Review

Alzheimer's disease: synaptic dysfunction and Aβ

Ganesh M Shankar¹ and Dominic M Walsh²

• Corresponding authors: Ganesh M Shankar gshankar1@partners.org - Dominic M Walsh dominic.walsh@ucd.ie

Author Affiliations

¹ Center for Neurologic Diseases, Harvard Medical School and Brigham and Women's Hospital, Boston, MA, USA

² Laboratory for Neurodegenerative Research, The Conway Institute for Biomolecular and Biomedical Research, University College Dublin, Belfield, Dublin 4, Republic of Ireland

Molecular Neurodegeneration 2009, 4:48 doi:10.1186/1750-1326-4-48

Published: 23 November 2009

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 β-protein (Aβ) in the aetiology of AD and here we review the evidence that non-fibrillar soluble forms of Aβ are mediators of synaptic compromise. We also discuss the possible mechanisms of Aβ synaptotoxicity and potential targets for therapeutic intervention.