Clusterin in Alzheimer's disease: an amyloidogenic inhibitor of amyloid formation

Clusterin is a heterodimeric glycoprotein (- and {beta}-chain), which has been described as an extracellular molecular chaperone. In humans, clusterin is an amyloid associated protein, co-localizing with fibrillar deposits in several amyloidoses, including Alzheimers disease. To clarify its potential implication in amyloid formation, we located aggregation-prone regions within the sequence of clusterin -chain, via computational methods. We had peptide-analogues of each region chemically synthesized and experimentally demonstrated that all of them can form amyloid-like fibrils. We also provide evidence that the same peptide-analogues can inhibit amyloid-{beta} fibril formation. These findings elucidate parts of the molecular mechanism in which clusterin inhibits amyloid formation. At the same time, they hint that molecular chaperones with amyloidogenic properties might have a role in the regulation of amyloid formation, essentially acting as functional amyloids.