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

SAP97-mediated local trafficking is altered in Alzheimer disease patients' hippocampus / E. Marcello, R. Epis, C. Saraceno, F. Gardoni, B. Borroni, F. Cattabeni, A. Padovani, M. DiLuca. - In: NEUROBIOLOGY OF AGING. - ISSN 0197-4580. - 33:2(2012), pp. 422.e1-422.e10.

SAP97-mediated local trafficking is altered in Alzheimer disease patients' hippocampus

E. Marcello
Primo
;
R. Epis
Secondo
;
C. Saraceno;F. Gardoni;F. Cattabeni;M. DiLuca
Ultimo
2012

Abstract

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
Alzheimer Disease ; Scaffolding proteins ; ADAM10 ; AMPA receptor ; NMDA receptor ; Glutamatergic synapse
Settore BIO/14 - Farmacologia
2012
Article (author)
File in questo prodotto:
File Dimensione Formato  
1-s2.0-S0197458010003957-main.pdf

accesso aperto

Tipologia: Publisher's version/PDF
Dimensione 1.38 MB
Formato Adobe PDF
1.38 MB Adobe PDF Visualizza/Apri
Pubblicazioni consigliate

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2434/162387
Citazioni
  • ???jsp.display-item.citation.pmc??? 20
  • Scopus 47
  • ???jsp.display-item.citation.isi??? 46
social impact