Genetic variation in apolipoprotein D affects the risk of Alzheimer disease in African-Americans.

Apolipoprotein D (APOD, gene; apoD, protein) is involved in neuroregenerative and neurodegenerative processes, and is upregulated in late-onset Alzheimer disease (AD) patients compared to nondemented controls. No genetic association studies have yet been carried out to investigate the role of APOD in AD. We have reported recently several sequence variants in the APOD gene, which are present exclusively among African blacks. In the present study we examined the role of four APOD genetic variants (Intron 1, codons 36, 108, 158) in modifying the risk of AD in 70 subjects with AD and 163 nondemented subjects from a population-based African-American cohort in Indianapolis. The Intron 1*2 allele was associated with an increased AD risk with an age, gender and APOE adjusted odds ratio (OR) of 2.29 (95% confidence interval [CI]: 1.19-4.43; P = 0.013), and this risk was confined to APOE*4 carriers (OR 3.12; 95% CI: 1.13-8.60; P = 0.028). The frequency of the codon 36/GT genotype was non-significantly higher in individuals with AD than nondemented subjects (4.3% vs. 1.2%) with an adjusted OR of 4.24 (95% CI: 0.66-27.14; P = 0.13). Our data suggest that the risk of AD among African-Americans may be modified by genetic variation in APOD. Larger population-based or case-control studies are needed to confirm the role of APOD genetic variation in AD.