title: Alzheimer's disease protein Abeta1-42 does not disrupt isolated synaptic vesicles.
abstract: Synaptic vesicles are central to neurotransmission and cognition. Studies of the Alzheimer's disease (AD) associated peptide, amyloid beta (Abeta), suggest that it has the potential to non-specifically solubilize or permeabilize membranes and that it has detergent and pore-forming properties. Damage to the membrane or integrity of synaptic vesicles could compromise its function. We test the hypothesis that the intact synaptic vesicle is a direct site of attack by Abeta1-42 in AD pathology by examining the properties of individual isolated vesicles exposed to Abeta1-42. In particular, we compared the rate of leakage of dye molecules from synaptic vesicles, the rate of proton permeation across the membrane of the vesicle, and the rate of active proton transport into the vesicle interior in the presence and absence of Abeta1-42. From these experiments, we conclude that isolated synaptic vesicles are not disrupted by Abeta1-42.
authors.affiliation: University of Washington, Department of Chemistry, Box 351700, Seattle, WA 98195, USA.
authors.forename: Peter B
authors.initials: PB
authors.lastname: Allen
authors.forename: Daniel T
authors.initials: DT
authors.lastname: Chiu
mesh_terms: D000255:Adenosine Triphosphate / Q000494:pharmacology; D000544:Alzheimer Disease / Q000378:metabolism* / Q000473:pathology; D016229:Amyloid beta-Peptides / Q000494:pharmacology*; D000818:Animals; D005456:Fluorescent Dyes / Q000378:metabolism; D006863:Hydrogen-Ion Concentration / Q000187:drug effects; D007425:Intracellular Membranes / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D044085:Microfluidics; D008856:Microscopy, Fluorescence; D010446:Peptide Fragments / Q000494:pharmacology*; D010477:Perfusion; D051381:Rats; D013572:Synaptic Vesicles / Q000187:drug effects* / Q000378:metabolism; D016708:Synaptophysin / Q000378:metabolism
chemical_list: D016229:Amyloid beta-Peptides; D005456:Fluorescent Dyes; D010446:Peptide Fragments; D016708:Synaptophysin; C075222:amyloid beta-protein (1-42); D000255:Adenosine Triphosphate