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

Brain Research
D R ThalG Birkenmeier

Abstract

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.

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Citations

Jul 16, 2002·Brain Research. Molecular Brain Research·Katrin ArélinBradley T Hyman
Oct 16, 2009·Nature·Richard J PerrinDavid M Holtzman
May 7, 2014·Proceedings of the National Academy of Sciences of the United States of America·Amy R WyattChristopher M Dobson
Jan 7, 2011·Journal of Neural Transmission·Harshvardhan RolyanDietmar Rudolf Thal
Nov 26, 2003·Experimental Neurology·G BirkenmeierA Reichenbach
Apr 21, 2009·Journal of Cellular and Molecular Medicine·Prashant R BharadwajIan G Macreadie
Feb 26, 1999·Journal of Neurochemistry·S MentzE A Komives
Mar 10, 2019·Proceedings of the National Academy of Sciences of the United States of America·Jordan H CaterAmy R Wyatt
Aug 21, 2019·Oxidative Medicine and Cellular Longevity·Jordan H CaterAmy R Wyatt

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