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Abnormal tau phosphorylation in primary progressive multiple sclerosis.

TitleAbnormal tau phosphorylation in primary progressive multiple sclerosis.
Publication TypeJournal Article
Year of Publication2010
AuthorsAnderson JMarian, Patani R, Reynolds R, Nicholas R, Compston A, Spillantini MGrazia, Chandran S
JournalActa Neuropathol
Volume119
Issue5
Pagination591-600
Date Published2010 May
ISSN1432-0533
KeywordsAdult, Aged, Blotting, Western, Brain, Disease Progression, Female, Humans, Immunohistochemistry, Male, Microscopy, Confocal, Middle Aged, Multiple Sclerosis, Chronic Progressive, Neuroglia, Neurons, Phosphorylation, Severity of Illness Index, tau Proteins
Abstract

Although neurodegeneration is the pathological substrate of progression in multiple sclerosis (MS), the underlying mechanisms remain unresolved. Abnormal phosphorylation of tau, implicated in the aetiopathogenesis of a number of classic neurodegenerative disorders, has also recently been described in secondary progressive MS (SPMS). In contrast to SPMS, primary progressive MS (PPMS) represents a significant subset of patients with accumulating neurological disability from onset. The neuropathological relationship between SPMS and PPMS is unknown. Against this background, we investigated tau phosphorylation status in five cases of PPMS using immunohistochemical and biochemical methods. We report widespread abnormal tau hyperphosphorylation of the classic tau phospho-epitopes occurring in multiple cell types but with a clear immunohistochemical glial bias. In addition, biochemical analysis revealed abnormally phosphorylated insoluble tau in all cases. These findings establish a platform for further study of the role of insoluble tau formation, including determining the relevance of glial tau pathology, in the neurodegenerative phase of MS.

DOI10.1007/s00401-010-0671-4
Alternate JournalActa Neuropathol.
PubMed ID20306268
Grant ListG0700356 / / Medical Research Council / United Kingdom
/ / Medical Research Council / United Kingdom
/ / Wellcome Trust / United Kingdom