Levy-Lahad E, Tsuang D, Bird T D
Department of Medicine, Shaare Zedek Medical Center, Jerusalem, Israel.
J Geriatr Psychiatry Neurol. 1998 Summer;11(2):42-54. doi: 10.1177/089198879801100202.
Alzheimer's disease (AD) is a neurodegenerative disorder that is the most common cause of dementia in the elderly. It is a clinical-pathologic entity characterized by progressive dementia associated with the neuropathologic hallmarks of Abeta amyloid plaques, neurofibrillary tangles (NFTs), neuronal loss, and amyloid angiopathy. Three "causative" AD genes (i.e., genes in which a mutation is sufficient to result in clinical AD) for early-onset familial Alzheimer's disease (FAD) and one "susceptibility" gene that affects risk and age of onset of AD in familial and sporadic late-onset AD have been identified. The three causative genes are the amyloid precursor protein (APP gene) on chromosome 21, the presenilin-1 gene on chromosome 14, and the presenilin-2 gene on chromosome 1. The susceptibility gene is the apolipoprotein E (APOE) gene on chromosome 19. Investigations of the normal and aberrant function of these genes will provide insights into the mechanisms underlying AD and will suggest new strategies for therapeutic intervention.
阿尔茨海默病（AD）是一种神经退行性疾病，是老年人痴呆最常见的病因。它是一种临床病理实体，其特征为进行性痴呆，并伴有β淀粉样蛋白斑块、神经原纤维缠结（NFTs）、神经元丢失和淀粉样血管病等神经病理学特征。已确定了三个早发性家族性阿尔茨海默病（FAD）的“致病”AD基因（即突变足以导致临床AD的基因），以及一个影响家族性和散发性晚发性AD发病风险和发病年龄的“易感”基因。这三个致病基因分别是21号染色体上的淀粉样前体蛋白（APP基因）、14号染色体上的早老素-1基因和1号染色体上的早老素-2基因。易感基因是19号染色体上的载脂蛋白E（APOE）基因。对这些基因正常和异常功能的研究将有助于深入了解AD的发病机制，并为治疗干预提供新策略。
