THE SUBUNITS OF ALPHA(2)-MACROGLOBULIN RECEPTOR LOW-DENSITY-LIPOPROTEIN RECEPTOR-RELATED PROTEIN, NATIVE AND TRANSFORMED ALPHA(2)-MACROGLOBULIN AND INTERLEUKIN-6 IN ALZHEIMERS-DISEASE

To explore the role of alpha(2)-macroglobulin receptor/low density lip oprotein receptor-related protein (alpha(2)M-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 t he CNS in AD and control cases was correlated with that of native and transformed alpha(2)-macroglobulin (alpha(2)M) and interleukin 6 (IL-6 ). The transmembranous beta-subunit of alpha(2)M-R/LRP and transformed alpha(2)M were found in plaque cores in AD. Extramembranous alpha-sub unit and native alpha(2)M immunoreactivities were localized in activat ed plaque-associated astrocytes and extracellulary in plaques. IL-6 im munostaining was associated with neurofibrillary changes, and was also found extracellularly in the center of plaques and in microglial cell s. Our finding that plaque cores contain a second transmembranous prot ein fragment, the beta-subunit of alpha(2)M-R/LRP, suggests ongoing me mbrane-protein degradation. By altering clearance and scavenger-like f unctions, fragmentation and breakdown of alpha(2)M-R/LRP may have an i mportant role in extracellular amyloid deposition and the formation of neurofibrillary tangles in AD. (C) 1997 Elsevier Science B.V.