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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
Research Division:Medical and Health Sciences
Research Group:Neurosciences
Research Field:Neurology and Neuromuscular Diseases
Objective Division:Health
Objective Group:Clinical Health (Organs, Diseases and Abnormal Conditions)
Objective Field:Nervous System and Disorders
Author:Vickers, JC (Professor James Vickers)
ID Code:32368
Year Published:2004
Web of Science® Times Cited:28
Deposited By:Pathology
Deposited On:2004-08-01
Last Modified:2005-05-27
Downloads:0

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