Absence of A673T variant in APP gene indicates an alternative protective mechanism contributing to longevity in Chinese individuals

Abstract

A673T, a rare variant in the amyloid-β precursor protein gene, shows a protective potential against Alzheimer's disease (AD) and age-related cognitive decline in an Icelandic population. Although A673T was observed independently in a Finnish population, this variant was absent in 8721 Asian subjects. The conflicting observations suggest that the contribution of A673T may be confined to Europeans and Americans rather than Asians. Nevertheless, A673T confers a protective function against AD and thus may be observed only in longevity subjects; thus it is not surprising to see its absence when the general populations or the patient cohorts were considered. To test whether the A673T contributes to the Chinese population, 1237 healthy longevity subjects (mean age 96.9 years) and 1404 matched younger controls (mean age 44.2 years) were genotyped for the variant. Our study failed to observe this variant in either the longevity subjects or the controls. Given the previous observation from Asians, our results suggest that the A673T variant is not involved in longevity in Chinese individuals; some other protective mechanisms may contribute to a lower incidence of AD in Chinese nonagenerians and centenarians.