More than just risk for Alzheimer's disease: APOE ε4's impact on the aging brain

Justin M. Palmer; Matthew Huentelman; Lee Ryan

doi:10.1016/j.tins.2023.06.003

More than just risk for Alzheimer's disease: APOE ε4's impact on the aging brain

Justin M. Palmer, Matthew Huentelman, Lee Ryan

Research output: Contribution to journal › Review article › peer-review

6 Scopus citations

Abstract

The apolipoprotein ε4 (APOE ε4) allele is most commonly associated with increased risk for late-onset Alzheimer's disease (AD). However, recent longitudinal studies suggest that these risks are overestimated; most ε4 carriers will not develop dementia in their lifetime. In this article, we review new evidence regarding the impact of APOE ε4 on cognition among healthy older adults. We discuss emerging work from animal models suggesting that ε4 impacts brain structure and function in multiple ways that may lead to age-related cognitive impairment, independent from AD pathology. We discuss the importance of taking an individualized approach in future studies by incorporating biomarkers and neuroimaging methods that may better disentangle the phenotypic influences of APOE ε4 on the aging brain from prodromal AD pathology.

Original language	English (US)
Pages (from-to)	750-763
Number of pages	14
Journal	Trends in Neurosciences
Volume	46
Issue number	9
DOIs	https://doi.org/10.1016/j.tins.2023.06.003
State	Published - Sep 2023

Keywords

Alzheimer's risk
blood–brain barrier
cognitive aging
inflammation
neuronal dysfunction

ASJC Scopus subject areas

General Neuroscience

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10.1016/j.tins.2023.06.003

Cite this

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title = "More than just risk for Alzheimer's disease: APOE ε4's impact on the aging brain",

abstract = "The apolipoprotein ε4 (APOE ε4) allele is most commonly associated with increased risk for late-onset Alzheimer's disease (AD). However, recent longitudinal studies suggest that these risks are overestimated; most ε4 carriers will not develop dementia in their lifetime. In this article, we review new evidence regarding the impact of APOE ε4 on cognition among healthy older adults. We discuss emerging work from animal models suggesting that ε4 impacts brain structure and function in multiple ways that may lead to age-related cognitive impairment, independent from AD pathology. We discuss the importance of taking an individualized approach in future studies by incorporating biomarkers and neuroimaging methods that may better disentangle the phenotypic influences of APOE ε4 on the aging brain from prodromal AD pathology.",

keywords = "Alzheimer's risk, blood–brain barrier, cognitive aging, inflammation, neuronal dysfunction",

author = "Palmer, {Justin M.} and Matthew Huentelman and Lee Ryan",

note = "Publisher Copyright: {\textcopyright} 2023 Elsevier Ltd",

year = "2023",

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language = "English (US)",

volume = "46",

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T1 - More than just risk for Alzheimer's disease

T2 - APOE ε4's impact on the aging brain

AU - Palmer, Justin M.

AU - Huentelman, Matthew

AU - Ryan, Lee

PY - 2023/9

Y1 - 2023/9

N2 - The apolipoprotein ε4 (APOE ε4) allele is most commonly associated with increased risk for late-onset Alzheimer's disease (AD). However, recent longitudinal studies suggest that these risks are overestimated; most ε4 carriers will not develop dementia in their lifetime. In this article, we review new evidence regarding the impact of APOE ε4 on cognition among healthy older adults. We discuss emerging work from animal models suggesting that ε4 impacts brain structure and function in multiple ways that may lead to age-related cognitive impairment, independent from AD pathology. We discuss the importance of taking an individualized approach in future studies by incorporating biomarkers and neuroimaging methods that may better disentangle the phenotypic influences of APOE ε4 on the aging brain from prodromal AD pathology.

AB - The apolipoprotein ε4 (APOE ε4) allele is most commonly associated with increased risk for late-onset Alzheimer's disease (AD). However, recent longitudinal studies suggest that these risks are overestimated; most ε4 carriers will not develop dementia in their lifetime. In this article, we review new evidence regarding the impact of APOE ε4 on cognition among healthy older adults. We discuss emerging work from animal models suggesting that ε4 impacts brain structure and function in multiple ways that may lead to age-related cognitive impairment, independent from AD pathology. We discuss the importance of taking an individualized approach in future studies by incorporating biomarkers and neuroimaging methods that may better disentangle the phenotypic influences of APOE ε4 on the aging brain from prodromal AD pathology.

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KW - blood–brain barrier

KW - cognitive aging

KW - inflammation

KW - neuronal dysfunction

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DO - 10.1016/j.tins.2023.06.003

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More than just risk for Alzheimer's disease: APOE ε4's impact on the aging brain

Abstract

Keywords

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