title: Alzheimer brain-derived amyloid β-protein impairs synaptic remodeling and memory consolidation.
abstract: Aggregation of the amyloid β-protein (Aβ) is believed to play a central role in initiating the molecular cascade that culminates in Alzheimer-type dementia (AD), a disease which in its early stage is characterized by synaptic loss and impairment of episodic memory. Here we show that intracerebroventricular injection of Aβ-containing water-soluble extracts of AD brain inhibits consolidation of the memory of avoidance learning in the rat and that this effect is highly dependent on the interval between learning and administration. When injected at 1 hour post training extracts from 2 different AD brains significantly impaired recall tested at 48 hours. Ultrastructural examination of hippocampi from animals perfused after 48 hours revealed that Aβ-mediated impairment of avoidance memory was associated with lower density of synapses and altered synaptic structure in the dentate gyrus and CA1 fields. These behavioral and ultrastructural data suggest that human brain-derived Aβ impairs formation of long-term memory by compromising the structural plasticity essential for consolidation and that Aβ targets processes initiated very early in the consolidation pathway.
authors.affiliation: Laboratory for Neurodegenerative Research, School of Biomolecular and Biomedical Science, Conway Institute, University College Dublin, Dublin, Republic of Ireland.
authors.forename: Gilyana G
authors.initials: GG
authors.lastname: Borlikova
authors.forename: Margarita
authors.initials: M
authors.lastname: Trejo
authors.forename: Alexandra J
authors.initials: AJ
authors.lastname: Mably
authors.forename: Jessica M
authors.initials: JM
authors.lastname: Mc Donald
authors.forename: Carlo
authors.initials: C
authors.lastname: Sala Frigerio
authors.forename: Ciaran M
authors.initials: CM
authors.lastname: Regan
authors.forename: Keith J
authors.initials: KJ
authors.lastname: Murphy
authors.forename: Eliezer
authors.initials: E
authors.lastname: Masliah
authors.forename: Dominic M
authors.initials: DM
authors.lastname: Walsh
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000378:metabolism*; D016229:Amyloid beta-Peptides / Q000378:metabolism* / Q000494:pharmacology*; D000818:Animals; D001362:Avoidance Learning / Q000187:drug effects*; D001921:Brain / Q000378:metabolism*; D005260:Female; D006801:Humans; D008297:Male; D061212:Memory, Episodic; D009473:Neuronal Plasticity / Q000187:drug effects*; D051381:Rats; D017208:Rats, Wistar; D009435:Synaptic Transmission / Q000187:drug effects*
chemical_list: D016229:Amyloid beta-Peptides