title: Caspase-cleaved Tau-D(421) is colocalized with the immunophilin FKBP52 in the autophagy-endolysosomal system of Alzheimer's disease neurons.
abstract: Pathologic 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 postmortem brain samples of healthy controls (n = 8) and AD (n = 20) patients. Confocal analysis revealed that FKBP52 localizes to the endolysosomal system. We also report FKBP52 colocalization with the truncated Tau-D(421) 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 pathologic Tau-D(421) neuronal accumulation.
authors.affiliation: INSERM, Unité mixte de recherche 1195, Université Paris-Saclay, Le Kremlin Bicêtre, France.
authors.forename: Geri
authors.initials: G
authors.lastname: Meduri
authors.affiliation: INSERM, Unité mixte de recherche 1195, Université Paris-Saclay, Le Kremlin Bicêtre, France.
authors.forename: Kevin
authors.initials: K
authors.lastname: Guillemeau
authors.affiliation: INSERM, Unité mixte de recherche 1195, Université Paris-Saclay, Le Kremlin Bicêtre, France.
authors.forename: Omar
authors.initials: O
authors.lastname: Dounane
authors.affiliation: Laboratoire de Neuropathologie Escourolle, Hôpital de La Salpêtrière, AP-HP, Paris, France.
authors.forename: Véronique
authors.initials: V
authors.lastname: Sazdovitch
authors.affiliation: Laboratoire de Neuropathologie Escourolle, Hôpital de La Salpêtrière, AP-HP, Paris, France.
authors.forename: Charles
authors.initials: C
authors.lastname: Duyckaerts
authors.affiliation: INSERM, Unité mixte de recherche 1195, Université Paris-Saclay, Le Kremlin Bicêtre, France.
authors.forename: Béatrice
authors.initials: B
authors.lastname: Chambraud
authors.affiliation: INSERM, Unité mixte de recherche 1195, Université Paris-Saclay, Le Kremlin Bicêtre, France. Electronic address: etienne.baulieu@inserm.fr.
authors.forename: Etienne Emile
authors.initials: EE
authors.lastname: Baulieu
authors.affiliation: INSERM, Unité mixte de recherche 1195, Université Paris-Saclay, Le Kremlin Bicêtre, France. Electronic address: julien.giustiniani@inserm.fr.
authors.forename: Julien
authors.initials: J
authors.lastname: Giustiniani
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000235:genetics* / Q000378:metabolism*; D001343:Autophagy; D001921:Brain / Q000378:metabolism*; D020169:Caspases; D002478:Cells, Cultured; D005260:Female; D006801:Humans; D008247:Lysosomes / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D016874:Neurofibrillary Tangles / Q000378:metabolism / Q000473:pathology; D009474:Neurons / Q000166:cytology / Q000378:metabolism*; D022021:Tacrolimus Binding Proteins / Q000378:metabolism* / Q000502:physiology; D024801:Tauopathies / Q000235:genetics / Q000378:metabolism; D016875:tau Proteins / Q000378:metabolism*
chemical_list: D016875:tau Proteins; D020169:Caspases; D022021:Tacrolimus Binding Proteins; C403485:tacrolimus binding protein 4
keywords: Alzheimer disease; Autophagy; FKBP52; Lysosomes; Tau truncation; Tau-D(421)