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Effect of APOE ?4 allele on survival and fertility in an adverse environment.

ABSTRACT: The apolipoprotein-?4 allele (APOE-?4) is strongly associated with detrimental outcomes in affluent populations including atherosclerotic disease, Alzheimer's disease, and reduced lifespan. Despite these detrimental outcomes, population frequencies of APOE-?4 are high. We hypothesize that the high frequency of APOE-?4 was maintained because of beneficial effects during evolution when infectious pathogens were more prevalent and a major cause of mortality. We examined a rural Ghanaian population with a high pathogen exposure for selective advantages of APOE-?4, to survival and or fertility.This rural Ghanaian population (n = 4311) has high levels of mortality from widespread infectious diseases which are the main cause of death. We examined whether APOE-?4 was associated with survival (total follow-up time was 30,262 years) and fertility after stratifying by exposure to high or low pathogen levels. Households drawing water from open wells and rivers were classified as exposed to high pathogen levels while low pathogen exposure was classified as those drawing water from borehole wells. We found a non-significant, but positive survival benefit, i.e. the hazard ratio per APOE-?4 allele was 0.80 (95% confidence interval: 0.69 to 1.05), adjusted for sex, tribe, and socioeconomic status. Among women aged 40 years and older (n = 842), APOE-?4 was not associated with the lifetime number of children. However, APOE-?4 was associated with higher fertility in women exposed to high pathogen levels. Compared with women not carrying an APOE-?4 allele, those carrying one APOE-?4 allele had on average one more child and those carrying two APOE-?4 alleles had 3.5 more children (p = 0.018).Contrary to affluent modern-day populations, APOE-?4 did not carry a survival disadvantage in this rural Ghanaian population. Moreover, APOE-?4 promotes fertility in highly infectious environments. Our findings suggest that APOE-?4 may be considered as evolutionarily adaptive. Its adverse associations in affluent modern populations with later onset diseases of aging further characterize APOE-?4 as an example of antagonistic pleiotropy.

SUBMITTER: van Exel E

PROVIDER: S-EPMC5500260 | biostudies-literature | 2017

REPOSITORIES: biostudies-literature

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Effect of APOE ε4 allele on survival and fertility in an adverse environment.

van Exel Eric E Koopman Jacob J E JJE Bodegom David van DV Meij Johannes J JJ Knijff Peter de P Ziem Juventus B JB Finch Caleb E CE Westendorp Rudi G J RGJ

PloS one 20170706 7

<h4>Background</h4>The apolipoprotein-ε4 allele (APOE-ε4) is strongly associated with detrimental outcomes in affluent populations including atherosclerotic disease, Alzheimer's disease, and reduced lifespan. Despite these detrimental outcomes, population frequencies of APOE-ε4 are high. We hypothesize that the high frequency of APOE-ε4 was maintained because of beneficial effects during evolution when infectious pathogens were more prevalent and a major cause of mortality. We examined a rural G ...[more]

PMID: 28683096

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Project description:Background: Cholinergic deficiency has been suggested to associate with the abnormal accumulation of Aβ and tau for patients with Alzheimer's disease (AD). However, no studies have investigated the effect of APOE-ε4 and group differences in modulating the cholinergic basal forebrain–amygdala network for subjects with different levels of cognitive impairment. We evaluated the effect of APOE-ε4 on the cholinergic structural association and the neurocognitive performance for subjects with different levels of cognitive impairment. Methods: We used the structural brain magnetic resonance imaging scans from the Alzheimer's Disease Neuroimaging Initiative dataset. The study included cognitively normal (CN, n = 167) subjects and subjects with significant memory concern (SMC, n = 96), early mild cognitive impairment (EMCI, n = 146), late cognitive impairment (LMCI, n = 138), and AD (n = 121). Subjects were further categorized according to the APOE-ε4 allele carrier status. The main effects of APOE-ε4 and group difference on the brain volumetric measurements were assessed. Regression analyses were conducted to evaluate the associations among cholinergic structural changes, APOE-ε4 status, and cognitive performance. Results: We found that APOE-ε4 carriers in the disease group showed higher brain atrophy than non-carriers in the cholinergic pathway, while there is no difference between carriers and non-carriers in the CN group. APOE-ε4 allele carriers in the disease groups also exhibited a stronger cholinergic structural correlation than non-carriers did, while there is no difference between the carriers and non-carriers in the CN subjects. Disease subjects exhibited a stronger structural correlation in the cholinergic pathway than CN subjects did. Moreover, APOE-ε4 allele carriers in the disease group exhibited a stronger correlation between the volumetric changes and cognitive performance than non-carriers did, while there is no difference between carriers and non-carriers in CN subjects. Disease subjects exhibited a stronger correlation between the volumetric changes and cognitive performance than CN subjects did. Conclusion: Our results confirmed the effect of APOE-ε4 on and group differences in the associations with the cholinergic structural changes that may reflect impaired brain function underlying neurocognitive degeneration in AD.

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Effect of APOE ?4 allele on survival and fertility in an adverse environment.

Publications

Effect of APOE ε4 allele on survival and fertility in an adverse environment.

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