EXPRESSION OF DIFFERENTIAL IMMUNE FACTORS IN TEMPORAL CORTEX AND CEREBELLUM - THE ROLE OF ALPHA-1-ANTICHYMOTRYPSIN, APOLIPOPROTEIN-E, AND REACTIVE GLIA IN THE PROGRESSION OF ALZHEIMERS-DISEASE

A variety of factors and processes have been implicated in the develop ment and progression of the pathology of Alzheimer's Disease (AD), inc luding amyloid fragment deposition, reactive gliosis, alpha-1-antichym otrypsin (ACT), and apolipoprotein E (APOE). Carriers of the APOE 4 al lele have been shown to have an enhanced risk; of developing AD, and t he ACT signal peptide A/A genotype may modify the APOE epsilon 4 risk. The protein products of these genes have been shown to enhance conver sion of diffuse beta amyloid (A beta) fibrils, which are found in diff use plaques, to the fibrillar form found in neuritic plaques. In affec ted regions of AD brain, ACT and APOE colocalize with A beta deposits and reactive microglia and astrocytes. We examined the regional distri bution of ACT, APOE, and reactive glia in temporal cortex, where neuri tic plaques are abundant, and cerebellum (in areas where diffuse plaqu es but not neuritic plaques accumulate) to examine the relationship of these markers to the deposition of A beta. In temporal cortex, ACT an d APOE staining was localized to plaque-like profiles, reactive astroc ytes, and blood vessels; human leukocyte antigen-DR (HLA-DR) and glial fibrillary acidic protein (GFAP) staining revealed focal clusters of reactive microglia and astrocytes. In cerebellum, ACT and APOE immunor eactivity was never localized to plaque-like profiles but was weakly l ocalized to unreactive astrocytes; weak HLA-DR and GFAP immunoreactivi ty was present on quiescent microglia throughout the cerebellum. The l ack of fibrillar amyloid deposits in cerebellum, despite the presence of well-characterized markers thought to mediate the production of A b eta, suggests that this brain region may be lacking certain factors ne cessary for fibril formation or that the cerebellum responds different ly to stimuli that successfully mediate inflammation in affected corte x. (C) 1998 Wiley-Liss, Inc.