Protein markers for Alzheimer disease in the frontal cortex and cerebellum1

Détails

ID Serval
serval:BIB_158922A01D0B
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Institution
Titre
Protein markers for Alzheimer disease in the frontal cortex and cerebellum1
Périodique
Neurology
Auteur(s)
Verdile  G., Gnjec  A., Miklossy  J., Fonte  J., Veurink  G., Bates  K., Kakulas  B., Mehta  P. D., Milward  E. A., Tan  N., Lareu  R., Lim  D., Dharmarajan  A., Martins  R. N.
ISSN
1526-632X (Electronic)
Statut éditorial
Publié
Date de publication
2004
Volume
63
Numéro
8
Pages
1385-1392
Notes
PT - Comparative Study PT - Journal Article PT - Research Support, Non-U.S. Gov't PT - Research Support, U.S. Gov't, Non-P.H.S
Résumé
OBJECTIVE: To compare proteins related to Alzheimer disease (AD) in the frontal cortex and cerebellum of subjects with early-onset AD (EOAD) with or without presenilin 1 (PS1) mutations with sporadic late-onset AD (LOAD) and nondemented control subjects. METHODS: Immunohistochemistry, immunoblot analysis, and ELISA were used to detect and assess protein levels in brain. RESULTS: In EOAD and to a lesser extent in LOAD, there was increased amyloid beta (Abeta) deposition (by immunohistochemistry), increased soluble Abeta (by immunoblot analysis), and specific increases in Abeta40 and Abeta42 (by ELISA) in the frontal cortex and, in some cases, in the cerebellum. Surprisingly, immunoblot analysis revealed reduced levels of PS1 in many of the subjects with EOAD with or without PS1 mutations. In those PS1 mutation-bearing subjects with the highest Abeta, PS1 was barely, if at all, detectable. This decrease in PS1 was specific and not attributable solely to neuronal loss because amyloid precursor protein (APP) and the PS1-interacting protein beta-catenin levels were unchanged. CONCLUSIONS: This study shows that in the frontal cortex and cerebellum from Alzheimer disease patients harboring certain presenilin 1 mutations, high levels of amyloid beta are associated with low levels of presenilin 1. The study provides the premise for further investigation of mechanisms underlying the downregulation of presenilin 1, which may have considerable pathogenic and therapeutic relevance
Mots-clé
Adult/Aged/Aged,80 and over/Alzheimer Disease/Amyloid beta-Protein/analysis/beta Catenin/Biological Markers/Brain/Cerebellum/Disease/Down-Regulation/Enzyme-Linked Immunosorbent Assay/Female/Frontal Lobe/genetics/Humans/Immunohistochemistry/Male/Membrane Proteins/metabolism/methods/Middle Aged/Mutation/Pathology/Peptide Fragments/physiology/physiopathology/Presenilin-1/Proteins/Research/Up-Regulation
Pubmed
Web of science
Création de la notice
29/01/2008 18:36
Dernière modification de la notice
20/08/2019 12:44
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