. Alzheimer's disease-affected brain: presence of oligomeric A beta ligands (ADDLs) suggests a molecular basis for reversible memory loss. Proc Natl Acad Sci U S A. 2003 Sep 2;100(18):10417-22. PubMed.


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  1. Small, soluble aggregates of the Aβ1-42 peptide are now believed to be the toxic factor that is responsible for synaptic dysfunction and eventual neuronal degeneration in Alzheimer's disease. This work adds to this consensus by showing that soluble extracts of brains from five cases of AD react with an antiserum specific for the Aβ1-42 peptide. Samples of both naturally derived Aβ1-42 peptides and synthetic versions were also found to bind in a punctate fashion to the external surfaces of culture hippocampal neurons. The authors suggest that Aβ oligomers might be binding to sites of signaling specializations, possibly related to synaptic terminals. To rule out non-specific binding, the Aβ oligomers were incubated with specific antibodies before adding them to the cultured cells. This blocked the binding of the added Aβ peptides to the cells, but this step in effect removed the oligomers from contact with the neurons and did not address whether oligomers that were available to the cells could bind non-specifically. It was also found, using the SDS gel overlay technique, that synthetic Aβ peptides bind to a number if unidentified proteins of hippocampal membrane fractions. While these preliminary observations are provocative, more direct evidence is needed to support the claim that oligomeric Aβ ligands bind in a biologically meaningful way to specific neuronal proteins that mediate signal transduction and that they are directly involved in reversible memory loss.