Cortical beta-amyloid burden, gray matter, and memory in adults at varying APOE epsilon 4 risk for Alzheimer's disease

: Mecca AP, Barcelos NM, Wang S, Bruck A, Nabulsi N, Planeta-Wilson B, Nadelmann J, Benincasa AL, Ropchan J, Huang YY, Gelernter J, Van Ness PH, Carson RE, van Dyck CH

Publisher: ELSEVIER SCIENCE INC

: 2018

: Neurobiology of Aging

: NEUROBIOLOGY OF AGING

: NEUROBIOL AGING

: 61

: 207

: 214

: 8

: 0197-4580

DOI: https://doi.org/10.1016/j.neurobiolaging.2017.09.027

Models of preclinical Alzheimer's disease (AD) propose that cerebral amyloidosis leads to neuro-degeneration and subsequent cognitive decline. This study investigated whether APOE genotype is related to beta-amyloid (A beta) burden in brain regions preferentially affected by AD and whether A beta burden is associated with gray-matter (GM) fraction (as a marker of neurodegeneration) and episodic memory performance in cognitively normal middle-aged individuals at varying genetic risk for AD. Three groups of cognitively normal participants aged 50-65 years with a first-degree family history of AD (APOE genotype epsilon 4 epsilon 4 [n = 15], epsilon 3 epsilon 4 [n = 15], and epsilon 3 epsilon 3 [n = 15]) underwent [C-11]PiB positron emission tomography scans to quantify cortical A beta, brain magnetic resonance imaging, and neuropsychological testing. APOE epsilon 4 epsilon 4 participants demonstrated significantly higher cortical A beta burden than APOE epsilon 3 epsilon 3 (p < 0.001). Furthermore, cortical A beta burden was inversely associated with cortical GM fraction (p = 0.017) but not episodic memory performance. In cognitively normal, middle-aged individuals, A beta burden is significantly associated with GM fraction but not episodic memory performance. These findings are consistent with models of preclinical AD in which neurodegeneration occurs before manifest cognitive decline. (C) 2017 The Authors. Published by Elsevier Inc.