McGill Centre for Studies in Aging, McGill University Department of Neurology, Canada.
Can J Neurol Sci. 2012 Jul;39(4):436-45. doi: 10.1017/s0317167100013949.
Early-onset familial Alzheimer's disease (EOFAD) is a condition characterized by early onset dementia (age at onset < 65 years) and a positive family history for dementia. To date, 230 mutations in presenilin (PS1, PS2) and amyloid precursor protein (APP) genes have been identified in EOFAD. The mutations within these three genes (PS1/PS2/APP) affect a common pathogenic pathway in APP synthesis and proteolysis, which lead to excessive production of amyloid β. Compared with sporadic Alzheimer's disease (AD), EOFAD has some distinctive features including early age at onset, positive familial history, a variety of non-cognitive neurological symptoms and signs, and a more aggressive course. There is marked phenotypic heterogeneity among different mutations of EOFAD. Studies in presymptomatic mutation carriers reveal biomarkers abnormalities. EOFAD diagnosis is based on clinical and family history, neurological symptoms and examination, biomarker features, as well as genotyping in some cases. New therapeutic agents targeting amyloid formation may benefit EOFAD individuals.
早发性家族性阿尔茨海默病（EOFAD）的特征是早发性痴呆（发病年龄<65 岁）和痴呆阳性家族史。迄今为止，EOFAD 中已鉴定出早老素（PS1、PS2）和淀粉样前体蛋白（APP）基因中的 230 种突变。这三个基因（PS1/PS2/APP）中的突变影响 APP 合成和蛋白水解的共同致病途径，导致淀粉样β过度产生。与散发性阿尔茨海默病（AD）相比，EOFAD 具有一些独特的特征，包括发病年龄早、家族史阳性、多种非认知性神经症状和体征以及更具侵袭性的病程。EOFAD 的不同突变具有明显的表型异质性。对无症状突变携带者的研究揭示了生物标志物异常。EOFAD 的诊断基于临床和家族史、神经症状和检查、生物标志物特征以及在某些情况下的基因分型。针对淀粉样形成的新型治疗药物可能对 EOFAD 个体有益。
