The Causal Relationship between Genetically Predicted Biological Aging, Alzheimer’s Disease and Cognitive Function: A Mendelian Randomisation Study

Y. Hao, W. Tian, B. Xie, X. Fu, S. Wang, Yu Yang
{"title":"The Causal Relationship between Genetically Predicted Biological Aging, Alzheimer’s Disease and Cognitive Function: A Mendelian Randomisation Study","authors":"Y. Hao, W. Tian, B. Xie, X. Fu, S. Wang, Yu Yang","doi":"10.14283/jpad.2024.128","DOIUrl":null,"url":null,"abstract":"<p>Aging is one of the most important risk factors for Alzheimer’s disease (AD). Biological aging is a better indicator of the body’s functional state than age (chronological aging). Leukocyte telomere length (LTL) and epigenetic clocks constructed from DNA methylation patterns have emerged as reliable markers of biological aging. Recent studies have shown that it may be possible to slow down or even reverse biological aging, offering promising prospects for treating AD. Several observational studies have reported an association between biological aging, AD, and cognitive function, but the causality behind this association and the effects of different biological aging markers on AD risk and cognitive function remain unclear. Therefore, we explored the causal relationship between them by Mendelian randomization (MR) study. Inverse-variance weighted (IVW) method is the most dominant analytical method in MR studies, which is a weighted average of estimates from different genotype combinations, and this weighted average provides an overall estimate of the causal effect. The results of the IVW analyses showed that HannumAge acceleration and LTL shortening were able to increase the risk of late-onset AD (LOAD), but not early-onset AD (EOAD). Excellent prospective memory and fluid intelligence are potentially protective against GrimAge acceleration. GrimAge acceleration and HorvathAge acceleration increase the risk of LOAD through effects on LTL. Our findings provide important insights into the role of biological aging in the pathogenesis of AD, while also highlighting the interplay of different biological aging markers and their complexity in different AD subtypes.</p>","PeriodicalId":22711,"journal":{"name":"The Journal of Prevention of Alzheimer's Disease","volume":"24 2 1","pages":""},"PeriodicalIF":4.3000,"publicationDate":"2024-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"The Journal of Prevention of Alzheimer's Disease","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.14283/jpad.2024.128","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"BUSINESS","Score":null,"Total":0}
引用次数: 0

Abstract

Aging is one of the most important risk factors for Alzheimer’s disease (AD). Biological aging is a better indicator of the body’s functional state than age (chronological aging). Leukocyte telomere length (LTL) and epigenetic clocks constructed from DNA methylation patterns have emerged as reliable markers of biological aging. Recent studies have shown that it may be possible to slow down or even reverse biological aging, offering promising prospects for treating AD. Several observational studies have reported an association between biological aging, AD, and cognitive function, but the causality behind this association and the effects of different biological aging markers on AD risk and cognitive function remain unclear. Therefore, we explored the causal relationship between them by Mendelian randomization (MR) study. Inverse-variance weighted (IVW) method is the most dominant analytical method in MR studies, which is a weighted average of estimates from different genotype combinations, and this weighted average provides an overall estimate of the causal effect. The results of the IVW analyses showed that HannumAge acceleration and LTL shortening were able to increase the risk of late-onset AD (LOAD), but not early-onset AD (EOAD). Excellent prospective memory and fluid intelligence are potentially protective against GrimAge acceleration. GrimAge acceleration and HorvathAge acceleration increase the risk of LOAD through effects on LTL. Our findings provide important insights into the role of biological aging in the pathogenesis of AD, while also highlighting the interplay of different biological aging markers and their complexity in different AD subtypes.

Abstract Image

查看原文
分享 分享
微信好友 朋友圈 QQ好友 复制链接
本刊更多论文
基因预测的生物衰老、阿尔茨海默病和认知功能之间的因果关系:孟德尔随机研究
衰老是阿尔茨海默病(AD)最重要的风险因素之一。与年龄(计时衰老)相比,生物衰老是人体功能状态的更好指标。白细胞端粒长度(LTL)和根据 DNA 甲基化模式构建的表观遗传时钟已成为生物衰老的可靠标志。最近的研究表明,延缓甚至逆转生物衰老是可能的,这为治疗注意力缺失症提供了广阔的前景。一些观察性研究报告了生物衰老、AD 和认知功能之间的关联,但这种关联背后的因果关系以及不同生物衰老标志物对 AD 风险和认知功能的影响仍不清楚。因此,我们通过孟德尔随机化(MR)研究探讨了它们之间的因果关系。逆方差加权(IVW)法是MR研究中最主要的分析方法,它是对不同基因型组合的估计值进行加权平均,这种加权平均提供了对因果效应的总体估计。IVW分析结果显示,HannumAge加速和LTL缩短能够增加晚发AD(LOAD)的风险,但不会增加早发AD(EOAD)的风险。出色的前瞻性记忆和流体智力可能对格林年龄加速具有保护作用。GrimAge加速和HorvathAge加速通过对LTL的影响增加了LOAD的风险。我们的研究结果为了解生物衰老在AD发病机制中的作用提供了重要见解,同时也强调了不同生物衰老标志物的相互作用及其在不同AD亚型中的复杂性。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
求助全文
约1分钟内获得全文 去求助
来源期刊
The Journal of Prevention of Alzheimer's Disease
The Journal of Prevention of Alzheimer's Disease Medicine-Psychiatry and Mental Health
CiteScore
9.20
自引率
0.00%
发文量
0
期刊介绍: The JPAD Journal of Prevention of Alzheimer’Disease will publish reviews, original research articles and short reports to improve our knowledge in the field of Alzheimer prevention including: neurosciences, biomarkers, imaging, epidemiology, public health, physical cognitive exercise, nutrition, risk and protective factors, drug development, trials design, and heath economic outcomes.JPAD will publish also the meeting abstracts from Clinical Trial on Alzheimer Disease (CTAD) and will be distributed both in paper and online version worldwide.We hope that JPAD with your contribution will play a role in the development of Alzheimer prevention.
期刊最新文献
Association between Cognitive Reserve Indicator and Chronic Disease-Free Survival: A Large Community-Based Longitudinal Study Phase 1 Studies of the Anti-Tau Monoclonal Antibody JNJ-63733657 in Healthy Participants and Participants with Alzheimer’s Disease Roles of TREM2 in the Pathological Mechanism and the Therapeutic Strategies of Alzheimer’s Disease Development and Validation the Mobile Toolbox (MTB) Spelling Test Correlates of Subjective Cognitive Decline in Black American Men
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
现在去查看 取消
×
提示
确定
0
微信
客服QQ
Book学术公众号 扫码关注我们
反馈
×
意见反馈
请填写您的意见或建议
请填写您的手机或邮箱
已复制链接
已复制链接
快去分享给好友吧!
我知道了
×
扫码分享
扫码分享
Book学术官方微信
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术
文献互助 智能选刊 最新文献 互助须知 联系我们:info@booksci.cn
Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。
Copyright © 2023 Book学术 All rights reserved.
ghs 京公网安备 11010802042870号 京ICP备2023020795号-1