Abnormal tau phosphorylation in primary progressive multiple sclerosis

Jane Marian Anderson, Rickie Patani, Richard Reynolds, Richard Nicholas, Alastair Compston, Maria Grazia Spillantini, Siddharthan Chandran

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish
Pages (from-to)591-600
Number of pages10
JournalActa Neuropathologica
Volume119
Issue number5
DOIs
Publication statusPublished - May 2010

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