Level of PICALM, a key component of clathrin-mediated endocytosis, is correlated with levels of phosphotau and autophagy-related proteins and is associated with tau inclusions in AD, PSP and Pick disease

NEUROBIOLOGY OF DISEASE

卷:94

Article

Ando, Kunie^1,2,3,4,5,6  Tomimura, Karen^1,2,3,4,5  Sazdovitch, Veronique¹  Suain, Valerie⁶  Yilmaz, Zehra⁶  Authelet, Michele⁶  Ndjim, Marieme^2,3,4,5  Vergara, Cristina⁶  Belkouch, Mounir^1,2,3,4,5  Potier, Marie-Claude^2,3,4,5  Duyckaerts, Charles^1,2,3,4,5  Brion, Jean-Pierre⁶ 

[1] Hop La Pitie Salpetriere, AP HP, Lab Neuropathol Escourolle, Blvd Hop 47-83, F-75651 Paris 13, France

[2] Univ Paris 06, Sorbonne Univ, UMR S 1127, F-75013 Paris, France

[3] INSERM, U 1127, F-75013 Paris, France

[4] CNRS UMR 7225, F-75013 Paris, France

[5] ICM, F-75013 Paris, France

[6] Univ Libre Bruxelles, UNI ULB Neurosci Inst, Lab Histol Neuroanat & Neuropathol, 808 Route Lennik,Bldg G, B-1070 Brussels, Belgium

关键词: PICALM;    Tau;    NFTs;    Alzheimer's disease;    Pick disease;    Progressive supranuclear palsy;    Corticobasal degeneration;    FTLD-MAPT;    FTLD-TDP;    Diffuse Lewy body disease;    Autophagy;    LC3;    Beclin-1;   

DOI  :  10.1016/j.nbd.2016.05.017

来源: Elsevier

【 摘 要 】

Single nucleotide polymorphisms in PICALM, a key component of clathrin-mediated endocytosis machinery, have been identified as genetic susceptibility loci for late onset Alzheimer's disease (LOAD). We previously reported that PICALM protein levels were decreased in AD brains and that PICALM was co-localised with neurofibrillary tangles in LOAD, familial AD with PSEN1 mutations and Down syndrome. In the present study, we analysed PICALM expression, cell localisation and association with pathological cellular inclusions in other tauopathies and in non-tau related neurodegenerative diseases. We observed that PICALM was associated with neuronal tau pathology in Pick disease and in progressive supranuclear palsy (PSP) and co-localised with both 3R and 4R tau positive inclusions unlike in corticobasal degeneration (CBD) or in frontotemporal lobar degeneration (FTLD)-MAPTP301L. PICALM immunoreactivities were not detected in tau-positive tufted astrocytes in PSP, astrocytic plaques in CBD, Lewy bodies in Lewy body disease, diffuse type (LBD) and in TDP-43-positive inclusions in FTLD. In the frontal cortex in tauopathies, the ratio of insoluble to soluble PICALM was increased while the level of soluble PICALM was decreased and was inversely correlated with the level of phosphotau. PICALM decrease was also significantly correlated with increased LC3-II and decreased Beclin-1 levels in tauopathies and in non-tau related neurodegenerative diseases. These results suggest that there is a close relationship between abnormal PICALM processing, tau pathology and impairment of autophagy in human neurodegenerative diseases. (C) 2016 Elsevier Inc. All rights reserved.

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