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Positional effects of presenilin-1 mutations on tau phosphorylation in cortical plaques
- Source :
-
Neurobiology of Disease . Feb2004, Vol. 15 Issue 1, p115. 5p. - Publication Year :
- 2004
-
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. [Copyright &y& Elsevier]
- Subjects :
- *GENETIC mutation
*ALZHEIMER'S disease
*MORPHOLOGY
*PHOSPHORYLATION
Subjects
Details
- Language :
- English
- ISSN :
- 09699961
- Volume :
- 15
- Issue :
- 1
- Database :
- Academic Search Index
- Journal :
- Neurobiology of Disease
- Publication Type :
- Academic Journal
- Accession number :
- 12037377
- Full Text :
- https://doi.org/10.1016/j.nbd.2003.10.008