Aβ Oligomer-Induced Aberrations in Synapse Composition, Shape, and Density Provide a Molecular Basis for Loss of Connectivity in Alzheimer's Disease

The basis for memory loss in early Alzheimer's disease (AD) seems likely to involve synaptic damage caused by soluble Abeta-derived oligomers (ADDLs). ADDLs have been shown to build up in the brain and CSF of AD patients and are known to interfere with mechanisms of synaptic plasticity, acting as gain-of-function ligands that attach to synapses. Because of the correlation between AD dementia and synaptic degeneration, we investigated here the ability of ADDLs to affect synapse composition, structure, and abundance. Using highly differentiated cultures of hippocampal neurons, a preferred model for studies of synapse cell biology, we found that ADDLs bound to neurons with specificity, attaching to presumed…

• AH
  American Health Assistance Foundation
• ID
  Illinois Department of Public Health
• NU
  Northwestern University
• NI
  National Institutes of Health

  Awards: AG018877, AG022547