A high incidence of apolipoprotein E epsilon 4 allele in middle-aged non-demented subjects with cerebral amyloid beta protein deposits

We examined the apolipoprotein E (ApoE) genotypes of 19 middle-aged non-dem ented subjects with cerebral amyloid beta protein (A beta) deposits, and co mpared the results with those of 16 patients with sporadic Alzheimer's dise ase (AD) and those of 34 age-matched controls. The frequency of the ApoE ep silon 4 allele was higher (P = 0.0256) in these 19 subjects (0.211) than in controls (0.059), and was close to that in AD patients (0.281). This resul t suggests that middle-aged non-demented subjects with cerebral A beta depo sits are at high risk of developing AD, and that the diffuse A beta deposit s in these cases represent an early stage of AD pathology. We speculate tha t in the majority of late-onset sporadic AD patients, cerebral A beta depos ition commences when these patients are in their forties or fifties, and th at the pathological process progresses gradually, taking 20 to 30 years for clinical manifestation of dementia.