The subunits of alpha2-macroglobulin receptor/low density lipoprotein receptor-related protein, native and transformed alpha2-macroglobulin and interleukin 6 in Alzheimer's disease.

To explore the role of alpha2-macroglobulin receptor/low density lipoprotein receptor-related protein (alpha2M-R/LRP) and its ligands in the pathogenesis of Alzheimer's disease (AD), antibodies were raised against its alpha- and beta-subunits and their expression pattern in the CNS in AD and control cases was correlated with that of native and transformed alpha2-macroglobulin (alpha2M) and interleukin 6 (IL-6). The transmembranous beta-subunit of alpha2M-R/LRP and transformed alpha2M were found in plaque cores in AD. Extramembranous alpha-subunit and native alpha2M immunoreactivities were localized in activated plaque-associated astrocytes and extracellularly in plaques. IL-6 immunostaining was associated with neurofibrillary changes, and was also found extracellularly in the center of plaques and in microglial cells. Our finding that plaque cores contain a second transmembranous protein fragment, the beta-subunit of alpha2 M-R/LRP, suggests ongoing membrane-protein degradation. By altering clearance and scavenger-like functions, fragmentation and breakdown of alpha2M-R/LRP may have an important role in extracellular amyloid deposition and the formation of neurofibrillary tangles in AD.