Evidence for abnormal tau phosphorylation in early aggressive multiple sclerosis.
Although progression in multiple sclerosis is pathologically dominated by neurodegeneration, the underlying mechanism is unknown. Abnormal hyperphosphorylation of tau is implicated in the aetiopathogenesis of some common neurodegenerative disorders. We recently demonstrated the association of insoluble tau with established secondary progressive MS, raising the hypothesis that its accumulation is relevant to disease progression. In order to begin to determine the temporal emergence of abnormal tau with disease progression in MS, we examined tau phosphorylation in cerebral tissue from a rare case of early aggressive MS. We report tau hyperphosphorylation occurring in multiple cell types, with biochemical analysis confirming restriction to the soluble fraction. The absence of sarcosyl-insoluble tau fraction in early disease and its presence in secondary progression raises the possibility that insoluble tau accumulates with disease progression.
Anderson
Jane Marian
JM
Cambridge Centre for Brain Repair, Department of Clinical Neurosciences, University of Cambridge, Forvie Site, Robinson Way, Cambridge, UK.
Patani
Rickie
R
Reynolds
Richard
R
Nicholas
Richard
R
Compston
Alastair
A
Spillantini
Maria Grazia
MG
Chandran
Siddharthan
S
D000328:Adult; D001921:Brain / Q000378:metabolism* / Q000473:pathology; D018450:Disease Progression; D005260:Female; D006801:Humans; D009103:Multiple Sclerosis / Q000378:metabolism* / Q000473:pathology; D010766:Phosphorylation; D012720:Severity of Illness Index; D013997:Time Factors; D016875:tau Proteins / Q000378:metabolism*
D016875:tau Proteins