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J Gerontol A Biol Sci Med Sci. 2017 Nov 9;72(12):1607-1613. doi: 10.1093/gerona/glx092.

Sex Differences in Risk for Alzheimer's Disease Related to Neurotrophin Gene Polymorphisms: The Cache County Memory Study.

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Department of Psychology, Utah State University.
Center for Epidemiologic Studies, Utah State University.
Department of health Outcomes and Administrative Sciences, School of Pharmacy and Pharmaceutical Sciences, Binghamton University, New York.
Department of Mathematics and Statistics, Utah State University.
Department of Biology, Brigham Young University, Provo, Utah.


Neurotrophins, including nerve-growth factor and brain-derived neurotrophic factor, have been implicated in Alzheimer's disease (AD). Associations between AD and neurotrophin signaling genes have been inconsistent, with few studies examining sex differences in risk. We examined four single-nucleotide polymorphisms (SNPs) involved in neurotrophin signaling (rs6265, rs56164415, rs2289656, rs2072446) and risk for AD by sex in a population-based sample of older adults. Three thousand four hundred and ninety-nine individuals without dementia at baseline [mean (standard deviation) age = 74.64 (6.84), 58% female] underwent dementia screening and assessment over four triennial waves. Cox regression was used to examine time to AD or right censoring for each SNP. Female carriers of the minor T allele for rs2072446 and rs56164415 had a 60% (hazard ratio [HR] = 1.60, 95% confidence interval [CI] = 1.02-2.51) and 93% (HR = 1.93, 95% CI = 1.30-2.84) higher hazard for AD, respectively, than male noncarriers of the T allele. Furthermore, male carriers of the T allele of rs2072446 had a 61% lower hazard (HR = 0.39, 95% CI = 0.14-1.06) than male noncarriers at trend-level significance (p = .07). The association between certain neurotrophin gene polymorphisms and AD differs by sex and may explain inconsistent findings in the literature.


Brain-derived neurotrophic factor; Nerve growth factor; Single-nucleotide polymorphisms

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