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Comparative Study
. 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

Joshua Matyi  1 , JoAnn T Tschanz  1   2 , Gail B Rattinger  3 , Chelsea Sanders  1 , Elizabeth K Vernon  1 , Chris Corcoran  4 , John S K Kauwe  5 , Mona Buhusi  1
Affiliations
Comparative Study

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

Joshua Matyi et al. J Gerontol A Biol Sci Med Sci. .

Erratum in

Abstract

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.

Keywords: Brain-derived neurotrophic factor; Nerve growth factor; Single-nucleotide polymorphisms.

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Figures

Figure 1.
Figure 1.
Flow chart of final sample for analysis. Participants included in analyses (n = 3499) with data on one or more SNPs: AD or noncase as determined in Waves 2 through 4 of the CCSMA. Gray boxes represent subjects excluded from analyses at each level. AD = Alzheimer’s disease; CCSMA = Cache County Study on Memory in Aging; SNP = single-nucleotide polymorphism.
Figure 2.
Figure 2.
Survival function for rs2072446 from Cox regression models for males and females. Note that the plots for males and females who are not carriers of the minor (T) allele show nearly identical survival curves. Female carriers of the minor T allele have a significantly higher hazard and shortened survival duration for AD. AD = Alzheimer’s disease.
Figure 3.
Figure 3.
Survival function for rs56164415 from Cox regression models for males and females. Female carriers of the minor T allele have a significantly higher hazard and shortened survival duration for AD. AD = Alzheimer’s disease.
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