ABCA7 risk genotype diminishes the neuroprotective value of aerobic fitness in healthy older African Americans

Chelsie N. Berg, Neha Sinha, Mark Gluck

Research output: Contribution to journalArticle

Abstract

Although the association of ABCA7 risk variants with Alzheimer's disease (AD) has been established worldwide, its effect size on the relative odds of being diagnosed with AD is significantly higher in African Americans. Across ethnicities, two common ABCA7 loci (rs115550680 and rs3764650) have been confirmed to increase the risk of AD. While ABCA7 rs115550680 has been linked to the development of late-onset AD in African Americans, no association between ABCA7 variant rs3764650 and AD has been found in this population. In order to elucidate the influence of ABCA7 rs3764650 on AD risk in African Americans, we sought to investigate the relationship between this variant, aerobic fitness, and cognition. The present study tested the hypothesis that in African Americans, ABCA7 rs3764650 confers an indirect risk for AD via its interaction with aerobic fitness, a modifiable lifestyle factor known to attenuate AD-related neuropathology. In a case-control sample of 100 healthy African Americans, we observed that ABCA7 rs3764650 genotype modulates the association between aerobic fitness and a cognitive assessment of generalization following rule learning. For carriers of the non-risk genotype, higher levels of aerobic fitness were significantly associated with fewer generalization errors, while carriers of the risk genotype did not show any relationship between aerobic fitness and generalization. Our findings imply that ABCA7 rs3764650 risk genotype may diminish the neuroprotective effects of aerobic fitness, and, they suggest differing risk patterns between cognitive decline and fitness by ABCA7 genotype. Thus, in African Americans the interactive effects of ABCA7 rs3764650 and aerobic fitness likely compound overall ABCA7-related AD risk, and may contribute to health disparities whereby African Americans are at a higher risk for dementia, with double the prevalence of AD.

Original languageEnglish (US)
Article number73
JournalFrontiers in Aging Neuroscience
Volume11
Issue numberAPR
DOIs
StatePublished - Jan 1 2019

Fingerprint

African Americans
Alzheimer Disease
Genotype
Neuroprotective Agents
Cognition
Dementia
Life Style
Odds Ratio
Learning
Health

All Science Journal Classification (ASJC) codes

  • Aging
  • Cognitive Neuroscience

Keywords

  • ABCA7
  • Aerobic fitness (VO2 max)
  • African American
  • Alzheimer's disease
  • Cognitive decline

Cite this

@article{82546f6731c94de593524046c4403741,
title = "ABCA7 risk genotype diminishes the neuroprotective value of aerobic fitness in healthy older African Americans",
abstract = "Although the association of ABCA7 risk variants with Alzheimer's disease (AD) has been established worldwide, its effect size on the relative odds of being diagnosed with AD is significantly higher in African Americans. Across ethnicities, two common ABCA7 loci (rs115550680 and rs3764650) have been confirmed to increase the risk of AD. While ABCA7 rs115550680 has been linked to the development of late-onset AD in African Americans, no association between ABCA7 variant rs3764650 and AD has been found in this population. In order to elucidate the influence of ABCA7 rs3764650 on AD risk in African Americans, we sought to investigate the relationship between this variant, aerobic fitness, and cognition. The present study tested the hypothesis that in African Americans, ABCA7 rs3764650 confers an indirect risk for AD via its interaction with aerobic fitness, a modifiable lifestyle factor known to attenuate AD-related neuropathology. In a case-control sample of 100 healthy African Americans, we observed that ABCA7 rs3764650 genotype modulates the association between aerobic fitness and a cognitive assessment of generalization following rule learning. For carriers of the non-risk genotype, higher levels of aerobic fitness were significantly associated with fewer generalization errors, while carriers of the risk genotype did not show any relationship between aerobic fitness and generalization. Our findings imply that ABCA7 rs3764650 risk genotype may diminish the neuroprotective effects of aerobic fitness, and, they suggest differing risk patterns between cognitive decline and fitness by ABCA7 genotype. Thus, in African Americans the interactive effects of ABCA7 rs3764650 and aerobic fitness likely compound overall ABCA7-related AD risk, and may contribute to health disparities whereby African Americans are at a higher risk for dementia, with double the prevalence of AD.",
keywords = "ABCA7, Aerobic fitness (VO2 max), African American, Alzheimer's disease, Cognitive decline",
author = "Berg, {Chelsie N.} and Neha Sinha and Mark Gluck",
year = "2019",
month = "1",
day = "1",
doi = "10.3389/fnagi.2019.00073",
language = "English (US)",
volume = "11",
journal = "Frontiers in Aging Neuroscience",
issn = "1663-4365",
publisher = "Frontiers Research Foundation",
number = "APR",

}

ABCA7 risk genotype diminishes the neuroprotective value of aerobic fitness in healthy older African Americans. / Berg, Chelsie N.; Sinha, Neha; Gluck, Mark.

