Cortical β-amyloid burden, gray matter, and memory in adults at varying APOE ε4 risk for Alzheimer's disease

NEUROBIOLOGY OF AGING

卷:61

Article

Mecca, Adam P.^1,2  Barcelos, Nicole M.^1,2  Wang, Shuo³  Bruck, Anna^1,2  Nabulsi, Nabeel³  Planeta-Wilson, Beata³  Nadelmann, Jennifer^1,2  Benincasa, Amanda L.^1,2  Ropchan, Jim³  Huang, Yiyun³  Gelernter, Joel^1,2,4  Van Ness, Peter H.^5,6  Carson, Richard E.³  van Dyck, Christopher H.^1,2,7,8 

[1] Yale Univ, Sch Med, Alzheimers Dis Res Unit, One Church St,8th Floor, New Haven, CT 06510 USA

[2] Yale Univ, Sch Med, Dept Psychiat, New Haven, CT 06510 USA

[3] Yale Univ, Sch Med, Dept Radiol & Biomed Imaging, New Haven, CT 06510 USA

[4] Vet Affairs Connecticut Healthcare Syst, West Haven, CT USA

[5] Yale Univ, Sch Med, Dept Internal Med, Geriatr Sect, New Haven, CT 06510 USA

[6] Yale Univ, Sch Med, Program Aging, New Haven, CT 06510 USA

[7] Yale Univ, Sch Med, Dept Neurosci, New Haven, CT 06510 USA

[8] Yale Univ, Sch Med, Dept Neurol, New Haven, CT 06510 USA

关键词: Amyloid-beta;    Apolipoprotein E;    Alzheimer's disease;    [C-11]PiB;    PET;    Preclinical Alzheimer's disease;   

DOI  :  10.1016/j.neurobiolaging.2017.09.027

来源: Elsevier

【 摘 要 】

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.

【 授权许可】

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