden synergistically contributed to accelerated tau accumulation in Braak stage III to V regions.nnDISCUSSION: These findings support the framework that increased network switching may amplify Aβ-related tau load and cognitive deterioration in Alzheimer's disease.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid41722275,

title = {Estimated prevalence of underdiagnosed dementia in a multiethnic community-based study},

author = {Lydia Trudel and Joseph Therriault and Arthur C Macedo and Meredith N Braskie and Karin L Meeker and Arthur W Toga and Serge Gauthier and Paolo Vitali and Sid E O'Bryant and Pedro Rosa-Neto},

doi = {10.1016/j.tjpad.2026.100510},

issn = {2426-0266},

year  = {2026},

date = {2026-04-01},

journal = {J Prev Alzheimers Dis},

volume = {13},

number = {4},

pages = {100510},

abstract = {Dementia frequently goes undetected in community settings, particularly among socially disadvantaged populations. Here, we estimated the prevalence of underdiagnosed dementia across diverse sociodemographic determinants of health in the Health and Aging Brain Study-Health Disparities (HABS-HD), a community-based cohort of adults recruited through community outreach in Fort Worth, Texas. We estimated age-specific probabilities of underdiagnosis using Poisson regression models with a log link, including age and sex as covariates. Robust (sandwich) variance estimators were used to obtain standard errors and 95% confidence intervals (CI). Group differences or trends for continuous measures were assessed using robust variance estimates. The prevalence of underdiagnosed dementia was higher among individuals without physician access (98.1% vs. 78.1%, p<.0001), non-English speakers (97.9% vs. 76.8%, p<.0001), and the uninsured (91.5% vs. 79.5%, p=.03). Black and Hispanic participants also showed higher prevalence (85.8% and 90.9%) compared to non-Hispanic White participants (64.9%; p=.02 and p=.002, respectively). Each additional year of education was associated with a 2.5% lower risk of underdiagnosis (p<.0001). No differences were observed by sex, marital status, income or social support. Our results highlight that several sociodemographic factors contribute to the likelihood of living with undiagnosed dementia.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid41650358,

title = {Association of Cortical Free Water With Brain Tau Tangle Load in the Alzheimer Disease Continuum},

author = {Brandon J Hall and Etienne Aumont and Seyyed Ali Hosseini and Jaime Fernandez Arias and Arnaud Boré and Gleb Bezgin and Lydia Trudel and Tevy Chan and Joseph Therriault and Arthur C Macedo and Marcel Seungsu Woo and Delphine Oliva-Lopez and Nesrine Rahmouni and Yansheng Zheng and Stijn Servaes and Jenna Stevenson and Serge Gauthier and Andrea L Benedet and Matthieu Dumont and Jean-Christophe Houde and Gallen Triana-Baltzer and Hartmuth Christian Kolb and Nicholas J Ashton and Henrik Zetterberg and Yasser Iturria Medina and Paolo Vitali and Maxime Descoteaux and Jesse Michael Klostranec and Tharick Pascoal and Pedro Rosa-Neto},

doi = {10.1212/WNL.0000000000214606},

issn = {1526-632X},

year  = {2026},

date = {2026-03-01},

journal = {Neurology},

volume = {106},

number = {5},

pages = {e214606},

abstract = {BACKGROUND AND OBJECTIVES: Neurofibrillary tangles (NFTs) progressively damage gray matter in Alzheimer disease (AD). Resulting cortical microstructural alterations might not be detectable using macrostructural metrics but may be studied using isotropic water diffusion, as it reflects extracellular free water content. The aim of this study was to examine the effect of NFTs on cortical microstructure by investigating whether cortical free water increases as a function of tau load. We also investigated whether phosphorylated tau in blood plasma also indicated cortical microstructural abnormalities.nnMETHODS: For this cross-sectional study, we sampled participants with T1 MRI, multishell diffusion-weighted MRI, amyloid PET ([F]AZD4694), tau PET, and plasma phosphorylated tau 217+ (p-tau217) from the Translational biomarkers in Aging and Dementia cohort at McGill University; participants were recruited between 2017 and 2024. We used the Neurite Orientation Dispersion and Density Imaging algorithm to calculate isotropic free water images ("free water"). FreeSurfer was used to calculate cortical thickness in the entorhinal, fusiform, inferior temporal, and middle temporal gyri regions of interest ("meta-ROI"); Automatic Segmentation of Hippocampal Subfields was used to calculate hippocampal volumes. We grouped participants by amyloid PET positivity (A), plasma p-tau217 positivity (T1), and tau PET positivity (T2). We performed voxel-wise correlation analyses between free water and these proteinopathy markers, as well as ROI-based analyses in the meta-ROI.nnRESULTS: A total of 303 participants (mean age 67 years, 58.7% female) were included in this study (168 cognitively normal individuals, 43 with mild cognitive impairment, 23 with AD dementia, 68 not diagnosed). Tau PET was positively correlated with free water in gray matter predominantly in the temporal lobe (partial  = 0.39,  < 0.001), and the correlation of p-tau217 with the meta-ROI free water was entirely mediated by tau PET ( < 0.001). In addition, medial temporal and hippocampal free water was negatively correlated with Montreal Cognitive Assessment scores in the A-T+ and A+T+ groups. The strongest ROI-based multilinear models for predicting temporal gray matter and hippocampal tau PET burden used both cortical thickness and free water as predictors (temporal gray matter partial  = 0.62; hippocampal partial  = 0.64).nnDISCUSSION: In AD-relevant regions, increased free water correlates with tau load independently of macrostructural metrics or amyloid load. Free water may serve as an imaging marker for microstructural changes in gray matter resulting from NFT accumulation, complementary to macrostructural metrics.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid41816928,

title = {Language deficits across PET-based Braak stages of tau accumulation in Alzheimer's disease},

