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

Elena Marcello, Roberta Epis, Claudia Saraceno, Fabrizio Gardoni, Barbara Borroni, Flaminio Cattabeni, Alessandro Padovani, Monica di Luca

Research output: Contribution to journalArticle

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.

Original languageEnglish
JournalNeurobiology of Aging
Volume33
Issue number2
DOIs
Publication statusPublished - Feb 2012

Keywords

  • ADAM10
  • Alzheimer disease
  • AMPA receptor
  • Glutamatergic synapse
  • NMDA receptor
  • Scaffolding proteins

ASJC Scopus subject areas

  • Clinical Neurology
  • Neuroscience(all)
  • Ageing
  • Developmental Biology
  • Geriatrics and Gerontology

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