Caspase-cleaved Tau-D421 iscolocalized with the immunophilin FKBP52 in the autophagy-endolysosomal system of Alzheimer’s disease neurons

Publication date: Available online 5 July 2016
Source:Neurobiology of Aging
Author(s): Geri Meduri, Kevin Guillemeau, Omar Dounane, Véronique Sazdovitch, Charles Duyckaerts, Béatrice Chambraud, Etienne Emile Baulieu, Julien Giustiniani
Pathological modifications of the Tau protein leading to neurofibrillary tangle (NFT) formation are a common feature of a wide range of neurodegenerative diseases known as tauopathies which include Alzheimer's disease (AD). We previously showed that the immunophilin FKBP52 physically and functionally interacts with Tau, and we recently reported that FKBP52 levels are abnormally low in AD patients brains. To decipher the mechanism of FKBP52 decrease in AD brains, we performed multiple labeling immunohistofluorescence and lysosomal purification using post-mortem brain samples of healthy controls (n=8) and AD (n=20) patients. Confocal analysis revealed that FKBP52 localizes to the endo-lysosomal system. We also report FKBP52 colocalization with the truncated Tau-D⁴²¹ in the autophagy-endolysosomal system in some AD neurons and that the decrease of FKBP52 correlates with NFT formation. Additional experiments of autophagy inhibition in Tau-inducible SH-SY5Y cells allowed demonstrating FKBP52 release in the extracellular milieu. Our findings point out the possibility that FKBP52 could be abnormally released from NFTs negative neurons in AD brains in correlation with the early pathological Tau-D⁴²¹ neuronal accumulation.

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