Ontology highlight
ABSTRACT: Background
Neuroimaging studies of autosomal dominant Alzheimer's disease (ADAD) enable characterization of the trajectories of cerebral amyloid-? (A?) and tau accumulation in the decades prior to clinical symptom onset. Longitudinal rates of regional tau accumulation measured with positron emission tomography (PET) and their relationship with other biomarker and cognitive changes remain to be fully characterized in ADAD.Methods
Fourteen ADAD mutation carriers (Presenilin-1 E280A) and 15 age-matched non-carriers from the Colombian kindred underwent 2-3 sessions of A? (11C-Pittsburgh compound B) and tau (18F-flortaucipir) PET, structural magnetic resonance imaging, and neuropsychological evaluation over a 2-4-year follow-up period. Annualized rates of change for imaging and cognitive variables were compared between carriers and non-carriers, and relationships among baseline measurements and rates of change were assessed within carriers.Results
Longitudinal measurements were consistent with a sequence of ADAD-related changes beginning with A? accumulation (16?years prior to expected symptom onset, EYO), followed by entorhinal cortex (EC) tau (9 EYO), neocortical tau (6 EYO), hippocampal atrophy (6 EYO), and cognitive decline (4 EYO). Rates of tau accumulation among carriers were most rapid in parietal neocortex (~?9%/year). EC tau PET signal at baseline was a significant predictor of subsequent neocortical tau accumulation and cognitive decline within carriers.Conclusions
Our results are consistent with the sequence of biological changes in ADAD implied by cross-sectional studies and highlight the importance of EC tau as an early biomarker and a potential link between A? burden and neocortical tau accumulation in ADAD.
SUBMITTER: Sanchez JS
PROVIDER: S-EPMC7811244 | biostudies-literature | 2021 Jan
REPOSITORIES: biostudies-literature
Alzheimer's research & therapy 20210115 1
<h4>Background</h4>Neuroimaging studies of autosomal dominant Alzheimer's disease (ADAD) enable characterization of the trajectories of cerebral amyloid-β (Aβ) and tau accumulation in the decades prior to clinical symptom onset. Longitudinal rates of regional tau accumulation measured with positron emission tomography (PET) and their relationship with other biomarker and cognitive changes remain to be fully characterized in ADAD.<h4>Methods</h4>Fourteen ADAD mutation carriers (Presenilin-1 E280A ...[more]