Expression of the small heat-shock protein alphaB-crystallin in tauopathies with glial pathology.
Intracellular accumulations of filamentous material composed of tau proteins are defining features of sporadic and familial neurodegenerative disorders termed "tauopathies." In Alzheimer's disease, the most common tauopathy, tau pathology is predominantly localized within neurons; however, robust glial pathology occurs in other tauopathies. Although the pathogenesis of tauopathies remains primarily unknown, molecular chaperones such as heat-shock proteins (HSPs) are implicated in these tau disorders as well as other neurodegenerative diseases characterized by the accumulation of insoluble protein aggregates such as alpha-synuclein in Parkinson's disease and polyglutamine in Huntington's disease. We analyzed a variety of tauopathies with antibodies to a panel of HSPs to determine their role in the pathogenesis of these disorders. Although HSPs are not found in neuronal tau inclusions, we demonstrate increased expression of the small HSP alphaB-crystallin in glial inclusions of both sporadic and familial tauopathies. alphaB-crystallin was observed in a subset of astrocytic and oligodendrocytic tau inclusions as well as the neuropil thread pathology in cellular processes, but the co-expression of alphaB-crystallin with tau inclusions was relatively specific to tauopathies with extensive glial pathology. Thus, increased alphaB-crystallin expression in glial tau inclusions may represent a response by glia to the accumulation of misfolded or aggregated tau protein that is linked to the pathogenesis of the glial pathology and distinct from mechanisms underlying neuronal tau pathology in neurodegenerative disease.
Dabir
Deepa V
DV
Department of Pathology and Laboratory Medicine, Center for Neurodegenerative Disease Research, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104-4283, USA.
Trojanowski
John Q
JQ
Richter-Landsberg
Christiane
C
Lee
Virginia M-Y
VM
Forman
Mark S
MS
D001253:Astrocytes / Q000378:metabolism / Q000473:pathology; D015153:Blotting, Western; D001921:Brain / Q000378:metabolism / Q000473:pathology*; D006801:Humans; D007150:Immunohistochemistry; D002479:Inclusion Bodies / Q000378:metabolism* / Q000473:pathology; D009457:Neuroglia / Q000473:pathology*; D009474:Neurons / Q000378:metabolism / Q000473:pathology; D009836:Oligodendroglia / Q000378:metabolism / Q000473:pathology; D024801:Tauopathies / Q000378:metabolism* / Q000473:pathology; D038203:alpha-Crystallin B Chain / Q000096:biosynthesis*; D016875:tau Proteins / Q000378:metabolism
D038203:alpha-Crystallin B Chain; D016875:tau Proteins