Effect of apolipoprotein E4 on clinical, neuroimaging, and biomarker measures in noncarrier participants in the Dominantly Inherited Alzheimer Network

NEUROBIOLOGY OF AGING

卷:75

Article

Bussy, Aurelie^1,2,6  Snider, B. Joy^1,2  Coble, Dean^1,3  Xiong, Chengjie^1,3  Fagan, Anne M.^1,2  Cruchaga, Carlos^1,4  Benzinger, Tammie L. S.^1,5  Gordon, Brian A.^1,5  Hassenstab, Jason^1,2  Bateman, Randall J.^1,2  Morris, John C.^1,2 

[1] Washington Univ, Sch Med, Knight Alzheimer Dis Res Ctr, St Louis, MO 63110 USA

[2] Washington Univ, Sch Med, Dept Neurol, Campus Box 8111,660 S Euclid, St Louis, MO 63110 USA

[3] Washington Univ, Sch Med, Div Biostat, St Louis, MO 63110 USA

[4] Washington Univ, Sch Med, Dept Psychiat, St Louis, MO 63110 USA

[5] Washington Univ, Sch Med, Dept Radiol, St Louis, MO 63110 USA

[6] McGill Univ, Douglas Mental Hlth Univ Inst, Montreal, PQ, Canada

关键词: Alzheimer disease;    APOE;    Autosomal dominant;    Amyloid precursor protein;    Presenilin 1;    Presenilin 2;    Biomarkers;   

DOI  :  10.1016/j.neurobiolaging.2018.10.011

来源: Elsevier

【 摘 要 】

The apolipoprotein E epsilon 4 allele (APOE4) is the major genetic risk factor for sporadic Alzheimer's disease (AD). APOE4 may have effects on cognition and brain atrophy years before the onset of symptomatic AD. We analyzed the effects of APOE4 in a unique cohort of young adults who had undergone comprehensive assessments as part of the Dominantly Inherited Alzheimer Network (DIAN), an international longitudinal study of individuals from families with autosomal dominant AD. We analyzed the effect of an APOE4 allele on cognitive measures, volumetric MRI, amyloid deposition, glucose metabolism, and on cerebrospinal fluid levels of AD biomarkers in 162 participants that did not carry the mutant gene (noncarriers). APOE4+ and APOE4- mutation noncarriers had similar performance on cognitive measures. Amyloid deposition began at an earlier age in APOE4+ participants, whereas hippocampal volume was similar between the groups. These preliminary findings are consistent with growing evidence that the APOE4 allele may exert effects in midlife years before symptom onset, promoting amyloid deposition before altering cognitive performance or brain structure. (C) 2019 Elsevier Inc. All rights reserved.

【 授权许可】

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