A Comprehensive Review of Genetic Risk Factors for Alzheimer's Disease Development.

IF 3.3 4区医学 Q2 GENETICS & HEREDITY

Current gene therapy Pub Date : 2025-09-19 DOI:10.2174/0115665232397101250916050247

Aniket Kakkar, Harpreet Singh, Amit Anand, Arun Kumar Mishra, Arvind Kumar, Hitesh Chopra

{"title":"A Comprehensive Review of Genetic Risk Factors for Alzheimer's Disease Development.","authors":"Aniket Kakkar, Harpreet Singh, Amit Anand, Arun Kumar Mishra, Arvind Kumar, Hitesh Chopra","doi":"10.2174/0115665232397101250916050247","DOIUrl":null,"url":null,"abstract":"<p><p>Alzheimer's Disease (AD) is a progressive neurodegenerative disorder with a complex genetic basis involving both rare mutations and common variants. This review provides a comprehensive synthesis of established and emerging genetic risk factors implicated in AD pathogenesis. Mendelian forms are strongly associated with mutations in APP, PSEN1, and PSEN2, whereas the APOE ε4 allele remains the most robust genetic risk factor for late-onset AD. Recent Genome- Wide Association Studies (GWAS) have uncovered additional susceptibility loci, including TREM2, CLU, ABCA7, and SORL1, which reflect diverse biological pathways such as amyloid metabolism, lipid regulation, and immune response. The review also highlights the roles of epigenetic mechanisms such as DNA methylation and histone modifications, as well as geneenvironment interactions in modulating disease risk and progression. Although substantial progress has been made in identifying genetic contributors, translating these findings into clinical applications remains challenging. This article underscores the need for integrative, multi-omic approaches and population-diverse studies to enhance risk prediction and enable personalized interventions for prevention and therapy in AD.</p>","PeriodicalId":10798,"journal":{"name":"Current gene therapy","volume":" ","pages":""},"PeriodicalIF":3.3000,"publicationDate":"2025-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Current gene therapy","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.2174/0115665232397101250916050247","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"GENETICS & HEREDITY","Score":null,"Total":0}

引用次数: 0

Abstract

Alzheimer's Disease (AD) is a progressive neurodegenerative disorder with a complex genetic basis involving both rare mutations and common variants. This review provides a comprehensive synthesis of established and emerging genetic risk factors implicated in AD pathogenesis. Mendelian forms are strongly associated with mutations in APP, PSEN1, and PSEN2, whereas the APOE ε4 allele remains the most robust genetic risk factor for late-onset AD. Recent Genome- Wide Association Studies (GWAS) have uncovered additional susceptibility loci, including TREM2, CLU, ABCA7, and SORL1, which reflect diverse biological pathways such as amyloid metabolism, lipid regulation, and immune response. The review also highlights the roles of epigenetic mechanisms such as DNA methylation and histone modifications, as well as geneenvironment interactions in modulating disease risk and progression. Although substantial progress has been made in identifying genetic contributors, translating these findings into clinical applications remains challenging. This article underscores the need for integrative, multi-omic approaches and population-diverse studies to enhance risk prediction and enable personalized interventions for prevention and therapy in AD.

查看原文本刊更多论文

阿尔茨海默病发展的遗传危险因素的综合综述。

阿尔茨海默病（AD）是一种进行性神经退行性疾病，具有复杂的遗传基础，包括罕见突变和常见变异。本文综述了与阿尔茨海默病发病机制相关的已建立的和新出现的遗传危险因素。孟德尔形式与APP、PSEN1和PSEN2突变密切相关，而APOE ε4等位基因仍然是迟发性AD最强大的遗传风险因素。最近的全基因组关联研究（GWAS）发现了其他易感位点，包括TREM2、CLU、ABCA7和SORL1，它们反映了淀粉样蛋白代谢、脂质调节和免疫反应等多种生物学途径。该综述还强调了表观遗传机制（如DNA甲基化和组蛋白修饰）以及基因环境相互作用在调节疾病风险和进展中的作用。尽管在确定遗传因素方面取得了实质性进展，但将这些发现转化为临床应用仍然具有挑战性。这篇文章强调了整合、多组学方法和人群多样化研究的必要性，以加强AD的风险预测和个性化干预预防和治疗。

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分钟内获得全文求助全文

来源期刊

Current gene therapy 医学-遗传学

CiteScore

6.70

自引率

2.80%

发文量

期刊介绍： Current Gene Therapy is a bi-monthly peer-reviewed journal aimed at academic and industrial scientists with an interest in major topics concerning basic research and clinical applications of gene and cell therapy of diseases. Cell therapy manuscripts can also include application in diseases when cells have been genetically modified. Current Gene Therapy publishes full-length/mini reviews and original research on the latest developments in gene transfer and gene expression analysis, vector development, cellular genetic engineering, animal models and human clinical applications of gene and cell therapy for the treatment of diseases. Current Gene Therapy publishes reviews and original research containing experimental data on gene and cell therapy. The journal also includes manuscripts on technological advances, ethical and regulatory considerations of gene and cell therapy. Reviews should provide the reader with a comprehensive assessment of any area of experimental biology applied to molecular medicine that is not only of significance within a particular field of gene therapy and cell therapy but also of interest to investigators in other fields. Authors are encouraged to provide their own assessment and vision for future advances. Reviews are also welcome on late breaking discoveries on which substantial literature has not yet been amassed. Such reviews provide a forum for sharply focused topics of recent experimental investigations in gene therapy primarily to make these results accessible to both clinical and basic researchers. Manuscripts containing experimental data should be original data, not previously published.