author = {Anna Marier and Jaime Fernández Arias and Étienne Aumont and Brandon J Hall and Arthur C Macedo and Nesrine Rahmouni and Gleb Bezgin and Paolo Vitali and Pedro Rosa-Neto and Maxime Montembeault},

doi = {10.1002/alz.71286},

issn = {1552-5279},

year  = {2026},

date = {2026-03-01},

journal = {Alzheimers Dement},

volume = {22},

number = {3},

pages = {e71286},

abstract = {INTRODUCTION: Language complaints in cognitively unimpaired (CU) individuals may reflect Alzheimer's Disease (AD) pathology and future objective impairments.nnMETHODS: 211 participants (138 CU, 45 with mild cognitive impairment (MCI), and 28 with dementia) from the TRIAD cohort underwent F-MK-6240 tau-PET and F-AZD-4694 amyloid-PET. Word-finding complaints, confrontation naming, semantic fluency, phonemic fluency and word-knowledge were evaluated.nnRESULTS: Complaints about forgetting the names of objects appeared in early tau stages (Braak 1-2), followed by naming difficulties (Braak 3-4), and widespread language impairments in later stages (Braak 5-6). Across the biologically-defined AD continuum, lower language performance was associated with tau accumulation predominantly in left-temporal language regions. In CU, only subjective word-finding complaints related to tau, indicating language concerns could reflect underlying pathology before measurable cognitive decline.nnDISCUSSION: Language measures support early detection and staging of AD pathophysiology and contribute to better align cognitive assessment with biological definitions of the disease.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid41738400,

title = {Choroidal-ventricular system abnormalities are linked to amyloid-β aggregation in Alzheimer's disease},

author = {Seyyed Ali Hosseini and Etienne Aumont and Nesrine Rahmouni and Marcel S Woo and Arthur C Macedo and Brandon Hall and Tevy Chan and Joseph Therriault and Lydia Trudel and Yansheng Zheng and Gleb Bezgin and Aurélie Lebrun and Jaime Fernandez Arias and Kely Quispialaya Socualaya and Cécile Tissot and Stijn Servaes and Yi-Ting Wang and Delphine Oliva-Lopez and Stuart Mitchell and Robert Hopewell and Chris Hung-Hsin Hsiao and Catherine Saleh and Jenna Stevenson and Firoza Lussier and Liyong Wu and Min Chu and Sanjeev Chawla and Vladimir Fonov and Gassan Massarweh and Yasser Iturria Medina and Jean-Paul Soucy and Karine Provost and David A Rudko and Thomas Karikari and Andréa Lessa Benedet and Nicholas J Ashton and Henrik Zetterberg and Maxime Montembeault and Paolo Vitali and Kaj Blennow and Serge Gauthier and D Louis Collins and Jesse Klostranec and Tharick A Pascoal and Pedro Rosa-Neto},

doi = {10.1002/alz.71205},

issn = {1552-5279},

year  = {2026},

date = {2026-02-01},

journal = {Alzheimers Dement},

volume = {22},

number = {2},

pages = {e71205},

abstract = {INTRODUCTION: Enlargement of the choroidal-ventricular system occurs in aging and Alzheimer's disease (AD), but emerging evidence links these abnormalities to amyloid beta (Aβ) aggregation. We tested this hypothesis by assessing associations between AD pathophysiology and choroidal-ventricular system measures across the AD continuum.nnMETHODS: Ventricular volume, choroid-plexus volume, and ventricular radioactivity after positron emission tomography (PET) tracer injections were analyzed in 385 Translational Biomarkers in Aging and Dementia (TRIAD) and 282 Alzheimer's Disease Neuroimaging Initiative (ADNI) participants using linear models and partial correlations. A composite score combining these measures was also tested against established AD biomarkers.nnRESULTS: With advancing AD stages, ventricular and choroid-plexus volumes increased while ventricular radioactivity declined. These measures were interrelated, and abnormalities appeared even in amyloid-negative elderly. Across cohorts, they correlated with amyloid- and tau-PET, cerebrospinal fluid (CSF) and plasma p-tau isoforms, glial fibrillary acidic protein (GFAP), and cognition. Voxel-wise analyses showed strong associations with cortical Aβ, mediating downstream tau effects.nnDISCUSSION: Changes in the choroidal-ventricular system are mutually correlated and carry an additive-effect on cortical Aβ load.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid41656561,

title = {Quantitative susceptibility mapping of the brain is associated with inflammatory changes in Alzheimer's disease related areas},

author = {Seyyed Ali Hosseini and Stijn Servaes and Arthur C Macedo and Etienne Aumont and Nesrine Rahmouni and Tevy Chan and Joseph Therriault and Lydia Trudel and Brandon Hall and Yi-Ting Wang and Jaime Fernandez Arias and Gleb Bezgin and Yansheng Zheng and Marina P Gonçalves and Kely Quispialaya Socualaya and Marcel S Woo and Cécile Tissot and Delphine Oliva-Lopez and Jieying Li and Stuart Mitchell and Aurélie Lebrun and Robert Hopewell and Sanjeev Chawla and Vladimir Fonov and Gassan Massarweh and Yasser Iturria Medina and Jean-Paul Soucy and Maxime Montembeault and Paolo Vitali and Kaj Blennow and Thomas K Karikari and Andréa L Benedet and Nicholas J Ashton and Henrik Zetterberg and Tharick A Pascoal and Serge Gauthier and Jesse Klostranec and Hangwei Zhuang and Junghun Cho and D Louis Collins and Yi Wang and David A Rudko and Pedro Rosa-Neto},

