Impact of APOE, Klotho, and sex on cognitive decline with aging

被引：1

作者：

Shibata, Kengo ^{[1
]}

Chen, Cheng ^{[2
,3
]}

Tai, Xin You ^{[1
,3
]}

Manohar, Sanjay G. ^{[1
,2
,3
]}

Husain, Masud ^{[1
,2
,3
]}

机构：

[1] Univ Oxford, Nuffield Dept Clin Neurosci, Oxford OX3 9DU, England

[2] Univ Oxford, Dept Expt Psychol, Oxford OX2 6GG, England

[3] Oxford Univ Hosp Trust, John Radcliffe Hosp, Div Clin Neurol, Oxford OX3 9DU, England

来源：

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA | 2025年 / 122卷 / 06期

关键词：

aging; antagonistic pleiotropy; apolipoprotein epsilon (apoe); cognition; klotho; APOLIPOPROTEIN-E GENOTYPE; LONGEVITY GENE KLOTHO; ALZHEIMER-DISEASE; CEREBROSPINAL-FLUID; HIPPOCAMPAL VOLUME; FUNCTIONAL VARIANT; MEMORY DECLINE; BRAIN ATROPHY; ALPHA-KLOTHO; EPSILON-4;

D O I：

10.1073/pnas.241604212

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

The effects of apolipoprotein E (APOE) and Klotho genes, both implicated in aging, on human cognition as a function of sex and age are yet to be definitively established. Here, we showed in the largest cohort studied to date (N = 320,861) that APOE homozygous epsilon 4 carriers had a greater decline in cognition with aging compared to epsilon 3 carriers (epsilon 3/epsilon 4 and epsilon 3/epsilon 3) as well as smaller hippocampi and amygdala (N = 29,510). Critically, sex and age differentially affected the decline in cognition. Younger (40 to 50 y) female homozygous epsilon 4 carriers showed a cognitive advantage over female epsilon 3 carriers, but this advantage was not present in males. By contrast, Klotho- VS heterozygosity did not affect cognition or brain volume, regardless of APOE genotype, sex, or age. These cognitive trajectories with aging demonstrate clear sex- dependent antagonistic pleiotropy effects of APOE epsilon 4, but no effects of Klotho genotype on cognition and brain volume.

引用

页数：11

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