The extracellular chaperone clusterin sequesters oligomeric forms of the amyloid-beta 1-40 peptideFaculty of Science - Papers (Archive) (2012)
AbstractIn recent genome-wide association studies, the extracellular chaperone protein, clusterin, has been identified as a newly-discovered risk factor in Alzheimer's disease. We have examined the interactions between human clusterin and the Alzheimer's disease-associated amyloid-β 1-40 peptide (Aβ 1-40), which is prone to aggregate into an ensemble of oligomeric intermediates implicated in both the proliferation of amyloid fibrils and in neuronal toxicity. Using highly sensitive single-molecule fluorescence methods, we have found that Aβ 1-40 forms a heterogeneous distribution of small oligomers (from dimers to 50-mers), all of which interact with clusterin to form long-lived, stable complexes. Consequently, clusterin is able to influence both the aggregation and disaggregation of Aβ 1-40 by sequestration of the Aβ oligomers. These results not only elucidate the protective role of clusterin but also provide a molecular basis for the genetic link between clusterin and Alzheimer's disease.
Publication DateJanuary 1, 2012
Citation InformationPriyanka Narayan, Angel Orte, Richard W Clarke, Benedetta Bolognesi, et al.. "The extracellular chaperone clusterin sequesters oligomeric forms of the amyloid-beta 1-40 peptide" Faculty of Science - Papers (Archive) (2012)
Available at: http://works.bepress.com/mark_wilson/22/