doi = {10.1177/0271678X261417193},

issn = {1559-7016},

year  = {2026},

date = {2026-02-01},

journal = {J Cereb Blood Flow Metab},

pages = {271678X261417193},

abstract = {Accumulation of paramagnetic substances in brain tissue may constitute a feature of Alzheimer's disease (AD) associated with inflammatory processes. This study employed MRI quantitative susceptibility mapping (QSM), as an index of paramagnetic load, to assess its association with brain Aβ and tau aggregates, as well as inflammatory biomarkers. We assessed QSM and T1-weighted MRI scans from 315 participants in the TRIAD cohort, including young-controls and individuals across the AD spectrum. Imaging was performed at baseline, with follow-up assessments at 12 and 24 months. Mean-cortical and subcortical susceptibility values were measured, and correlations with AD-relevant plasma and CSF inflammatory biomarkers. At baseline, AD patients had significantly greater QSM than age-matched controls in the posterior cingulate cortex, precuneus, and basal ganglia. After 24 months, QSM increased in the anterior cingulate in MCI, while dementia cases showed increase in the pallidum and hippocampus. Multiple comparison analysis indicated correlation between QSM and immune biomarkers IL-10RB, PD-L1, SCF, TWEAK, CSF-1, CXCL9, HGF, and CD40, but not with brain Aβ or tau-related biomarkers. Our findings reveal that the magnitude of tissue susceptibility load, as measured by QSM, reflects tissue inflammation rather than protein aggregation. QSM provides new insights into tissue dysfunction, with potential applications in AD therapeutic development.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid41853044,

title = {Ventricular enlargement is associated with early Alzheimer's disease pathophysiology},

author = {Seyyed Ali Hosseini and Etienne Aumont and Nesrine Rahmouni and Marcel S Woo and Arthur C Macedo and Brandon Hall and Lydia Trudel and Tevy Chan and Jaime Fernandez Arias and Yi-Ting Wang and Stijn Servaes and Joseph Therriault and Yansheng Zheng and Kely Quispialaya Socualaya and Gleb Bezgin and Cécile Tissot and Delphine Oliva-Lopez and Robert Hopewell and Chris Hung-Hsin Hsiao and Catherine Saleh and Jenna Stevenson and Firoza Lussier and Liyong Wu and Min Chu and Sanjeev Chawla and Vladimir Fonov and Gassan Massarweh and Yasser Iturria-Medina and Jean-Paul Soucy and David A Rudko and Serge Gauthier and Thomas Karikari and Andréa Lessa Benedet and Nicholas J Ashton and Henrik Zetterberg and Maxime Montembeault and Paolo Vitali and Kaj Blennow and D Louis Collins and Jesse Klostranec and Tharick A Pascoal and Pedro Rosa-Neto},

doi = {10.1093/braincomms/fcag066},

issn = {2632-1297},

year  = {2026},

date = {2026-01-01},

journal = {Brain Commun},

volume = {8},

number = {2},

pages = {fcag066},

abstract = {Alzheimer's disease (AD) is characterized by progressive brain changes, including protein aggregation and structural changes. Cerebrospinal fluid (CSF) system abnormalities, such as ventricular dilation, increased choroid plexus volume or positron emission tomography (PET) ligand uptake in the CSF, have also been consistently described. We aimed to examine whether changes in CSF production and clearance might be associated with brain protein aggregation across biological stages of Alzheimer's disease. We hypothesized an association between brain protein aggregation and changes on the CSF system. We examined 378 individuals from the Translational Biomarkers in Aging and Dementia (TRIAD) cohort with T1-weighted magnetic resonance imaging (MRI), amyloid-PET and tau-PET assessments. We assessed the lateral ventricle and choroid plexus volumes, both corrected for intracranial volume, in the MRI native space. Non-specific ventricular tracer standardized uptake value ratio (SUVR), derived from amyloid- and tau-PET images, was used as an indirect marker of choroid plexus-related clearance activity and served as a metric of CSF dynamics. Linear models tested associations amongst lateral ventricular volume (reflecting CSF space enlargement), choroid plexus volume (reflecting secretory tissue morphology) and ventricular SUVR (reflecting tracer activity within the CSF compartment and serving as an indirect marker of choroid plexus-related clearance function and CSF dynamics) with Aβ and tau aggregations. Analyses were restricted to within-modality associations, relating ventricular radioactivity to cortical pathology for each PET tracer. We found that when considered independently, larger ventricular and choroid plexus volumes were associated with higher neocortical Aβ-PET SUVR, particularly in the precuneus and cingulate cortices. Additionally, lower ventricular radioactivity (derived from amyloid-PET) showed strong negative associations in the dorsal apex of the neocortex. However, when all three ventricular parameters were included in the same model, these effects were mediated by ventricular volume. By contrast, the effect of the ventricular parameters on tau load was mediated by Aβ in the neocortex. Therefore, ventricular enlargement appears to be associated with Aβ load. Distinct from neurodegeneration, changes in ventricular parameters, particularly ventricular volume, are associated with upstream Alzheimer's disease pathophysiology. While ventricular volume significantly mediated ventricular amyloid clearance, no such effect was observed for tau, suggesting distinct clearance mechanisms for these pathologies in Alzheimer's disease.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid41556545,

title = {Clinical-biological Alzheimer's disease stage concordance: insights from cohorts and autopsy data},

author = {Lydia Trudel and Joseph Therriault and Arthur C Macedo and Seyyed A Hosseini and Jaime Fernandez-Arias and Tevy Chan and Nesrine Rahmouni and Gleb Bezgin and Cécile Tissot and Marcel S Woo and Étienne Aumont and Yansheng Zheng and Brandon Hall and Delphine Oliva-Lopez and Stuart W Mitchell and Robert Hopewell and Chris Hung-Hsin Hsiao and Arthur W Toga and Meredith N Braskie and Karin L Meeker and Jean-Paul Soucy and Marie-Christine Guiot and Serge Gauthier and Paolo Vitali and Sid E O'Bryant and Tharick A Pascoal and Pedro Rosa-Neto},

