Haass C
Department of Molecular Biology, University of Heidelberg, Mannheim, Germany.
Curr Opin Neurol. 1996 Aug;9(4):254-9.
Alzheimer's disease is a neurodegenerative disorder characterized by the massive and invariant accumulation of amyloid plaques in the brains of affected patients. In many cases Alzheimer's disease occurs in the absence of a prior history of the disease in other family members and is designated as sporadic, whereas in approximately 10% of patients, dominantly transmitted mutations within one of three genes are found. A few mutations have been identified within the gene encoding the beta-amyloid precursor protein; however, these mutations account for only about 1-3% of cases with familial Alzheimer's disease. In the majority of autosomal dominant cases (40-50%), mutations have been found in a gene localized to chromosome 14. The responsible gene, now called presenilin-1, has recently been identified and shown to encode a putative seven transmembrane domain protein. Surprisingly, a second highly homologous gene (named presenilin-2) was cloned shortly thereafter. It is localized on human chromosome 1 and is also involved in a small number of cases with familial Alzheimer's disease. Early data suggest that mutations found within the two genes cause early onset Alzheimer's disease by influencing the proteolytic processing of amyloid beta-peptide in a pathological manner.
阿尔茨海默病是一种神经退行性疾病，其特征是在受影响患者的大脑中大量且持续地积累淀粉样斑块。在许多情况下，阿尔茨海默病发生时，其他家庭成员没有该疾病的既往病史，被称为散发性病例；而在大约10%的患者中，发现三个基因之一存在显性遗传突变。在编码β-淀粉样前体蛋白的基因中已鉴定出一些突变；然而，这些突变仅占家族性阿尔茨海默病病例的约1 - 3%。在大多数常染色体显性病例（40 - 50%）中，已在定位于14号染色体的一个基因中发现突变。现在称为早老素-1的致病基因最近已被鉴定出来，并显示编码一种假定的七跨膜结构域蛋白。令人惊讶的是，此后不久克隆出了第二个高度同源的基因（名为早老素-2）。它定位于人类1号染色体，也与少数家族性阿尔茨海默病病例有关。早期数据表明，在这两个基因中发现的突变通过以病理方式影响淀粉样β肽的蛋白水解加工，导致早发性阿尔茨海默病。
