Lack of neural compensatory mechanisms of BDNF val66met met carriers and APOE E4 carriers in healthy aging, mild cognitive impairment, and Alzheimer's disease

NEUROBIOLOGY OF AGING

卷:39

Article

Gomar, Jesus J.^1,2,3  Conejero-Goldberg, Concepcion¹  Huey, Edward D.^4,5  Davies, Peter^1,6  Goldberg, Terry E.^1,6 

[1] Feinstein Inst Med Res, Litwin Zucker Alzheimers Dis Res Ctr, Manhasset, NY USA

[2] FIDMAG Hermanas Hosp Res Fdn, St Boi De Llobregat, Spain

[3] CIBERSAM, St Boi De Llobregat, Spain

[4] Columbia Univ, Taub Inst Res Alzheimers Dis & Aging Brain, Gertrude H Sergievsky Ctr, New York, NY USA

[5] Columbia Univ, Coll Phys & Surg, New York, NY USA

[6] Hofstra North Shore LIJ Sch Med, Hempstead, NY USA

关键词: BDNF;    APOE;    Aging;    MCI;    AD;    Brain morphometry;    Cognition;   

DOI  :  10.1016/j.neurobiolaging.2015.12.004

来源: Elsevier

【 摘 要 】

Compromises in compensatory neurobiologic mechanisms due to aging and/or genetic factors (i.e., APOE gene) may influence brain-derived neurotrophic factor (BDNF) val66met polymorphism effects on temporal lobe morphometry and memory performance. We studied 2 cohorts from Alzheimer's Disease Neuroimaging Initiative: 175 healthy subjects and 222 with prodromal and established Alzheimer's disease. Yearly structural magnetic resonance imaging and cognitive performance assessments were carried out over 3 years of follow-up. Both cohorts had similar BDNF Val/Val and Met allele carriers' (including both Val/Met and Met/Met individuals) distribution. In healthy subjects, a significant trend for thinner posterior cingulate and precuneus cortices was detected in Met carriers compared to Val homozygotes in APOE E4 carriers, with large and medium effect sizes, respectively. The mild cognitive impairment/Alzheimer's disease cohort showed a longitudinal decline in entorhinal thickness in BDNF Met carriers compared to Val/Val in APOE E4 carriers, with effect sizes ranging from medium to large. In addition, an effect of BDNF genotype was found in APOE E4 carriers for episodic memory (logical memory and ADAS-Cog) and semantic fluency measures, with Met carriers performing worse in all cases. These findings suggest a lack of compensatory mechanisms in BDNF Met carriers and APOE E4 carriers in healthy and pathological aging. (C) 2016 Elsevier Inc. All rights reserved.

【 授权许可】

Free