Roks Gerwin
Afdeling neurologie, Elisabeth ziekenhuis, postbus 90151, 5000 LC, Tilburg.
Tijdschr Gerontol Geriatr. 2003 Feb;34(1):13-20.
Research in the field of Alzheimer's disease has shown that genetic factors play an important role in the aetiology of the disease. Until now, four genes have been found to be implicated in Alzheimer's disease. Mutations in the amyloid precursor protein gene (APP) and the presenilin genes (PSEN1 en PSEN2) cause early onset Alzheimer's disease. These mutations segregate in an autosomal dominant pattern. The fourth gene involved in Alzheimer's disease is the apolipoprotein E gene (APOE). Carriers of the E4 variant of APOE have an increased risk of Alzheimer's disease. Being a carrier of this E4 variant increases the risk of both early- and late-onset Alzheimer's disease. Of the four Alzheimer-genes, APOE plays the most important role in the general population. Mutations in APP and the presenilin genes account for less than 1% of the prevalence of the disease in the general population compared to 10-17% for the APOE variation. Up till now the impact of genetics in daily clinical practice is very limited. However, genetics has caused major progress in molecular-biological knowledge, especially of the amyloid metabolism, creating optimism about novel biological markers and eventually therapeutic strategies. In Alzheimer's genetics break-throughs are to be expected using classical methods such as the candidate-gene or linkage approach. Novel strategies such as genetic research in isolated populations are promising.
阿尔茨海默病领域的研究表明，遗传因素在该疾病的病因学中起着重要作用。到目前为止，已发现有四个基因与阿尔茨海默病有关。淀粉样前体蛋白基因（APP）和早老素基因（PSEN1和PSEN2）的突变会导致早发性阿尔茨海默病。这些突变以常染色体显性模式遗传。与阿尔茨海默病相关的第四个基因是载脂蛋白E基因（APOE）。APOE的E4变体携带者患阿尔茨海默病的风险增加。携带这种E4变体既会增加早发性也会增加晚发性阿尔茨海默病的风险。在这四个与阿尔茨海默病相关的基因中，APOE在普通人群中起着最重要的作用。与APOE变异导致的疾病患病率为10 - 17%相比，APP和早老素基因的突变在普通人群中导致的疾病患病率不到1%。到目前为止，遗传学在日常临床实践中的影响非常有限。然而，遗传学在分子生物学知识方面取得了重大进展，尤其是在淀粉样蛋白代谢方面，这为新型生物标志物以及最终的治疗策略带来了希望。在阿尔茨海默病研究中，使用候选基因或连锁分析等经典方法有望取得突破。诸如对孤立人群进行基因研究等新策略很有前景。
