阿尔茨海默病的遗传学。
The genetics of Alzheimer disease.
机构信息
Genetics and Aging Research Unit, Department of Neurology, MassGeneral Institute for Neurodegenerative Disease, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts 02129, USA.
出版信息
Cold Spring Harb Perspect Med. 2012 Oct 1;2(10):a006296. doi: 10.1101/cshperspect.a006296.
Abstract
Family history is the second strongest risk factor for Alzheimer disease (AD) following advanced age. Twin and family studies indicate that genetic factors are estimated to play a role in at least 80% of AD cases. The inheritance of AD exhibits a dichotomous pattern. On one hand, rare mutations in APP, PSEN1, and PSEN2 virtually guarantee early-onset (<60 years) familial AD, which represents ∼5% of AD. On the other hand, common gene polymorphisms, such as the ε4 and ε2 variants of the APOE gene, can influence susceptibility for ∼50% of the common late-onset AD. These four genes account for 30%-50% of the inheritability of AD. Genome-wide association studies have recently led to the identification of 11 additional AD candidate genes. This paper reviews the past, present, and future attempts to elucidate the complex and heterogeneous genetic underpinnings of AD.
摘要
家族史是继年龄增长之后导致阿尔茨海默病（AD）的第二大最强风险因素。双胞胎和家族研究表明，遗传因素估计至少在 80%的 AD 病例中发挥作用。AD 的遗传呈现出二分模式。一方面，APP、PSEN1 和 PSEN2 中的罕见突变几乎可以保证早发性（<60 岁）家族性 AD，这占 AD 的约 5%。另一方面，常见的基因多态性，如 APOE 基因的 ε4 和 ε2 变体，可以影响约 50%的常见晚发性 AD 的易感性。这四个基因占 AD 可遗传性的 30%-50%。全基因组关联研究最近导致了另外 11 个 AD 候选基因的鉴定。本文综述了过去、现在和未来阐明 AD 复杂和异质性遗传基础的尝试。
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