Endophenotypes in normal brain morphology and Alzheimer's disease: a review.
Endophenotypes in normal brain morphology and Alzheimer's disease: a review.
复制标题
DOI：
10.1016/j.neuroscience.2009.04.006
复制
发表时间：
2009-11-24
期刊：
影响因子：
3.3
通讯作者：
Mayeux, R.
中科院分区：
文献类型：
--
作者：
Reitz, C.;Mayeux, R.
晚发性阿尔茨海默病是一种常见的老年复杂性疾病。虽然这些类型的疾病可能具有高度遗传性，但它们与单基因（孟德尔）疾病不同，因为它们的原因通常是多因素的，既有遗传因素，也有环境因素。与病因密切相关的遗传风险因素是淀粉样前体蛋白（APP）、早老素1（PSEN1）和早老素2（PSEN2）基因突变，这些基因在具有常染色体显性疾病遗传模式的多代大家族中发现，载脂蛋白E（APOE）ε4等位基因和分拣蛋白相关受体（SORL 1）基因。与迟发性阿尔茨海默病相关的环境因素包括抑郁症、各种血管危险因素、教育水平、头部创伤和雌激素替代疗法。这种复杂性可能有助于从进化的角度解释它们的高流行率，但病因的复杂性使识别疾病相关基因变得更加困难。“内表型”方法是一种测量表型变异的替代方法，可以帮助识别复杂遗传性状的易感基因。内表型在正常脑形态的遗传分析，特别是阿尔茨海默病的有用性将审查这些研究结果的疾病因果关系模型的影响。鉴于从基因型到终末期表型的途径充其量是迂回的，识别更接近遗传变异影响的内表型可能会加速将遗传变异与疾病联系起来的尝试。
Late-onset Alzheimer’s disease is a common complex disorder of old age. Though these types of disorders can be highly heritable, they differ from single-gene (Mendelian) diseases in that their causes are often multifactorial with both genetic and environmental components. Genetic risk factors that have been firmly implicated in the cause are mutations in the amyloid precursor protein (APP), presenilin 1 (PSEN1) and presenilin 2 (PSEN2) genes, which are found in large multi-generational families with an autosomal dominant pattern of disease inheritance, the apolipoprotein E (APOE)ε4 allele and the sortilin-related receptor (SORL1) gene. Environmental factors that have been associated with late-onset Alzheimer’s disease include depressive illness, various vascular risk factors, level of education, head trauma and estrogen replacement therapy. This complexity may help explain their high prevalence from an evolutionary perspective, but the etiologic complexity makes identification of disease-related genes much more difficult. The “endophenotype” approach is an alternative method for measuring phenotypic variation that may facilitate the identification of susceptibility genes for complexly inherited traits. The usefulness of endophenotypes in genetic analyses of normal brain morphology and, in particular for Alzheimer’s disease will be reviewed as will the implications of these findings for models of disease causation. Given that the pathways from genotypes to end-stage phenotypes are circuitous at best, identifying endophenotypes more proximal to the effects of genetic variation may expedite the attempts to link genetic variants to disorders.
登录
查看更多内容
影响因子：
30.8
作者：
Blacker, D;Wilcox, MA;Tanzi, RE
通讯作者：
Tanzi, RE
影响因子：
3.5
作者：
Blacker, D;Bertram, L;Tanzi, RE
通讯作者：
Tanzi, RE
影响因子：
10.4
作者：
Blangero, J;Williams, JT;Almasy, L
通讯作者：
Almasy, L
影响因子：
158.5
作者：
Bertram, L;Hiltunen, M;Tanzi, RE
通讯作者：
Tanzi, RE
影响因子：
9.9
作者：
Cosentino, S.;Scarmeas, N.;Stern, Y.
通讯作者：
Stern, Y.