title: Lack of neural compensatory mechanisms of BDNF val66met met carriers and APOE E4 carriers in healthy aging, mild cognitive impairment, and Alzheimer's disease.
abstract: 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.
authors.affiliation: The Litwin-Zucker Alzheimer's Disease Research Center, The Feinstein Institute for Medical Research, Manhasset, NY, USA; FIDMAG Hermanas Hospitalarias Research Foundation & CIBERSAM, Sant Boi de Llobregat, Spain.
authors.forename: Jesus J
authors.initials: JJ
authors.lastname: Gomar
authors.affiliation: The Litwin-Zucker Alzheimer's Disease Research Center, The Feinstein Institute for Medical Research, Manhasset, NY, USA.
authors.forename: Concepcion
authors.initials: C
authors.lastname: Conejero-Goldberg
authors.affiliation: Taub Institute for Research on Alzheimer's disease and the Aging Brain, The Gertrude H. Sergievsky Center, Columbia University, New York, NY, USA; College of Physicians and Surgeons, Columbia University, New York, NY, USA.
authors.forename: Edward D
authors.initials: ED
authors.lastname: Huey
authors.affiliation: The Litwin-Zucker Alzheimer's Disease Research Center, The Feinstein Institute for Medical Research, Manhasset, NY, USA; Hofstra North Shore LIJ School of Medicine, Hempstead, NY, USA.
authors.forename: Peter
authors.initials: P
authors.lastname: Davies
authors.affiliation: The Litwin-Zucker Alzheimer's Disease Research Center, The Feinstein Institute for Medical Research, Manhasset, NY, USA; Hofstra North Shore LIJ School of Medicine, Hempstead, NY, USA. Electronic address: tgoldber@nshs.edu.
authors.forename: Terry E
authors.initials: TE
authors.lastname: Goldberg
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000375:Aging; D000544:Alzheimer Disease / Q000235:genetics* / Q000473:pathology / Q000523:psychology; D001057:Apolipoproteins E / Q000235:genetics*; D001921:Brain / Q000473:pathology*; D019208:Brain-Derived Neurotrophic Factor / Q000235:genetics*; D003071:Cognition; D060825:Cognitive Dysfunction / Q000235:genetics* / Q000473:pathology / Q000523:psychology; D015331:Cohort Studies; D005260:Female; D005838:Genotype; D006579:Heterozygote; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D061212:Memory, Episodic; D008875:Middle Aged; D059906:Neuroimaging; D011110:Polymorphism, Genetic
chemical_list: D001057:Apolipoproteins E; D019208:Brain-Derived Neurotrophic Factor; C579455:BDNF protein, human
keywords: AD; APOE; Aging; BDNF; Brain morphometry; Cognition; MCI