HLA-DR4 influences glial activity in Alzheimer's disease hippocampus.

The importance of inflammatory/immune mechanisms in Alzheimer's disease is supported by evidence that the human leukocyte antigen (HLA)-DR genotype influences risk of the disease, with a protective effect associated with the HLA-DR4 allele. We investigated the influence of the HLA-DR4 allele on glial activity, assessed by quantification of glial fibrillary acidic protein (GFAP), in hippocampal tissue from subjects with Alzheimer's disease. The mean GFAP level was significantly higher in Alzheimer's disease hippocampal specimens lacking the HLA-DR4 allele compared to specimens with similar neuropathological findings that were HLA-DR4 positive. Apolipoprotein E genotype had no influence on GFAP levels. These results indicate that HLA-DR4 may exert a protective influence on Alzheimer's disease via modulation of glial activity.