Tau protein in the glial cytoplasmic inclusions of multiple system atrophy can be distinguished from abnormal tau in Alzheimer's disease.
The glial cytoplasmic inclusion (GCI) is a histological hallmark for multiple system atrophy (MSA). These inclusions are in oligodendrocytes, contain microtubular structures of 20-30 nm diameter, and can be labelled immunohistochemically with antibodies to ubiquitin, alphaB-crystallin, alpha- and beta-tubulin, and the microtubule-associated protein tau. GCIs have been compared with neuronal inclusions in other neurodegenerative disorders including the neurofibrillary tangles (NFTs) found in Alzheimer's disease (AD), which also contain tau protein. In order to determine whether the tau protein of GCIs in MSA is similar to that observed in AD we used a panel of antibodies to phosphorylation-independent (SMI51, TP007, TP70), dephosphorylation-dependent (Tau.1), and phosphorylation-dependent antibodies to tau and neurofilaments (AT8, AT180, AT270, SMI31, SMI34, RT97, BF10, 8D8). Immunohistochemistry was performed on paraffin wax-embedded brain tissue of the cerebellum, brainstem, and frontal lobes (Brodmann areas 4/6) of ten clinically and neuropathologically well-characterised cases of MSA, two cases of AD, and two normal controls. The NFTs of the AD cases were labelled with all the phosphorylation-dependent and phosphorylation-independent antibodies and with Tau.1 only after treatment with alkaline phosphatase. In contrast, GCIs were immunolabelled by the phosphorylation-independent antibodies and Tau.1, but not by the phosphorylation-dependent antibodies. These data demonstrate that the tau in GCIs is different from the abnormally phosphorylated tau found in AD and is similar to normal adult tau. The mechanism causing the abnormal accumulation of tau in GCIs remains to be elucidated.
Cairns
N J
NJ
Department of Neuropathology, Institute of Psychiatry, De Crespigny Park, London, UK. n.cairns@iop.bpmf.ac.uk
Atkinson
P F
PF
Hanger
D P
DP
Anderton
B H
BH
Daniel
S E
SE
Lantos
P L
PL
D000328:Adult; D000368:Aged; D000544:Alzheimer Disease / Q000473:pathology*; D000906:Antibodies; D015415:Biomarkers; D001921:Brain / Q000166:cytology / Q000473:pathology*; D001933:Brain Stem / Q000473:pathology; D002531:Cerebellum / Q000473:pathology; D005260:Female; D005625:Frontal Lobe / Q000473:pathology; D006624:Hippocampus / Q000473:pathology; D006801:Humans; D002479:Inclusion Bodies / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D016900:Neurofilament Proteins / Q000032:analysis; D009457:Neuroglia / Q000166:cytology / Q000473:pathology*; D010766:Phosphorylation; D012016:Reference Values; D013132:Spinocerebellar Degenerations / Q000473:pathology*; D016875:tau Proteins / Q000032:analysis*
D000906:Antibodies; D015415:Biomarkers; D016900:Neurofilament Proteins; D016875:tau Proteins