In: Frontiers in Aging Neuroscience, Vol. 11, No. APR, 73, 01.01.2019.

Research output: Contribution to journalArticle

TY - JOUR

T1 - ABCA7 risk genotype diminishes the neuroprotective value of aerobic fitness in healthy older African Americans

AU - Berg, Chelsie N.

AU - Sinha, Neha

AU - Gluck, Mark

PY - 2019/1/1

Y1 - 2019/1/1

N2 - Although the association of ABCA7 risk variants with Alzheimer's disease (AD) has been established worldwide, its effect size on the relative odds of being diagnosed with AD is significantly higher in African Americans. Across ethnicities, two common ABCA7 loci (rs115550680 and rs3764650) have been confirmed to increase the risk of AD. While ABCA7 rs115550680 has been linked to the development of late-onset AD in African Americans, no association between ABCA7 variant rs3764650 and AD has been found in this population. In order to elucidate the influence of ABCA7 rs3764650 on AD risk in African Americans, we sought to investigate the relationship between this variant, aerobic fitness, and cognition. The present study tested the hypothesis that in African Americans, ABCA7 rs3764650 confers an indirect risk for AD via its interaction with aerobic fitness, a modifiable lifestyle factor known to attenuate AD-related neuropathology. In a case-control sample of 100 healthy African Americans, we observed that ABCA7 rs3764650 genotype modulates the association between aerobic fitness and a cognitive assessment of generalization following rule learning. For carriers of the non-risk genotype, higher levels of aerobic fitness were significantly associated with fewer generalization errors, while carriers of the risk genotype did not show any relationship between aerobic fitness and generalization. Our findings imply that ABCA7 rs3764650 risk genotype may diminish the neuroprotective effects of aerobic fitness, and, they suggest differing risk patterns between cognitive decline and fitness by ABCA7 genotype. Thus, in African Americans the interactive effects of ABCA7 rs3764650 and aerobic fitness likely compound overall ABCA7-related AD risk, and may contribute to health disparities whereby African Americans are at a higher risk for dementia, with double the prevalence of AD.

AB - Although the association of ABCA7 risk variants with Alzheimer's disease (AD) has been established worldwide, its effect size on the relative odds of being diagnosed with AD is significantly higher in African Americans. Across ethnicities, two common ABCA7 loci (rs115550680 and rs3764650) have been confirmed to increase the risk of AD. While ABCA7 rs115550680 has been linked to the development of late-onset AD in African Americans, no association between ABCA7 variant rs3764650 and AD has been found in this population. In order to elucidate the influence of ABCA7 rs3764650 on AD risk in African Americans, we sought to investigate the relationship between this variant, aerobic fitness, and cognition. The present study tested the hypothesis that in African Americans, ABCA7 rs3764650 confers an indirect risk for AD via its interaction with aerobic fitness, a modifiable lifestyle factor known to attenuate AD-related neuropathology. In a case-control sample of 100 healthy African Americans, we observed that ABCA7 rs3764650 genotype modulates the association between aerobic fitness and a cognitive assessment of generalization following rule learning. For carriers of the non-risk genotype, higher levels of aerobic fitness were significantly associated with fewer generalization errors, while carriers of the risk genotype did not show any relationship between aerobic fitness and generalization. Our findings imply that ABCA7 rs3764650 risk genotype may diminish the neuroprotective effects of aerobic fitness, and, they suggest differing risk patterns between cognitive decline and fitness by ABCA7 genotype. Thus, in African Americans the interactive effects of ABCA7 rs3764650 and aerobic fitness likely compound overall ABCA7-related AD risk, and may contribute to health disparities whereby African Americans are at a higher risk for dementia, with double the prevalence of AD.

KW - ABCA7

KW - Aerobic fitness (VO2 max)

KW - African American

KW - Alzheimer's disease

KW - Cognitive decline

UR - http://www.scopus.com/inward/record.url?scp=85068322362&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85068322362&partnerID=8YFLogxK

U2 - 10.3389/fnagi.2019.00073

DO - 10.3389/fnagi.2019.00073

M3 - Article

VL - 11

JO - Frontiers in Aging Neuroscience

JF - Frontiers in Aging Neuroscience

SN - 1663-4365

IS - APR

M1 - 73

ER -