doi = {10.1093/brain/awag018},

issn = {1460-2156},

year  = {2026},

date = {2026-01-01},

journal = {Brain},

abstract = {Alzheimer's disease (AD) is defined by its characteristic neuropathologic changes, which allow for diagnosis and assessment of severity. Recently, the Alzheimer's Association proposed a framework to stage Alzheimer's disease biologically based on tau-PET. Furthermore, the framework hypothesizes a degree of alignment between biological Alzheimer's disease severity and clinical symptom severity. We aimed to investigate the concordance between clinical and biological stages of Alzheimer's disease and explore factors contributing to discordance using in vivo and postmortem neuropathological data. Data from 768 amyloid-β positive individuals were drawn from four observational cross-sectional in vivo cohorts-TRIAD, ADNI, HABS-HD, and SCAN-as well as a postmortem autopsy dataset from the National Alzheimer's Coordinating Center (NACC; n = 3,188). All in vivo participants had tau-PET imaging, clinical diagnosis, and neurobehavioral assessments. Participants were assigned a biological Alzheimer's disease stage based on their tau-PET scan according to the Alzheimer's Association revised criteria stages. The autopsy dataset included individuals with moderate-to-frequent neuritic plaques (CERAD scores 2-3), along with premortem clinical and neurobehavioral data. Clinical-biological concordance was quantified using squared-weighted Cohen's Kappa. Ordinal and linear regression models assessed associations between biological stage and clinical severity (CDR-Sum of Boxes, MMSE), adjusting for age, sex, and cohort. Postmortem analyses evaluated the impact of comorbid neuropathologies on clinical-biological discordance using adjusted odds ratios and ordinal regression. Overall concordance between clinical and biological Alzheimer's disease staging was moderate (Cohen's Kappa=0.52, p < 0.001). Approximately 70% of individuals classified as cognitively unimpaired or with dementia exhibited biological stages consistent with their clinical diagnoses. In contrast, transitional decline and mild cognitive impairment (MCI) groups were more heterogenous. Notably, 25% of Aβ-positive individuals with MCI demonstrated no detectable tau-PET abnormality. Nonetheless, advanced tau-PET stage was reliably associated with clinical impairment. In the NACC autopsy dataset, nearly all individuals with more severe clinical stage than their proposed biological stage exhibited comorbid neuropathologies, including FTLD-TDP-43, FTLD-tau, Lewy bodies, LATE, and cerebrovascular disease. The number of comorbid pathologies was strongly associated with increased odds of clinical dementia (t = 8.45, p < 0.001). While there is moderate agreement between clinical and biological stages of Alzheimer's disease across the entire disease spectrum, strong agreement is found in clinically unimpaired and dementia stages. Comparison of clinical and biological Alzheimer's disease stages provides a framework for understanding the large contributions of non-AD neurodegenerative diseases to dementia in Aβ-positive individuals. Our results have important implications for clinical trial recruitment strategies and highlight the urgent need for biomarkers for non-AD pathological processes.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid41523185,

title = {Cortical asymmetry in autosomal dominant Alzheimer's disease progression},

author = {Agnès Pérez-Millan and Neus Falgàs and Beatriz Bosch and Sergi Borrego-Écija and Anna Antonell and Guadalupe Fernández-Villullas and Diana Esteller-Gauxax and Adrià Tort-Merino and Núria Bargalló and Mircea Balasa and Albert Lladó and David Aguillon and Patricio Chrem and Gregory S Day and Emma Devenney and Edward D Huey and Takeshi Ikeuchi and Mathias Jucker and Kensaku Kasuga and Jonathan Vöglein and Jee Hoon Roh and Paolo Vitali and Ana Luisa Sosa Ortiz and Jorge J Llibre-Guerra and Brian A Gordon and Eric McDade and Randall J Bateman and Raquel Sánchez-Valle and },

doi = {10.1093/braincomms/fcaf488},

issn = {2632-1297},

year  = {2026},

date = {2026-01-01},

journal = {Brain Commun},

volume = {8},

number = {1},

pages = {fcaf488},

abstract = {The cortical asymmetry index evaluates the cortical thickness asymmetry between hemispheres. We investigated cortical asymmetry index in asymptomatic and symptomatic mutation carriers of autosomal dominant Alzheimer's disease to explore the brain asymmetry within the Alzheimer's disease continuum. Sixty baseline T1-weighted MRI scans were obtained from the Clinic Barcelona cohort. Baseline and longitudinal MRI data from 564 participants within the dominantly inherited Alzheimer network observational study were used as an independent, confirmatory cohort. Cerebrospinal fluid and plasma neurofilament light chain levels were included when available. Cortical thickness was calculated using Freesurfer and cortical asymmetry index was calculated via an open-source pipeline. Cross-sectional analyses examined cortical asymmetry index differences based on clinical classification and  ε status, adjusting for age, sex and estimated years from onset, while correlations were assessed with age, estimated years from onset, mini-mental state examination scores, and neurofilament light. Longitudinal cortical asymmetry index evolution was modelled using generalized additive models in the dominantly inherited Alzheimer network observational study cohort, incorporating age, sex, and the interaction between group and estimated years from onset. The cortical asymmetry index successfully distinguished asymptomatic mutation carrier and symptomatic mutation carriers from healthy controls in the Clinic Barcelona cohort and symptomatic mutation carriers from controls in dominantly inherited Alzheimer network observational study. Higher cortical asymmetry index in mutation carriers (asymptomatic mutation carrier and symptomatic mutation carriers combined) and in symptomatic mutation carriers were associated with higher plasma neurofilament light levels, a closer proximity to symptom onset, and lower mini-mental state examination in the Clinic Barcelona cohort. In the dominantly inherited Alzheimer network observational study cohort, mutation carriers exhibited increased cortical asymmetry index compared to controls and correlated with elevated neurofilament light (plasma and Cerebrospinal fluid), lower mini-mental state examination, and a closer proximity to symptom onset.  carriers showed greater asymmetry than other  genotypes and significant cortical asymmetry index differences between asymptomatic mutation carrier and symptomatic mutation carriers. Longitudinally, cortical asymmetry index increased over time significantly in symptomatic mutation carriers. These findings underscore brain asymmetry as a potential biomarker for early Alzheimer's disease progression in autosomal dominant Alzheimer's disease, with implications for detection and monitoring tracking disease-related neuroanatomical changes.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid41433447,

