Document Detail


SAP97-mediated local trafficking is altered in Alzheimer disease patients' hippocampus.
MedLine Citation:
PMID:  20980075     Owner:  NLM     Status:  In-Data-Review    
Abstract/OtherAbstract:
Synapse-asssociated protein-97 (SAP97) is responsible for the trafficking of both glutamate receptor subunits, GluR1 and NR2A, and α-secretase ADAM10 to the synaptic membrane. Here we evaluate the trafficking capability of SAP97 in Alzheimer disease (AD) patients' brain. We analyzed autoptic hippocampus and superior frontal gyrus, respectively as an affected and a less affected area, from 6 AD patients (Braak 4) and 6 healthy controls. In hippocampus, but not in superior frontal gyrus, of AD patients, ADAM10 and GluR1 synaptic membrane levels are altered while NR2A localization is not affected. Both immunoprecipitation and pull-down assays demonstrated that SAP97 failed to correctly couple to ADAM10 and GluR1, but not to NR2A. These findings not only indicate SAP97 as a point of convergence between amyloid cascade and synaptic failure in AD, but also allow a different interpretation of AD which can be now perceived as synaptic trafficking defect pathology.
Authors:
Elena Marcello; Roberta Epis; Claudia Saraceno; Fabrizio Gardoni; Barbara Borroni; Flaminio Cattabeni; Alessandro Padovani; Monica Di Luca
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Publication Detail:
Type:  Journal Article     Date:  2010-10-27
Journal Detail:
Title:  Neurobiology of aging     Volume:  33     ISSN:  1558-1497     ISO Abbreviation:  Neurobiol. Aging     Publication Date:  2012 Feb 
Date Detail:
Created Date:  2011-12-05     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  8100437     Medline TA:  Neurobiol Aging     Country:  United States    
Other Details:
Languages:  eng     Pagination:  422.e1-422.e10     Citation Subset:  IM    
Copyright Information:
Copyright © 2012 Elsevier Inc. All rights reserved.
Affiliation:
Università degli Studi di Milano, Department of Pharmacological Sciences and Centre of Excellence on Neurodegenerative Diseases, Milan, Italy.
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