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 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
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