title: SAP97-mediated local trafficking is altered in Alzheimer disease patients' hippocampus.
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.
authors.affiliation: Università degli Studi di Milano, Department of Pharmacological Sciences and Centre of Excellence on Neurodegenerative Diseases, Milan, Italy.
authors.forename: Elena
authors.initials: E
authors.lastname: Marcello
authors.forename: Roberta
authors.initials: R
authors.lastname: Epis
authors.forename: Claudia
authors.initials: C
authors.lastname: Saraceno
authors.forename: Fabrizio
authors.initials: F
authors.lastname: Gardoni
authors.forename: Barbara
authors.initials: B
authors.lastname: Borroni
authors.forename: Flaminio
authors.initials: F
authors.lastname: Cattabeni
authors.forename: Alessandro
authors.initials: A
authors.lastname: Padovani
authors.forename: Monica
authors.initials: M
authors.lastname: Di Luca
mesh_terms: D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000378:metabolism*; D001921:Brain / Q000378:metabolism*; D005260:Female; D006624:Hippocampus / Q000378:metabolism*; D006801:Humans; D008297:Male; D021381:Protein Transport; D013569:Synapses / Q000378:metabolism*; D014018:Tissue Distribution