DOES EARLY-ONSET ALZHEIMER-DISEASE CONSTITUTE A DISTINCT SUBTYPE - THE CONTRIBUTION OF MOLECULAR-GENETICS

Alzheimer disease (AD) is a clinical and pathologic diagnosis and refe rs to the findings of neurofibrillary tangles and amyloid plaques in t he brain of a patient with dementia. Clinically it is recognized that there are familial and sporadic forms, with further division into thos e with presenile and senile onset. Clinical, neuroimaging, neuropathol ogical, and neurochemical studies have attempted to identify differenc es between cases with an earlier and later onset, but have not identif ied a categorical biologic difference between the two groups. Recent a dvances in the molecular genetics of familial Alzheimer disease (FAD) and the discovery of defined genetic abnormalities have provided a rob ust approach to distinguishing between early- and late-onset cases wit hin the group of autosomal dominant FAD. The precise biologic classifi cation made possible by molecular genetic analysis of FAD provides a b enchmark against which phenotypic differences can be assessed. This ar ticle 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 di fferences within AD may have been the result of including FAD within e arly-onset groups, though this remains to be established.