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Positional effects of presenilin-1 mutations on tau phosphorylation in cortical plaques


Mutations in presenilin-1 (PS-1) account for the majority of familial Alzheimer's disease (AD). While increasing Abeta42 is one mechanism whereby PS-1 mutations are thought to exert their pathogenic effect, little is known about the role of tau in PS-1 AD. This study compares staining (AT8 and tau-2), morphology and quantity of tau-immunoreactive cortical plaques in six PS-1 and five sporadic AD cases. The densities of tau-positive plaques differentiated PS-1 from sporadic AD cases. All PS-1 cases demonstrated a greater than 6-fold increase in tau-2-positive plaques. In PS-1 cases with mutations in exons 5 and 6, there was an increase in classical AD plaques containing hyperphosphorylated tau (AT8- and tau 2-positive). However, cases with exon 8 and 9 mutations had numerous cotton wool plaques containing nonhyperphosphorylated tau (tau-2-positive, AT8-negative). These findings suggest that PS-1 mutations increase tau deposition while mutation-specific cellular responses determine phosphorylation events and may influence cell death mechanisms.

Type Journal
ISBN 0969-9961 (Print)
Authors Shepherd, C. E.;Gregory, G. C.;Vickers, J. C.;Brooks, W. S.;Kwok, J. B.;Schofield, P. R.;Kril, J. J.;Halliday, G. M. :
Published Date 2004-01-01
Published Volume 15
Published Issue 1
Published Pages 115-9
Status Published in-print
URL link to publisher's version