Amyloid-dependent and amyloid-independent effects of Tau in individuals without dementia.
Joseph Therriault,Joseph Therriault,Tharick A. Pascoal,Tharick A. Pascoal,Marcus Sefranek,Sulantha Mathotaarachchi,Andrea Lessa Benedet,Andrea Lessa Benedet,Mira Chamoun,Mira Chamoun,Firoza Z. Lussier,Firoza Z. Lussier,Cecile Tissot,Cecile Tissot,Bruna Bellaver,Pamela C.L. Ferreira,Eduardo R. Zimmer,Paramita Saha-Chaudhuri,Serge Gauthier,Serge Gauthier,Pedro Rosa-Neto +20 more
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TLDR
The authors investigated the relationship between the topography of amyloid-β plaques, tau neurofibrillary tangles, and the overlap between the two, with cognitive dysfunction in individuals without dementia.Abstract:
OBJECTIVE To investigate the relationship between the topography of amyloid-β plaques, tau neurofibrillary tangles, and the overlap between the two, with cognitive dysfunction in individuals without dementia. METHODS We evaluated 154 individuals who were assessed with amyloid-β PET with [18 F]AZD4694, tau-PET with [18 F]MK6240, structural MRI, and neuropsychological testing. We also evaluated an independent cohort of 240 individuals who were assessed with amyloid-β PET with [18 F]Florbetapir, tau-PET with [18 F]Flortaucipir, structural MRI, and neuropsychological testing. Using the VoxelStats toolbox, we conducted voxel-wise linear regressions between amyloid-PET, tau-PET, and their interaction with cognitive function, correcting for age, sex, and years of education. RESULTS In both cohorts, we observed that tau-PET standardized uptake value ratio in medial temporal lobes was associated with clinical dementia rating Sum of Boxes (CDR-SoB) scores independently of local amyloid-PET uptake (FWE corrected at p < 0.001). We also observed in both cohorts that in regions of the neocortex, associations between neocortical tau-PET and clinical function were dependent on local amyloid-PET (FWE corrected at p < 0.001). INTERPRETATION In medial temporal brain regions, characterized by the accumulation of tau pathology in the absence of amyloid-β, tau had direct associations with cognitive dysfunction. In brain regions characterized by the accumulation of both amyloid-β and tau pathologies such as the posterior cingulate and medial frontal cortices, tau's relationship with cognitive dysfunction was dependent on local amyloid-β concentrations. Our results provide evidence that amyloid-β in Alzheimer's disease influences cognition by potentiating the deleterious effects of tau pathology.read more
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Staging of Alzheimer's disease: past, present, and future perspectives.
Joseph Therriault,Eduardo R. Zimmer,Andrea Lessa Benedet,Tharick A. Pascoal,Serge Gauthier,Pedro Rosa-Neto +5 more
TL;DR: In this paper , the authors discuss the use of clinical and biomarker information in past, present, and future staging of AD. They highlight potential applications of PET, CSF, and plasma biomarkers for staging AD severity in vivo.
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Detection of Tau-PET Positivity in Clinically Diagnosed Mild Cognitive Impairment with Multidimensional Features
TL;DR: In this article , the authors used stepwise regression to select the unitary or combination of variables that best predicted tau-PET status in mild cognitive impairment (MCI) patients.
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Validity of serum neurofilament light chain as a prognostic biomarker of disease activity in multiple sclerosis
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Detection of tau-PET positivity in clinically diagnosed mild cognitive impairment with multidimensional features.
TL;DR: In this paper , the authors used stepwise regression to select the unitary or combination of variables that best predicted tau positron emission tomography (tau-PET) or cerebrospinal fluid analysis.
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