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

Biochim Biophys Acta Mol Basis Dis. 2022 Jul 1;1868(7):166384. doi: 10.1016/j.bbadis.2022.166384. Epub 2022 Mar 13.


Clusterin is a heterodimeric glycoprotein (α- and β-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 Alzheimer's disease. To clarify its potential implication in amyloid formation, we located aggregation-prone regions within the sequence of clusterin α-chain, via computational methods. We had peptide-analogues, which correspond to each of these regions, 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-β fibril formation, potentially making them appropriate drug candidates for Alzheimer's disease. At the same time, our findings hint that the respective aggregation-prone clusterin regions may be implicated in the molecular mechanism in which clusterin inhibits amyloid formation. Furthermore, we suggest that molecular chaperones with amyloidogenic properties might have a role in the regulation of amyloid formation, essentially acting as functional amyloids.

Keywords: Aggregation-prone regions; Alzheimer's disease; Amyloid; Amyloid inhibitors; Amyloid-β; Clusterin.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alzheimer Disease* / drug therapy
  • Alzheimer Disease* / metabolism
  • Amyloid / metabolism
  • Amyloidosis* / drug therapy
  • Clusterin / chemistry
  • Clusterin / metabolism
  • Clusterin / pharmacology
  • Glycoproteins
  • Humans


  • Amyloid
  • Clusterin
  • Glycoproteins