title = {Alzheimer's Imaging Consortium},

author = {Stuart William Mitchell and Tevy Chan and Lydia Trudel and Seyyed Ali Hosseini and Arthur C Macedo and Marina P Gonçalves and Nesrine Rahmouni and Brandon J Hall and Kely Monica Quispialaya Socualaya and Joseph Therriault and Stijn Servaes and Gleb Bezgin and Yansheng Zheng and Etienne Aumont and Yi-Ting Wang and Jaime Fernandez Arias and Ana Paula Bernardes Real and Wan Lu Jia and Robert Hopewell and Chris Hsiao and Jean-Paul Soucy and Paolo Vitali and Tharick A Pascoal and Pedro Rosa-Neto},

doi = {10.1002/alz70862_109868},

issn = {1552-5279},

year  = {2025},

date = {2025-12-01},

journal = {Alzheimers Dement},

volume = {21 Suppl 8},

number = {Suppl 8},

pages = {e109868},

abstract = {BACKGROUND: Brain and cognitive resilience (BR, CR) reflect the capacity to maintain structural integrity and cognitive function despite pathological tau deposition in Alzheimer's disease (AD). Tau pathology can be characterized in terms of spatial extent of tauopathy (SEOT) or load using standardized uptake value ratio (SUVR). The aim was to compare SEOT and SUVR in their association with BR and CR. To replicate findings from Ossenkoppele et al. (2020) using MK-6240 PET imaging and evaluate demographic, genetic, and imaging factors associated with BR and CR. The objective of this study is to assess the value of SEOT metrics in resilience models and compare their predictive power to standardized uptake value ratio (SUVR) and to evaluate cross sectional interactions between tau pathology, cognitive resilience, and cognitive decline.nnMETHOD: We assessed 126 amyloid-β-positive participants TRIAD cohort with tau-PET using [F]MK6240 and cognitive assessments (MMSE). SEOT was quantified as the proportion of voxels considered as abnormal relative to young controls. We used Participants recruited from TRIAD cohort, including individuals with mild cognitive impairment (MCI) or AD, positive amyloid-β biomarkers, MK-6240 PET imaging data.nnRESULT: Higher Whole Cortex MK SUVR is associated with lower MMSE scores, showing increased tau pathology correlates with cognitive decline. MCI patients maintain higher MMSE scores despite some tau accumulation, while AD patients show greater variability and decline. The negative trend suggests tau deposition contributes to cognitive impairment, but other factors may also play a role. 2. Whole Cortex MK SUVR vs. MMSE the negative correlation between Whole Cortex SEOT and MMSE appears stronger, with a more pronounced decline in cognitive function (MMSE scores) as SEOT increases, suggesting SEOT may be a more sensitive marker of disease progression in AD patients.nnCONCLUSION: Whole Cortex SEOT exhibits a stronger negative correlation with MMSE compared to Whole Cortex MK-6240 SUVR, indicating that SEOT may serve as a more sensitive marker of cognitive decline in Alzheimer's disease and mild cognitive impairment. Further research is needed to validate SEOT's potential as a diagnostic or prognostic biomarker in neurodegenerative conditions.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid41266593,

title = {APOE ε4 potentiates tau related reactive astrogliosis assessed by cerebrospinal fluid YKL40 in Alzheimer's disease},

author = {Lydia Trudel and Joseph Therriault and Arthur C Macedo and Marcel S Woo and Nesrine Rahmouni and Étienne Aumont and Stijn Servaes and Seyyed Ali Hosseini and João Pedro Ferrari-Souza and Bruna Bellaver and Pamela L Ferreira and Tevy Chan and Yi-Ting Wang and Jaime Fernandez-Arias and Yansheng Zheng and Brandon Hall and Jenna Stevenson and Robert Hopewell and Chris Hung-Hsin Hsiao and Maxime Montembeault and Jesse Klostranec and Yasser Iturria-Medina and Paolo Vitali and Thomas K Karikari and Andrea L Benedet and Nicholas J Ashton and Eduardo Zimmer and Serge Gauthier and Tharick A Pascoal and Henrik Zetterberg and Kaj Blennow and Pedro Rosa-Neto},

doi = {10.1038/s43856-025-01171-4},

issn = {2730-664X},

year  = {2025},

date = {2025-11-01},

journal = {Commun Med (Lond)},

volume = {5},

number = {1},

pages = {484},

abstract = {BACKGROUND: Glial responses are involved in neurodegenerative processes, with tau pathology often associated with increased glial inflammatory responses in Alzheimer's disease (AD). The apolipoprotein E (APOE) ε4 allele, the major genetic susceptibility gene for AD, might contribute to this process by modulating both tau pathology and inflammatory cascades in the brain.nnMETHODS: We used data from the Translational Biomarkers of Alzheimer's Disease (TRIAD) cohort (n = 137) to investigate the association between YKL-40, a marker of reactive astrogliosis, and tau burden measured with PET imaging, while also exploring the involvement of APOE ε4 carriership. Statistical analyses included correlation and regression models controlling for age and sex.nnRESULTS: Here we show that tau pathology is positively associated with YKL-40 levels, reflecting regional patterns of astrocyte activity in the brain. Furthermore, this association is more widespread in individuals carrying the APOE ε4 allele, suggesting a genotype-specific modulation of the glial neuroinflammatory response.nnCONCLUSIONS: Our findings demonstrate a link between tau accumulation and astrocyte-mediated neuroinflammation in AD and highlight the modulatory role of APOE ε4 in this process. Taken together, our findings help inform the multifaceted role of tau-associated neuroinflammation in the progression of AD.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid41145530,

title = {Equivalence of the FCSRT and RAVLT to detect medial Temporal lobe atrophy and tauopathy},

