Genetic variants ofABCA1 modify Alzheimer disease risk and quantitative traits related to ?-amyloid metabolism

Abstract
Linkage studies have provided evidence that one or more loci on chromosome 9q influence Alzheimer disease (AD). The gene encoding the ATP‐binding cassette A1 transporter (ABCA1) resides within proximity of previously identified linkage peaks and represents a plausible biological candidate for AD due to its central role in cellular lipid homeostasis. Several single nucleotide polymorphisms (SNPs) spanning ABCA1 have been genotyped and haplotype‐based association analyses performed in four independent case‐control samples, consisting of over 1,750 individuals from three European populations representing both early and late‐onset AD. Prominent effects were observed for a common (H2) and rarer haplotype (H5) that were enriched in AD cases across studied populations (odds ratio [OR] 1.59, 95% confidence interval [CI] 1.36–1.82; PABCA1 contribute to variable cerebrospinal fluid tau and beta amyloid (Aβ42) protein levels, and brain Aβ load. Results indicate that variants of ABCA1 may affect the risk of AD, providing further support for a genetic link between AD and cholesterol metabolism. Hum Mutat 23:358–367, 2004