阿尔茨海默病遗传风险谱。

IF 3 3区 医学 Q2 CLINICAL NEUROLOGY
Neurology-Genetics Pub Date : 2025-01-29 eCollection Date: 2025-02-01 DOI:10.1212/NXG.0000000000200224
Nicholas Karagas, Jessica E Young, Elizabeth E Blue, Suman Jayadev
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引用次数: 0

摘要

阿尔茨海默病(AD)是美国最常见的痴呆综合征,目前通过在临床认知障碍设置中存在淀粉样蛋白-β和tau蛋白生物标志物来确定。这些简单的诊断参数掩盖了阿尔茨海默病潜在风险和表现的遗传结构的巨大复杂性。在这篇综述中,我们提供了一个重点概述了阿尔茨海默病遗传学的现状。我们讨论了家族性常染色体显性基因的发现,与阿尔茨海默病相关的候选基因的鉴定,以及与一般人群相比具有更高患阿尔茨海默病风险的遗传变异。我们特别讨论了APOE ε4等位基因导致AD风险的重要特征。除了风险之外,我们还描述了该领域如何在理解可能预防AD的遗传因素方面取得进展。本文还讨论了多年来从AD全基因组关联研究中收集到的信息的生物学意义和实际局限性。读者将有一个最新的理解,我们在哪里,我们的努力,以了解遗传复杂性的层次在AD。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
The Spectrum of Genetic Risk in Alzheimer Disease.

Alzheimer disease (AD), the most common dementing syndrome in the United States, is currently established by the presence of amyloid-β and tau protein biomarkers in the setting of clinical cognitive impairment. These straightforward diagnostic parameters belie an immense complexity of genetic architecture underlying risk and presentation in AD. In this review, we provide a focused overview of the current state of AD genetics. We discuss the discovery of familial autosomal dominant genes, the identification of candidate genes associated with AD, and genetic variants conferring higher risk of developing AD compared with the general population. In particular, we discuss important features of AD risk due to the APOE ε4 allele. In addition to risk, we describe how the field has made headway understanding genetic factors that may protect from AD. The biological implications and practical limitations of information gleaned from genome-wide association studies in AD over the years are also discussed. The readers will have an up-to-date understanding of where we are in our efforts to understand the layers of genetic complexity in AD.

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来源期刊
Neurology-Genetics
Neurology-Genetics Medicine-Neurology (clinical)
CiteScore
6.30
自引率
3.20%
发文量
107
审稿时长
15 weeks
期刊介绍: Neurology: Genetics is an online open access journal publishing peer-reviewed reports in the field of neurogenetics. Original articles in all areas of neurogenetics will be published including rare and common genetic variation, genotype-phenotype correlations, outlier phenotypes as a result of mutations in known disease-genes, and genetic variations with a putative link to diseases. This will include studies reporting on genetic disease risk and pharmacogenomics. In addition, Neurology: Genetics will publish results of gene-based clinical trials (viral, ASO, etc.). Genetically engineered model systems are not a primary focus of Neurology: Genetics, but studies using model systems for treatment trials are welcome, including well-powered studies reporting negative results.
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