author = {Etienne Aumont and Kelly Amiel and Delphine Oliva Lopez and Jaime Fernandez Arias and Maxime Montembeault and Gleb Bezgin and Brandon J Hall and Lydia Trudel and Tevy Chan and Nesrine Rahmouni and Jenna Stevenson and Stijn Servaes and Arthur C Macedo and Seyyed Ali Hosseini and Paolo Vitali and Nina Margherita Poltronetti and Jesse Klostranec and Joseph Therriault and Andréa L Benedet and Nicholas J Ashton and Henrik Zetterberg and Kaj Blennow and Thomas K Karikari and Gallen Triana-Baltzer and Hartmuth C Kolb and Serge Gauthier and Yasser Iturria-Medina and Pedro Rosa-Neto},

doi = {10.1038/s41598-025-21260-7},

issn = {2045-2322},

year  = {2025},

date = {2025-10-01},

journal = {Sci Rep},

volume = {15},

number = {1},

pages = {37425},

abstract = {In AD research, word-learning tests are often used interchangeably despite using distinct learning protocols. This study verified the equivalence of the Rey Auditory Learning Test (RAVLT) and Free and Cued Selective Reminding Test (FCSRT) when investigating medial temporal lobe (MTL) changes and AD-related tau pathology. We obtained the FCSRT and RAVLT immediate and delayed free recalls from 286 participants aged 51+. We segmented MTL regions to obtain the volume and tau-PET signal using the [F]MK-6240 tracer. Tau-PET Braak stages and plasma p-tau, p-tau and p-tau quantifications were also acquired. Using partial correlations, we compared FCSRT to RAVLT as well as their ability to detect the cognitive status the AD biomarker results. FCSRT and RAVLT were strongly correlated to one another (R > 0.779), with similar differentiation of cognitively impaired and cognitively unimpaired individuals (AUC > 0.810). Both predicted MTL volume, MTL tau-PET accumulation, plasma p-tau and Braak stages similarly, with no significant effect size differences. For all tests, a subtle memory impairment was found at tau-PET Braak stage III, while more robust impairments were found at stage IV onward. Despite their differences, both the RAVLT and FCSRT are equivalent at detecting AD-related pathology and symptoms, suggesting that, in these contexts, they may be used interchangeably. However, these results should be interpreted with care since the sample is not representative of a global population.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid40951978,

title = {Rates of clinical progression according to biological Alzheimer's disease stages},

author = {Lydia Trudel and Joseph Therriault and Arthur C Macedo and Stijn Servaes and Seyyed Ali Hosseini and Gleb Bezgin and Nesrine Rahmouni and Tevy Chan and Jaime Fernandez-Arias and Étienne Aumont and Yi-Ting Wang and Yansheng Zheng and Brandon Hall and Robert Hopewell and Chris Hung-Hsin Hsiao and Arthur W Toga and Meredith N Braskie and Karin L Meeker and Jean-Paul Soucy and Serge Gauthier and Paolo Vitali and Sid E O'Bryant and Tharick A Pascoal and Pedro Rosa-Neto},

doi = {10.1002/alz.70624},

issn = {1552-5279},

year  = {2025},

date = {2025-09-01},

journal = {Alzheimers Dement},

volume = {21},

number = {9},

pages = {e70624},

abstract = {INTRODUCTION: Predicting the rate of cognitive decline and the likelihood of progression to dementia remains a critical unmet need in clinical settings.nnMETHODS: We assessed progression to mild cognitive impairment (MCI) and all-cause dementia in 492 individuals from the TRIAD, ADNI, and HABS-HD cohorts followed for an average of 2.49 years. Amyloid-positive participants were staged according to the Alzheimer's Association biological staging framework (A+T-/A+T+/A+T+/A+T+).nnRESULTS: Cognitively unimpaired (CU) individuals in the A+T+, A+T+, and A+T+ biological Alzheimer's disease (AD) stages were at significantly higher risk of clinical progression compared to non-AD CU individuals. In individuals with MCI, advanced tau stage was associated with an 83% likelihood of developing dementia over 4 years. Biological AD staging demonstrated superior accuracy in predicting clinical progression compared to amyloid-PET (positron emission tomography) status, tau-PET status, and demographic information. All tau-PET-positive individuals showed a significantly faster rate of cognitive decline than non-AD controls, with the A+T+ stage showing the steepest rate of decline (p < 0.001).nnDISCUSSION: Our results highlight the prognostic value of biological AD staging.nnHIGHLIGHTS: Cognitively unimpaired (CU) individuals in all tau-PET (positron emission tomography)-positive biological Alzheimer's disease (AD) stages were at significantly higher risk of clinical progression compared to individuals without AD. In individuals with mild cognitive impairment (MCI), only the A+T+ stage reached a point where 50% of individuals had progressed to all-cause dementia, after 2.36 years. Biological AD staging demonstrated superior accuracy in predicting clinical progression to dementia compared to other PET biomarkers and demographic information. All tau-PET-positive individuals showed a significantly faster rate of cognitive decline than individuals without AD, with the A+T+ stage showing the steepest rate of decline.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid40346617,

title = {Plasma GFAP for populational enrichment of clinical trials in preclinical Alzheimer's disease},

author = {Bruna Bellaver and Guilherme Povala and Pamela C L Ferreira and Guilherme Bauer-Negrini and Firoza Z Lussier and Douglas T Leffa and João Pedro Ferrari-Souza and Matheus S Rodrigues and Livia Amaral and Markley S Oliveira and Carolina Soares and Andreia Rocha and Pampa Saha and Nesrine Rahmouni and Arthur Macedo and Cécile Tissot and Joseph Therriault and Stijn Servaes and Jesse Klostranec and Maxime Montembeault and Andréa L Benedet and Nicholas J Ashton and Rebecca Langhough Koscik and Tobey J Betthauser and Brad T Christian and Rachael Wilson and Gallen Triana-Baltzer and Paolo Vitali and Serge Gauthier and Henrik Zetterberg and Kaj Blennow and Thomas K Karikari and Dana Tudorascu and Eduardo R Zimmer and Sterling Johnson and Pedro Rosa-Neto and Tharick A Pascoal},

