title: Alzheimer's disease: synaptic dysfunction and Abeta.
abstract: Synapse loss is an early and invariant feature of Alzheimer's disease (AD) and there is a strong correlation between the extent of synapse loss and the severity of dementia. Accordingly, it has been proposed that synapse loss underlies the memory impairment evident in the early phase of AD and that since plasticity is important for neuronal viability, persistent disruption of plasticity may account for the frank cell loss typical of later phases of the disease. Extensive multi-disciplinary research has implicated the amyloid beta-protein (Abeta) in the aetiology of AD and here we review the evidence that non-fibrillar soluble forms of Abeta are mediators of synaptic compromise. We also discuss the possible mechanisms of Abeta synaptotoxicity and potential targets for therapeutic intervention.
authors.affiliation: Center for Neurologic Diseases, Harvard Medical School and Brigham and Women's Hospital, Boston, MA, USA. gshankar1@partners.org.
authors.forename: Ganesh M
authors.initials: GM
authors.lastname: Shankar
authors.forename: Dominic M
authors.initials: DM
authors.lastname: Walsh