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

Claire E Shepherd; Gillian C Gregory; James C Vickers; William S Brooks; John B.J Kwok; Peter R Schofield; Jillian J Kril; Glenda M Halliday

Neurobiology of Disease (Feb 2004)

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

Claire E Shepherd,
Gillian C Gregory,
James C Vickers,
William S Brooks,
John B.J Kwok,
Peter R Schofield,
Jillian J Kril,
Glenda M Halliday

Affiliations

Claire E Shepherd: Prince of Wales Medical Research Institute, Randwick, Sydney 2031, Australia; Centre for Education and Research on Ageing, The University of Sydney, Concord Hospital, Concord 2139, Australia; The University of New South Wales, Sydney 2052, Australia; Discipline of Pathology, University of Tasmania, Hobart, Tasmania 7000, Australia; Garvan Institute of Medical Research, Sydney 2010, Australia
Gillian C Gregory: Prince of Wales Medical Research Institute, Randwick, Sydney 2031, Australia; Centre for Education and Research on Ageing, The University of Sydney, Concord Hospital, Concord 2139, Australia; The University of New South Wales, Sydney 2052, Australia; Discipline of Pathology, University of Tasmania, Hobart, Tasmania 7000, Australia; Garvan Institute of Medical Research, Sydney 2010, Australia
James C Vickers: Prince of Wales Medical Research Institute, Randwick, Sydney 2031, Australia; Centre for Education and Research on Ageing, The University of Sydney, Concord Hospital, Concord 2139, Australia; The University of New South Wales, Sydney 2052, Australia; Discipline of Pathology, University of Tasmania, Hobart, Tasmania 7000, Australia; Garvan Institute of Medical Research, Sydney 2010, Australia
William S Brooks: Prince of Wales Medical Research Institute, Randwick, Sydney 2031, Australia; Centre for Education and Research on Ageing, The University of Sydney, Concord Hospital, Concord 2139, Australia; The University of New South Wales, Sydney 2052, Australia; Discipline of Pathology, University of Tasmania, Hobart, Tasmania 7000, Australia; Garvan Institute of Medical Research, Sydney 2010, Australia
John B.J Kwok: Prince of Wales Medical Research Institute, Randwick, Sydney 2031, Australia; Centre for Education and Research on Ageing, The University of Sydney, Concord Hospital, Concord 2139, Australia; The University of New South Wales, Sydney 2052, Australia; Discipline of Pathology, University of Tasmania, Hobart, Tasmania 7000, Australia; Garvan Institute of Medical Research, Sydney 2010, Australia
Peter R Schofield: Prince of Wales Medical Research Institute, Randwick, Sydney 2031, Australia; Centre for Education and Research on Ageing, The University of Sydney, Concord Hospital, Concord 2139, Australia; The University of New South Wales, Sydney 2052, Australia; Discipline of Pathology, University of Tasmania, Hobart, Tasmania 7000, Australia; Garvan Institute of Medical Research, Sydney 2010, Australia
Jillian J Kril: Prince of Wales Medical Research Institute, Randwick, Sydney 2031, Australia; Centre for Education and Research on Ageing, The University of Sydney, Concord Hospital, Concord 2139, Australia; The University of New South Wales, Sydney 2052, Australia; Discipline of Pathology, University of Tasmania, Hobart, Tasmania 7000, Australia; Garvan Institute of Medical Research, Sydney 2010, Australia
Glenda M Halliday: Prince of Wales Medical Research Institute, Randwick, Sydney 2031, Australia; Centre for Education and Research on Ageing, The University of Sydney, Concord Hospital, Concord 2139, Australia; The University of New South Wales, Sydney 2052, Australia; Discipline of Pathology, University of Tasmania, Hobart, Tasmania 7000, Australia; Garvan Institute of Medical Research, Sydney 2010, Australia

Journal volume & issue: Vol. 15, no. 1
pp. 115 – 119

Abstract

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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.

Published in Neurobiology of Disease

ISSN: 0969-9961 (Print); 1095-953X (Online)
Publisher: Elsevier
Country of publisher: United States
LCC subjects: Medicine: Internal medicine: Neurosciences. Biological psychiatry. Neuropsychiatry
Website: https://www.journals.elsevier.com/neurobiology-of-disease

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