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Positional effects of presenilin-1 mutations on tau phosphorylation in cortical plaques
Citation
Shepherd, CE and Gregory, GC and Vickers, JC and Brooks, WS and Kwok, JBJ and Schofield, PR and Kril, JJ and Halliday, GM, Positional effects of presenilin-1 mutations on tau phosphorylation in cortical plaques, Neurobiology of Disease, 15, (1) pp. 115-119. ISSN 0969-9961 (2004) [Refereed Article]
DOI: doi:10.1016/j.nbd.2003.10.008
Abstract
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. © 2003 Elsevier Inc. All rights reserved.
Item Details
Item Type: | Refereed Article |
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Research Division: | Biomedical and Clinical Sciences |
Research Group: | Neurosciences |
Research Field: | Neurology and neuromuscular diseases |
Objective Division: | Health |
Objective Group: | Clinical health |
Objective Field: | Clinical health not elsewhere classified |
UTAS Author: | Vickers, JC (Professor James Vickers) |
ID Code: | 32368 |
Year Published: | 2004 |
Web of Science® Times Cited: | 30 |
Deposited By: | Pathology |
Deposited On: | 2004-08-01 |
Last Modified: | 2005-05-27 |
Downloads: | 0 |
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