Review

Alzheimer's disease: synapses gone cold

Robert M Koffie^1,2, Bradley T Hyman¹ and Tara L Spires-Jones^1*

• * Corresponding author: Tara L Spires-Jones tspires@partners.org

Author Affiliations

¹ Massachusetts General Hospital, Harvard Medical School, 114 16th Street, Charlestown, MA 02129, USA

² Harvard Biophysics Program, Building C-2, room 122, 240 Longwood Ave, Boston, MA 02115, USA

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Molecular Neurodegeneration 2011, 6:63 doi:10.1186/1750-1326-6-63

Published: 26 August 2011

Abstract

Alzheimer's disease (AD) is a progressive neurodegenerative disease characterized by insidious cognitive decline and memory dysfunction. Synapse loss is the best pathological correlate of cognitive decline in AD and mounting evidence suggests that AD is primarily a disease of synaptic dysfunction. Soluble oligomeric forms of amyloid beta (Aβ), the peptide that aggregates to form senile plaques in the brain of AD patients, have been shown to be toxic to neuronal synapses both in vitro and in vivo. Aβ oligomers inhibit long-term potentiation (LTP) and facilitate long-term depression (LTD), electrophysiological correlates of memory formation. Furthermore, oligomeric Aβ has also been shown to induce synapse loss and cognitive impairment in animals. The molecular underpinnings of these observations are now being elucidated, and may provide clear therapeutic targets for effectively treating the disease. Here, we review recent findings concerning AD pathogenesis with a particular focus on how Aβ impacts synapses.