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Amirah Anderson
Pronouns
She/Her/Hers
Job Title
Technical research assistant II
Academic Rank
Department
Neurology
Authors
Amirah K. Anderson,1 Andrew M. Stern,1 Beth Ostaszewski,1 Yuqi Cai, 1 Lei Liu, 1 Kathryn L. Van Pelt, 2 Dennis J. Selkoe,1* Frederick Schmitt,2 Elizabeth Head,3 and the Alzheimer’s Biomarker Consortium – Down Syndrome (ABC-DS) investigators
Principal Investigator
Dennis Selkoe, MD
Research Category: Neurosciences
Tags
New blood-based biomarkers may serve as a more reliable and practical method to identify patients with or at risk for AD and understand pathobiology when imaging or CSF acquisition is difficult. Individuals with Down Syndrome are at similar high risk of developing AD pathology as carriers of autosomal dominant point mutations in the Amyloid-β pathway. Ultrasensitive plasma immunoassays for tau N-terminal fragment (NT1-tau) and Aβ isoforms predict cognitive decline and pathology. Plasma NT1-tau and oAβ levels were measured in an observational cohort (N=213) and showed correlation with cerebral spinal fluid samples sent for BWH clinic approved AD biomarker testing (ADmark and ADEVL). Plasma NT1-tau, Aβ37, Aβ40, and Aβ42 levels were measured in a longitudinal discovery cohort (N = 85 participants, 220 samples) to predict AD in a cross-sectional validation cohort (N = 297). Linear mixed models assessed change in the discovery cohort over time, with covariates including baseline age, sex, level of intellectual disability, consensus diagnosis, and performance on the Dementia Scale for People with Learning Disabilities. NT1-tau correlates with age and declining cognitive performance among people with DS. Further validation of NT1-tau and other plasma biomarkers of AD pathology in large, heterogeneous DS cohorts is important for clinical utility.
New blood-based biomarkers may serve as a more reliable and practical method to identify patients with or at risk for AD and understand biology when imaging or cerebral spinal fluid (CSF) acquisition is difficult. Individuals with Down Syndrome are at similar high risk of developing AD pathology as carriers of mutations in the Amyloid-β pathway. Ultrasensitive blood tests to measure the amount of tau N-terminal fragment (NT1-tau) and Aβ proteins could predict cognitive decline and AD pathology. Plasma NT1-tau, Aβ37, Aβ40, Aβ42, oAβ levels were measured in an observational cohort (N=213), longitudinal discovery cohort (N = 85 participants, 220 samples) and a cross-sectional validation cohort (N = 297). CSF samples in the observational cohort were sent for BWH clinic approved AD biomarker testing (ADmark and ADEVL) and analyzed against NT1 and oAB assays. Statistical models assessed change in levels in the discovery cohort over time, with covariates including baseline age, sex, level of intellectual disability, consensus diagnosis, and performance on the Dementia Scale for People with Learning Disabilities. NT1-tau correlates with age and worse cognitive performance among people with DS. Further validation of NT1-tau and other plasma biomarkers of AD pathology in large DS cohorts is important for clinical utility.
