Harvey R J, Rossor M N
Dementia Research Group, National Hospital for Neurology and Neurosurgery, London, England.
Alzheimer Dis Assoc Disord. 1995;9 Suppl 1:S7-13.
Alzheimer disease (AD) is a clinical and pathologic diagnosis and refers to the findings of neurofibrillary tangles and amyloid plaques in the brain of a patient with dementia. Clinically it is recognized that there are familial and sporadic forms, with further division into those with presenile and senile onset. Clinical, neuroimaging, neuropathological, and neurochemical studies have attempted to identify differences between cases with an earlier and later onset, but have not identified a categorical biologic difference between the two groups. Recent advances in the molecular genetics of familial Alzheimer disease (FAD) and the discovery of defined genetic abnormalities have provided a robust approach to distinguishing between early- and late-onset cases within the group of autosomal dominant FAD. The precise biologic classification made possible by molecular genetic analysis of FAD provides a benchmark against which phenotypic differences can be assessed. This article argues that future studies will be able to contrast early-onset familial versus late-onset familial disease, and early-onset familial versus early-onset sporadic disease. Previous reports of phenotypic differences within AD may have been the result of including FAD within early-onset groups, though this remains to be established.
阿尔茨海默病（AD）是一种临床和病理学诊断，指的是痴呆患者大脑中出现神经原纤维缠结和淀粉样斑块的情况。临床上公认存在家族性和散发性两种形式，还可进一步分为早发性和晚发性。临床、神经影像学、神经病理学和神经化学研究试图找出早发和晚发病例之间的差异，但尚未确定这两组之间存在明确的生物学差异。家族性阿尔茨海默病（FAD）分子遗传学的最新进展以及明确的基因异常的发现，为区分常染色体显性FAD组中的早发和晚发病例提供了有力方法。通过FAD分子遗传分析实现的精确生物学分类提供了一个基准，据此可以评估表型差异。本文认为，未来的研究将能够对比早发性家族性疾病与晚发性家族性疾病，以及早发性家族性疾病与早发性散发性疾病。之前关于AD内表型差异的报道可能是由于将FAD纳入早发组导致的，不过这一点仍有待确定。
