Genetic Risk for Alzheimer Disease and Plasma Tau Are Associated With Accelerated Parietal Cortex Thickness Change in Middle-Aged Adults.

Neurol Genet

Department of Psychology (J.P.H., K.V.), The Ohio State University, & Chronic Brain Injury Program, The Ohio State University, Columbus; Translational Research Center for TBI and Stress Disorders (TRACTS) (M.E.P., E.B., D.S., J.C., W.M., R.M.), VA Boston Healthcare System, MA; Department of Psychiatry (M.E.P., M.W.L., M.W.M., B.R.H.), Boston University School of Medicine, MA; Neuroimaging Research for Veterans (NeRVe) Center (E.B., D.S., J.C., W.M., R.M.), VA Boston Healthcare System, MA; Brain Aging and Dementia (BAnD) Laboratory (D.S.), A. A. Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital, Charlestown; National Center for PTSD (M.W.L., M.W.M., B.R.H.), Behavioral Sciences Division, VA Boston Healthcare System, MA; Boston University School of Medicine (M.W.L., R.S.), Biomedical Genetics, MA; Boston University School of Public Health (M.W.L.), Department of Biostatistics, MA; Department of Neurology (B.R.H.), Boston University School of Medicine, MA; Geriatric Research (W.M., R.M.), Education, and Clinical Center (GRECC), VA Boston Healthcare System, MA; and Department of Psychiatry (W.M., R.M.), Harvard Medical School, Boston, MA.

Published: February 2023

Background And Objectives: Neuroimaging and biomarker studies in Alzheimer disease (AD) have shown well-characterized patterns of cortical thinning and altered biomarker concentrations of tau and β-amyloid (Aβ). However, earlier identification of AD has great potential to advance clinical care and determine candidates for drug trials. The extent to which AD risk markers relate to cortical thinning patterns in midlife is unknown. The first objective of this study was to examine cortical thickness change associated with genetic risk for AD among middle-aged military veterans. The second objective was to determine the relationship between plasma tau and Aβ and change in brain cortical thickness among veterans stratified by genetic risk for AD.

Methods: Participants consisted of post-9/11 veterans (N = 155) who were consecutively enrolled in the Translational Research Center for TBI and Stress Disorders prospective longitudinal cohort and were assessed for mild traumatic brain injury (TBI) and posttraumatic disorder (PTSD). Genome-wide polygenic risk scores (PRSs) for AD were calculated using summary results from the International Genomics of Alzheimer's Disease Project. T-tau and Aβ40 and Aβ42 plasma assays were run using Simoa technology. Whole-brain MRI cortical thickness change estimates were obtained using the longitudinal stream of FreeSurfer. Follow-up moderation analyses examined the AD PRS × plasma interaction on change in cortical thickness in AD-vulnerable regions.

Results: Higher AD PRS, signifying greater genetic risk for AD, was associated with accelerated cortical thickness change in a right hemisphere inferior parietal cortex cluster that included the supramarginal gyrus, angular gyrus, and intraparietal sulcus. Higher tau, but not Aβ42/40 ratio, was associated with greater cortical thickness change among those with higher AD PRS. Mild TBI and PTSD were not associated with cortical thickness change.

Discussion: Plasma tau, particularly when combined with genetic stratification for AD risk, can be a useful indicator of brain change in midlife. Accelerated inferior parietal cortex changes in midlife may be an important factor to consider as a marker of AD-related brain alterations.

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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9893442PMC
http://dx.doi.org/10.1212/NXG.0000000000200053DOI Listing

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