Mitochondrial complex I abnormalities is associated with tau and clinical symptoms in mild Alzheimer's disease.
|Title||Mitochondrial complex I abnormalities is associated with tau and clinical symptoms in mild Alzheimer's disease.|
|Publication Type||Journal Article|
|Year of Publication||2021|
|Authors||Terada T, Therriault J, Kang MSu Peter, Savard M, Pascoal TAli, Lussier F, Tissot C, Wang Y-T, Benedet A, Matsudaira T, Bunai T, Obi T, Tsukada H, Ouchi Y, Rosa-Neto P|
|Date Published||2021 04 26|
|Keywords||Aged, Aged, 80 and over, Alzheimer Disease, Aminopyridines, Aniline Compounds, Benzothiazoles, Brain Chemistry, Carbon Radioisotopes, Electron Transport Complex I, Entorhinal Cortex, Female, Fluorine Radioisotopes, Humans, Magnetic Resonance Imaging, Male, Mental Status and Dementia Tests, Middle Aged, Neuroimaging, Positron-Emission Tomography, Pyridazines, Pyridines, Radiopharmaceuticals, Severity of Illness Index, Symptom Assessment, tau Proteins, Thiazoles|
BACKGROUND: Mitochondrial electron transport chain abnormalities have been reported in postmortem pathological specimens of Alzheimer's disease (AD). However, it remains unclear how amyloid and tau are associated with mitochondrial dysfunction in vivo. The purpose of this study is to assess the local relationships between mitochondrial dysfunction and AD pathophysiology in mild AD using the novel mitochondrial complex I PET imaging agent [F]BCPP-EF.METHODS: Thirty-two amyloid and tau positive mild stage AD dementia patients (mean age ± SD: 71.1 ± 8.3 years) underwent a series of PET measurements with [F]BCPP-EF mitochondrial function, [C]PBB3 for tau deposition, and [C] PiB for amyloid deposition. Age-matched normal control subjects were also recruited. Inter and intrasubject comparisons of levels of mitochondrial complex I activity, amyloid and tau deposition were performed.RESULTS: The [F]BCPP-EF uptake was significantly lower in the medial temporal area, highlighting the importance of the mitochondrial involvement in AD pathology. [C]PBB3 uptake was greater in the temporo-parietal regions in AD. Region of interest analysis in the Braak stage I-II region showed significant negative correlation between [F]BCPP-EF SUVR and [C]PBB3 BP (R = 0.2679, p = 0.04), but not [C] PiB SUVR.CONCLUSIONS: Our results indicated that mitochondrial complex I is closely associated with tau load evaluated by [C]PBB3, which might suffer in the presence of its off-target binding. The absence of association between mitochondrial complex I dysfunction with amyloid load suggests that mitochondrial dysfunction in the trans-entorhinal and entorhinal region is a reflection of neuronal injury occurring in the brain of mild AD.
|Alternate Journal||Mol Neurodegener|
|PubMed Central ID||PMC8074456|