<i>APOE −491 promoter polymorphism is a risk factor for late-onset Alzheimer’s disease</i>

Abstract

The APOE e4 allele influences the occurrence of AD by lowering the age at disease onset.1 A case–control study of two (Spanish and North American) populations suggested an e4-independent association between an A/T polymorphism in the APOE regulatory region ( APOE −491) and sporadic AD,2 stronger in Spanish than in North American patients, thus suggesting genetic heterogeneity. Subsequent observations in different populations have been conflicting,3-6 ranging from a much weaker e4-independent association of APOE −491 and AD (alone3 or in association with other APOE polymorphisms4) to no5 or even a protective effect6 on the development of AD. So far, no association has been reported between this polymorphism and the age at AD onset. To explore this issue, we examined APOE −491 and e polymorphisms in Italian patients with AD and control subjects. A total of 358 white patients (age at disease onset 67.3 ± 9.3 [mean ± SD] years) affected by clinically probable AD according to the National Institute of Neurological and Communicative Disorders and Stroke/Alzheimer’s Disease and Related Disorders Association (NINCDS/ADRDA) criteria7 were enrolled. Patients were divided into those with an early onset (EO …