The heat shock response in FAP: the role of the extracellular chaperone clusterin.

Extracellular chaperones, such as clusterin, have been proposed to contribute to extracellular protein homeostasis. In Alzheimer's disease (AD), clusterin was suggested to be involved in fibrillogenesis and extracellular misfolded protein clearance. Here, we study the relevance of clusterin in familial amyloidotic polyneuropathy (FAP). Analysis of clusterin levels by ELISA showed decreased levels in asymptomatic and in FAP patients, which could be regarded as a consequence of clusterin mobilization to tissues. Incubation of a neuroblastoma cell line with transthyretin (TTR) oligomers resulted in secretion of clusterin into the media and binding to oligomeric species, not observed in parallel experiments with soluble TTR. Overall, our results allow us to postulate a putative protective role of clusterin in FAP, namely in the modulation of TTR aggregate formation. Future experiments are required to clarify the role of clusterin in FAP.