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The presynaptic lipid phosphatase Synaptojanin1 shows increased insolubility in Alzheimer brains, is localized with Hirano bodies and accumulated in plaque-associated dystrophic neurites.

Kunie Ando1*, Marième Ndjim2, Gustavo Pregoni2, Luce Dauphinot2, Gaëlle Fontaine2, Zehra Yilmaz1, Valérie Suain1, Robert De Decker1, Michèle Authelet1, Benoit Delatour2*, Charles DUYCKAERTS2, 3, Jean-Pierre Brion1 and Marie-Claude Potier2
  • 1 Laboratory of Histology, Neuroanatomy and Neuropathology, ULB Neuroscience Institute (UNI), Faculty of Medicine, Université Libre de Bruxelles, Belgium
  • 2 INSERM U1127 Institut du Cerveau et de la Moelle épinière, France
  • 3 Laboratoire de Neuropathologie Escourolle, Hôpital de la Pitié-Salpêtrière, AP-HP, France

Synaptojanin1 (SYNJ1) is a brain-enriched lipid phosphatase encoded by a gene on human chromosome 21, involved in autophagosomal/endosomal trafficking and synaptic vesicle recycling. Its dysfunction has been implicated in several neurodegenerative diseases, including Alzheimer disease (AD) and Down syndrome. Its level and cellular localization in AD brain tissue remains however elusive. We have compared in two large cohorts of controls and AD patients the expression levels and the cellular localization of SYNJI and its association with neuropathological lesions. We report here that SYNJ1 was co-localized with actin in Hirano bodies in the hippocampal pyramidal neurons in AD. SYNJ1 immunoreactive granular structures were approximately surrounded by, and sometimes co-localized with, hyperphosphorylated tau in pre-tangles and NFTs. SYNJ1 immunoreactivity was also found in the dystrophic neurites surrounding amyloid plaques. SYNJ1 transcripts were significantly increased in AD T1 isocortex and this increase had a significant association with the presence of APOε4 allele(s) but not with age. Biochemical analyses indicated that SYNJ1 undergoes a significant decrease in solubility in AD isocortex. Taken together, this study provides the first histological and biochemical evidence of mislocalization and misregulation of SYNJ1 in AD brains, and suggests that these changes contribute to the documented endocytosis/autophagy impairment and synaptic dysfunction in AD.

Acknowledgements

The brain tissues were provided by the GIE NeuroCEB brain bank (France Alzheimer, France Parkinson, ARSEP, CSC) and LHNN brain bank at ULB. J.P.B was supported by grants from the Belgian Fonds de la Recherche Scientifique Médicale (T.0023.15), the Aline Fund (King Baudoin Foundation), the Foundation for Alzheimer Research (FRA/SAO), the Génicot Fund and the research was performed in the frame of the IAP program (P7/16) of the Belgian Federal Science Policy Office.

Keywords: Synaptojanin1/synj1, tau, Amyloid, Hirano bodies, Alzheimer ' s disease, Neurofibrillary tangle (NFT)

Conference: Belgian Brain Congress 2018 — Belgian Brain Council, LIEGE, Belgium, 19 Oct - 19 Oct, 2018.

Presentation Type: e-posters

Topic: NOVEL STRATEGIES FOR NEUROLOGICAL AND MENTAL DISORDERS: SCIENTIFIC BASIS AND VALUE FOR PATIENT-CENTERED CARE

Citation: Ando K, Ndjim M, Pregoni G, Dauphinot L, Fontaine G, Yilmaz Z, Suain V, De Decker R, Authelet M, Delatour B, DUYCKAERTS C, Brion J and Potier M (2019). The presynaptic lipid phosphatase Synaptojanin1 shows increased insolubility in Alzheimer brains, is localized with Hirano bodies and accumulated in plaque-associated dystrophic neurites.. Front. Neurosci. Conference Abstract: Belgian Brain Congress 2018 — Belgian Brain Council. doi: 10.3389/conf.fnins.2018.95.00010

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Received: 01 Aug 2018; Published Online: 17 Jan 2019.

* Correspondence:
Dr. Kunie Ando, Laboratory of Histology, Neuroanatomy and Neuropathology, ULB Neuroscience Institute (UNI), Faculty of Medicine, Université Libre de Bruxelles, Brussels, Belgium, kunie29@yahoo.co.jp
Dr. Benoit Delatour, INSERM U1127 Institut du Cerveau et de la Moelle épinière, Paris, Île-de-France, 75013, France, benoit.delatour@upmc.fr