Relationship of amyloid beta and neurofibrillary tau deposition in Neurodegeneration in Aging Down Syndrome (NiAD) study at baseline
Importance: Adults with Down syndrome (DS) are at high-risk of revealing Alzheimer's disease (AD) pathology, in part due to the triplication of chromosome 21 encoding the amyloid precursor protein. Adults with DS are uniformly affected by AD pathology by their 30′s and have a 70% to 80% chance of clinical dementia by their 60′s. Our previous studies have assessed longitudinal changes in amyloid beta (Aβ) accumulation in DS. Objective: The goal of the present study was to assess the presence of brain tau using [18F]AV-1451 positron emission tomography (PET) in DS and to assess the relationship of brain tau pathology to Aβ using Pittsburgh Compound B (PiB)-PET. Design: Cohort study. Setting: Multi-center study. Participants: Participants consisted of a sample of individuals with DS and sibling controls recruited from the community; exclusion criteria included contraindications for magnetic resonance imaging (MRI) and/or a medical or psychiatric condition that impaired cognitive functioning. Exposures: PET brain scans to assess Aβ ([11C]PiB) and tau ([18F]AV-1451) burden. Main outcomes and measures: Multiple linear regression models (adjusted for chronological age, sex and performance site) were used to examine associations between regional [18F]AV-1451 standard uptake value ratio (SUVR) (based on regions associated with Braak stages 1-6) and global [11C]PiB SUVR (as both a continuous and dichotomous variable). Results: A cohort of 156 participants (mean age = 39.05, SD(8.4)) were examined. These results revealed a significant relationship between in vivo Aβ and tau pathology in DS. As a dichotomous variable, [18F]AV-1451 retention was higher in each Braak region in PiB(+) participants. We also found, based on our statistical models, starting with the Braak 3 region of interest (ROI), an acceleration of [18F]AV-1451 SUVR deposition with [11C]PiB SUVR increases.
Alzheimer's and Dementia: Translational Research and Clinical Interventions
Digital Object Identifier (DOI)
Tudorascu, D. L.; Laymon, C. M.; Zammit, M.; Minhas, D. S.; Anderson, S. J.; Ellison, P. A.; Zaman, S.; Ances, B. M.; Sabbagh, M.; Johnson, S. C.; Mathis, C. A.; Klunk, W. E.; Handen, B. L.; Christian, B. T.; and Cohen, A. D., "Relationship of amyloid beta and neurofibrillary tau deposition in Neurodegeneration in Aging Down Syndrome (NiAD) study at baseline" (2020). Neurology. 1020.