doi = {10.1002/alz.70209},

issn = {1552-5279},

year  = {2025},

date = {2025-05-01},

journal = {Alzheimers Dement},

volume = {21},

number = {5},

pages = {e70209},

abstract = {INTRODUCTION: Cognitively unimpaired (CU) amyloid beta (Aβ)+ individuals with elevated plasma glial fibrillary acidic protein (GFAP) have an increased risk of Alzheimer's disease (AD)-related progression. We tested the utility of plasma GFAP for population enrichment CU populations in clinical trials.nnMETHODS: We estimated longitudinal progression, effect size, and costs of hypothetical clinical trials designed to test an estimated 25% drug effect on reducing tau positron emission tomography (PET) accumulation in the medial temporal lobe (MTL) and temporal neocortical region (NEO-T).nnRESULTS: CU GFAP+/Aβ+ individuals present an increased annual rate of change and effect size in tau PET and tau PET compared to the other groups. An enrichment strategy selecting CU GFAP+/Aβ+ individuals would require a smaller sample size (≈ 57% reduction) and fewer Aβ PET scans (≈ 74% reduction) than trials enriched with Aβ PET alone, reducing total clinical trial costs by up to 64%.nnDISCUSSION: Our results suggest that clinical trials focusing on preclinical AD recruiting Aβ+ individuals with elevated GFAP levels would improve cost effectiveness.nnHIGHLIGHTS: Cognitively unimpaired (CU) glial fibrillary acidic protein (GFAP)+/amyloid beta (Aβ)+ shows increased changes in tau positron emission tomography (PET) . CU GFAP+/Aβ+ enriched clinical trials require a reduced sample size compared to Aβ+ only. CU GFAP+/Aβ+ enrichment reduces Aβ PET scans required and costs. CU GFAP+/Aβ+ enrichment allows the selection of individuals at early stages of the Alzheimer's disease continuum.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid39631245,

title = {Hippocampal atrophy over two years in relation to tau, amyloid-β and memory in older adults},

author = {Etienne Aumont and Marc-André Bedard and Aurélie Bussy and Jaime Fernandez Arias and Cecile Tissot and Brandon J Hall and Joseph Therriault and Nesrine Rahmouni and Jenna Stevenson and Stijn Servaes and Arthur C Macedo and Paolo Vitali and Nina Margherita Poltronetti and Olga Fliaguine and Lydia Trudel and Serge Gauthier and Mallar M Chakravarty and Pedro Rosa-Neto},

doi = {10.1016/j.neurobiolaging.2024.11.007},

issn = {1558-1497},

year  = {2025},

date = {2025-02-01},

journal = {Neurobiol Aging},

volume = {146},

pages = {48--57},

abstract = {In this longitudinal brain imaging study, we aimed to characterize hippocampal tau accumulation and subfield atrophy relative to cortical amyloid-β and memory performance. We measured tau-PET in regions associated with Braak stages I to VI, global amyloid-PET burden, hippocampal subfield volumes and memory assessments from 173 participants aged 55-85. Eighty-six of these participants were tested again two years later. Tau-PET change in the Braak II region, corresponding to the hippocampus and the entorhinal cortex, was significantly associated with the cornu ammonis 1 (CA1) atrophy and memory score. This CA1 atrophy did not significantly mediate the association between tau and memory, nor did global amyloid-PET burden correlate with tau-PET changes in the Braak II region. Longitudinal hippocampal tau accumulation is amyloid-β-independent and co-localized with subfield atrophy. As tau-associated memory decline seems to be independent from hippocampal atrophy, other mechanisms could contribute to the deficit.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid39972340,

title = {The impact of kidney function on Alzheimer's disease blood biomarkers: implications for predicting amyloid-β positivity},

author = {Burak Arslan and Wagner S Brum and Ilaria Pola and Joseph Therriault and Nesrine Rahmouni and Jenna Stevenson and Stijn Servaes and Kübra Tan and Paolo Vitali and Maxime Montembeault and Jesse Klostranec and Arthur C Macedo and Cecile Tissot and Serge Gauthier and Juan Lantero-Rodriguez and Eduardo R Zimmer and Kaj Blennow and Henrik Zetterberg and Pedro Rosa-Neto and Andrea L Benedet and Nicholas J Ashton},

