title: Decrease of the immunophilin FKBP52 accumulation in human brains of Alzheimer's disease and FTDP-17.
abstract: Human neurodegenerative diseases characterized by abnormal intraneuronal inclusions of the tau protein, or "tauopathies", include Alzheimer's disease (AD), Pick's disease, progressive supranuclear palsy, corticobasal degeneration as well as fronto-temporal dementia and Parkinsonism linked to chromosome 17 (FTDP-17). Several abnormalities of tau may contribute to the pathological processes, yet the mechanisms involved in tau cellular toxicity remain unclear. Previously, we demonstrated an interaction between various isoforms of tau and the immunophilin FKBP52 (FK506-Binding Protein), suggesting a direct involvement of FKBP52 in tau function. Here we analyze the expression of FKBP52 in human brains of patients with different tauopathies, including AD. Immunohistofluorescence studies carried out on cerebral cortex in different tauopathies reveal that FKBP52 is not sequestered by filamentous tau inclusions while FKBP52 is colocalized with tau in the control case brains. We found that FKBP52 expression level is abnormally low in frontal cortex of AD and FTDP-17 brains, as compared to controls, despite no alteration in the FKBP52 mRNA expression level. The possible involvement of FKBP52 in pathological tau expression/function is discussed.
authors.affiliation: Institut National de la Santé et de la Recherche Médicale U788, Stéroïdes et Systèmes Nerveux, Le Kremlin-Bicêtre Cedex, France.
authors.forename: Julien
authors.initials: J
authors.lastname: Giustiniani
authors.forename: Marlène
authors.initials: M
authors.lastname: Sineus
authors.forename: Elodie
authors.initials: E
authors.lastname: Sardin
authors.forename: Omar
authors.initials: O
authors.lastname: Dounane
authors.forename: Maï
authors.initials: M
authors.lastname: Panchal
authors.forename: Véronique
authors.initials: V
authors.lastname: Sazdovitch
authors.forename: Charles
authors.initials: C
authors.lastname: Duyckaerts
authors.forename: Béatrice
authors.initials: B
authors.lastname: Chambraud
authors.forename: Etienne-Emile
authors.initials: EE
authors.lastname: Baulieu
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D001921:Brain / Q000378:metabolism*; D005260:Female; D057180:Frontotemporal Dementia / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D005786:Gene Expression Regulation / Q000502:physiology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D016874:Neurofibrillary Tangles / Q000473:pathology; D012333:RNA, Messenger / Q000378:metabolism; D022021:Tacrolimus Binding Proteins / Q000235:genetics / Q000378:metabolism*; D016875:tau Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: C054369:MAPT protein, human; D012333:RNA, Messenger; D016875:tau Proteins; D022021:Tacrolimus Binding Proteins; C403485:tacrolimus binding protein 4