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...
| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2004-02-01
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| Series: | Neurobiology of Disease |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S0969996103002134 |
| id |
doaj-04390dca3802434183f5546b3ac6577e |
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| record_format |
Article |
| collection |
DOAJ |
| language |
English |
| format |
Article |
| sources |
DOAJ |
| author |
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 |
| spellingShingle |
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 Positional effects of presenilin-1 mutations on tau phosphorylation in cortical plaques Neurobiology of Disease Alzheimer's disease Presenilin Tau Phosphorylation Cotton wool plaques |
| author_facet |
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 |
| author_sort |
Claire E Shepherd |
| title |
Positional effects of presenilin-1 mutations on tau phosphorylation in cortical plaques |
| title_short |
Positional effects of presenilin-1 mutations on tau phosphorylation in cortical plaques |
| title_full |
Positional effects of presenilin-1 mutations on tau phosphorylation in cortical plaques |
| title_fullStr |
Positional effects of presenilin-1 mutations on tau phosphorylation in cortical plaques |
| title_full_unstemmed |
Positional effects of presenilin-1 mutations on tau phosphorylation in cortical plaques |
| title_sort |
positional effects of presenilin-1 mutations on tau phosphorylation in cortical plaques |
| publisher |
Elsevier |
| series |
Neurobiology of Disease |
| issn |
1095-953X |
| publishDate |
2004-02-01 |
| description |
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. |
| topic |
Alzheimer's disease Presenilin Tau Phosphorylation Cotton wool plaques |
| url |
http://www.sciencedirect.com/science/article/pii/S0969996103002134 |
| work_keys_str_mv |
AT claireeshepherd positionaleffectsofpresenilin1mutationsontauphosphorylationincorticalplaques AT gilliancgregory positionaleffectsofpresenilin1mutationsontauphosphorylationincorticalplaques AT jamescvickers positionaleffectsofpresenilin1mutationsontauphosphorylationincorticalplaques AT williamsbrooks positionaleffectsofpresenilin1mutationsontauphosphorylationincorticalplaques AT johnbjkwok positionaleffectsofpresenilin1mutationsontauphosphorylationincorticalplaques AT peterrschofield positionaleffectsofpresenilin1mutationsontauphosphorylationincorticalplaques AT jillianjkril positionaleffectsofpresenilin1mutationsontauphosphorylationincorticalplaques AT glendamhalliday positionaleffectsofpresenilin1mutationsontauphosphorylationincorticalplaques |
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doaj-04390dca3802434183f5546b3ac6577e2021-03-20T04:49:01ZengElsevierNeurobiology of Disease1095-953X2004-02-01151115119Positional effects of presenilin-1 mutations on tau phosphorylation in cortical plaquesClaire E Shepherd0Gillian C Gregory1James C Vickers2William S Brooks3John B.J Kwok4Peter R Schofield5Jillian J Kril6Glenda M Halliday7Prince 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, AustraliaPrince 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, AustraliaPrince 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, AustraliaPrince 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, AustraliaPrince 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, AustraliaPrince 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, AustraliaPrince 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, AustraliaPrince 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, AustraliaMutations 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.http://www.sciencedirect.com/science/article/pii/S0969996103002134Alzheimer's diseasePresenilinTauPhosphorylationCotton wool plaques |