doi = {10.1186/s13195-025-01692-z},

issn = {1758-9193},

year  = {2025},

date = {2025-02-01},

journal = {Alzheimers Res Ther},

volume = {17},

number = {1},

pages = {48},

abstract = {BACKGROUND: Impaired kidney function has a potential confounding effect on blood biomarker levels, including biomarkers for Alzheimer's disease (AD). Given the imminent use of certain blood biomarkers in the routine diagnostic work-up of patients with suspected AD, knowledge on the potential impact of comorbidities on the utility of blood biomarkers is important. We aimed to evaluate the association between kidney function, assessed through estimated glomerular filtration rate (eGFR) calculated from plasma creatinine and AD blood biomarkers, as well as their influence over predicting Aβ-positivity.nnMETHODS: We included 242 participants from the Translational Biomarkers in Aging and Dementia (TRIAD) cohort, comprising cognitively unimpaired individuals (CU; n = 124), mild cognitive impairment (MCI; n = 58), AD dementia (n = 34), and non-AD dementia (n = 26) patients all characterized by [F] AZD-4694. Plasma samples were analyzed for Aβ42, Aβ40, glial fibrillary acidic protein (GFAP), neurofilament light chain (NfL), tau phosphorylated at threonine 181 (p-tau181), 217 (p-tau217), 231 (p-tau231) and N-terminal containing tau fragments (NTA-tau) using Simoa technology. Kidney function was assessed by eGFR in mL/min/1.73 m, based on plasma creatinine levels, age, and sex. Participants were also stratified according to their eGFR-indexed stages of chronic kidney disease (CKD). We evaluated the association between eGFR and blood biomarker levels with linear models and assessed whether eGFR provided added predictive value to determine Aβ-positivity with logistic regression models.nnRESULTS: Biomarker concentrations were highest in individuals with CKD stage 3, followed by stages 2 and 1, but differences were only significant for NfL, Aβ42, and Aβ40 (not Aβ42/Aβ40). All investigated biomarkers showed significant associations with eGFR except plasma NTA-tau, with stronger relationships observed for Aβ40 and NfL. However, after adjusting for either age, sex or Aβ-PET SUVr, the association with eGFR was no longer significant for all biomarkers except Aβ40, Aβ42, NfL, and GFAP. When evaluating whether accounting for kidney function could lead to improved prediction of Aβ-positivity, we observed no improvements in model fit (Akaike Information Criterion, AIC) or in discriminative performance (AUC) by adding eGFR to a base model including each plasma biomarker, age, and sex. While covariates like age and sex improved model fit, eGFR contributed minimally, and there were no significant differences in clinical discrimination based on AUC values.nnCONCLUSIONS: We found that kidney function seems to be associated with AD blood biomarker concentrations. However, these associations did not remain significant after adjusting for age and sex, except for Aβ40, Aβ42, NfL, and GFAP. While covariates such as age and sex improved prediction of Aβ-positivity, including eGFR in the models did not lead to improved prediction for any biomarker. Our findings indicate that renal function, within the normal to mild impairment range, does not seem to have a clinically relevant impact when using highly accurate blood biomarkers, such as p-tau217, in a biomarker-supported diagnosis.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid39879633,

title = {Plasma phosphorylated tau217 strongly associates with memory deficits in the Alzheimer's disease spectrum},

author = {Jaime Fernández Arias and Wagner S Brum and Gemma Salvadó and Joseph Therriault and Stijn Servaes and Yi-Ting Wang and Etienne Aumont and Nesrine Rahmouni and Arthur Macedo and Kely Quispialaya and Seyyed Ali Hosseini and Peter Kunach and Wan Lu Jia and Tevy Chan and Lydia Trudel and Brandon Hall and Yanseng Zheng and Sejal Mohapatra and Sulantha S Mathotaarachchi and Paolo Vitali and Cécile Tissot and Gleb Bezgin and Yasser Iturria-Medina and Nicholas J Ashton and Andréa Lessa Benedet and Thomas K Karikari and Gallen Triana-Baltzer and Jesse Klostranec and Hartmuth C Kolb and Eduardo R Zimmer and Shorena Janelidze and Niklas Mattson-Carlgren and Erik Stomrud and Sebastian Palmqvist and Henrik Zetterberg and Kaj Blennow and Tharick Pascoal and Maxime Montembeault and Oskar Hansson and Pedro Rosa-Neto},

doi = {10.1093/brain/awaf033},

issn = {1460-2156},

year  = {2025},

date = {2025-01-01},

journal = {Brain},

abstract = {Plasma phosphorylated tau biomarkers open unprecedented opportunities for identifying carriers of Alzheimer's disease pathophysiology in early disease stages using minimally invasive techniques. Plasma p-tau biomarkers are believed to reflect tau phosphorylation and secretion. However, it remains unclear to what extent the magnitude of plasma p-tau abnormalities reflects neuronal network disturbance in the form of cognitive impairment. To address this question, we included 103 cognitively unimpaired elderly and 40 cognitively impaired, amyloid-β positive individuals from the TRIAD cohort, as well as 336 cognitively unimpaired and 216 cognitively impaired, amyloid-β positive older adults from the BioFINDER-2 cohort. Participants had tau PET scans, amyloid PET scans or amyloid CSF, p-tau217, p-tau181 and p-tau231 blood measures, structural T1-MRI and cognitive assessments. In this cross-sectional study, we used regression models and correlation analyses to assess the relationship between plasma biomarkers and cognitive scores. Furthermore, we applied receiver operating characteristic curves to assess cognitive impairment across plasma biomarkers. Finally, we categorized participants into amyloid (A), p-tau (T1), and tau PET (T2) positive (+) or negative (-) profiles and ran nonparametric comparisons to assess differences across cognitive domains. We found that plasma p-tau217 was more associated with cognitive performance than p-tau181 and p-tau231, and that this relationship was particularly strong for memory scores (TRIAD: βp-tau217=-0.53; βp-tau181=-0.35; βp-tau231=-0.24; BioFINDER-2: βp-tau217=-0.52; βp-tau181=-0.24; βp-tau231=-0.29). Associations in amyloid-β positive participants resembled these results, but other cognitive scores also showed strong associations in cognitively impaired individuals. Moreover, plasma p-tau217 outperformed plasma p-tau181 and plasma p-tau231 in identifying memory impairment (Area Under the Curve values for TRIAD: p-tau217=0.86, p-tau181=0.77, p-tau231=0.75; Area Under the Curve values for BioFINDER-2: p-tau217=0.86, p-tau181=0.76, p-tau231=0.81), and in identifying executive function impairment only in the BioFINDER-2 cohort (p-tau217=0.82, p-tau181=0.76, p-tau231=0.76). Lastly, we showed that subtle memory deficits were present in A+T1+T2- participants for plasma p-tau217 (p=0.007) and plasma p-tau181 (p=0.01) in the TRIAD cohort, and for all biomarkers across cognitive domains in A+T1-T2- and A+T1+T2- individuals (p<0.001 in all) in the BioFINDER-2 cohort. A+T1+T2+ individuals showed cognitive deficits in both cohorts (p<0.001 in all). Together, our results suggest that plasma p-tau217 stands out as a biomarker capable of identifying memory deficits due to Alzheimer's disease and that memory impairment certainly occurs in amyloid and plasma p-tau positive individuals that have no significant amounts of tau in the neocortex.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}