Intracellular and secreted forms of clusterin are elevated early in Alzheimer's disease and associate with both Aβ and tau pathology

Abstract

Clusterin (CLU) is a pleiotropic glycoprotein that exists as a secreted, neuroprotective or intracellular, neurotoxic form, both of which increase in Alzheimer's disease (AD) causing increased Aβ42 deposition. No studies have assessed the association between functionally distinct alloforms of CLU and tau protein or neuronal loss, despite its intracellular toxicity. We confirm previous reports of significant increases in both intracellular CLU and secreted CLU in the brain tissue of individuals with AD (p < 0.01) and show no association with neuronal loss. The increase in CLU alloforms was most closely associated with increases in both insoluble Aβ42 and tau protein (p = 0.001), supporting its role in AD pathogenesis. Further research should investigate whether altering human CLU levels may have viability as a therapeutic option for AD.