Please use this identifier to cite or link to this item: https://ahro.austin.org.au/austinjspui/handle/1/22171
Title: Decrease in p3-Alcβ37 and p3-Alcβ40, products of Alcadein β generated by γ-secretase cleavages, in aged monkeys and patients with Alzheimer's disease.
Austin Authors: Hata, Saori;Omori, Chiori;Kimura, Ayano;Saito, Haruka;Kimura, Nobuyuki;Gupta, Veer;Pedrini, Steve;Hone, Eugene;Chatterjee, Pratishtha;Taddei, Kevin;Kasuga, Kensaku;Ikeuchi, Takeshi;Waragai, Masaaki;Nishimura, Masaki;Hu, Anqi;Nakaya, Tadashi;Meijer, Laurent;Maeda, Masahiro;Yamamoto, Tohru;Masters, Colin L ;Rowe, Christopher C ;Ames, David;Yamamoto, Kazuo;Martins, Ralph N;Gandy, Sam;Suzuki, Toshiharu
Affiliation: Laboratory of Neuroscience, Graduate School of Pharmaceutical Sciences, Hokkaido University, Sapporo, Japan
Department of Integrated Biosciences, Graduate School of Frontier Sciences, University of Tokyo, Kashiwa, Japan
Section of Cell Biology and Pathology, Department of Alzheimer's Disease Research, Center for Development of Advanced Medicine for Dementia, National Center for Geriatrics and Gerontology, Obu, Japan
Tsukuba Primate Research Center, National Institutes of Biomedical Innovation, Health and Nutrition, Tsukuba, Japan
Centre of Excellence for Alzheimer's Disease Research and Care, Sir James McCusker Alzheimer's Disease Research Unit, Edith Cowan University, Joodalup, WA, Australia
School of Medical and Health Sciences, Edith Cowan University, Joondalup, WA, Australia
Co-operative Research Centre for Mental Health, Carlton, Victoria, Australia
Department of Biomedical Sciences, Faculty of Medical and Health Sciences, Macquarie University, Sydney, NSW, Australia
Department of Molecular Genetics, Brain Research Institute, Niigata University, Niigata, Japan
Department of Neurology, Higashi Matsudo Municipal Hospital, Matsudo, Japan
Molecular Neuroscience Research Center, Shiga University of Medical Science, Otsu, Japan
ManRos Therapeutics, Centre de Perharidy, Roscoff, Bretagne, France
Immuno-Biological Laboratories Co., Ltd. (IBL), Fujioka, Japan
Laboratory of Neuroscience, Graduate School of Pharmaceutical Sciences, Hokkaido University, Sapporo, Japan
Department of Molecular Neurobiology, Faculty of Medicine, Kagawa University, Miki-cho, Kagawa, Japan
Neurodegeneration Division, The Florey Institute, The University of Melbourne, Parkville, Victoria, Australia
Department of Nuclear Medicine and Centre for PET, Austin Health, Heidelberg, Victoria, Australia
National Ageing Research Institute, Parkville, Victoria, Australia
Academic Unit for Psychiatry of Old age, St. George's Hospital, The University of Melbourne, Parkville, Victoria, Australia
Department of Integrated Biosciences, Graduate School of Frontier Sciences, University of Tokyo, Kashiwa, Japan
Mount Sinai Center for Cognitive Health and NFL Neurological Care, Icahn School of Medicine at Mount Sinai, New York, NY, USA
Issue Date: 7-Nov-2019
metadata.dc.date: 2019-11-07
Publication information: Alzheimer's & dementia (New York, N. Y.) 2019; 5: 740-750
Abstract: Neuronal p3-Alcβ peptides are generated from the precursor protein Alcadein β (Alcβ) through cleavage by α- and γ-secretases of the amyloid β (Aβ) protein precursor (APP). To reveal whether p3-Alcβ is involved in Alzheimer's disease (AD) contributes for the development of novel therapy and/or drug targets. We developed new sandwich enzyme-linked immunosorbent assay (sELISA) systems to quantitate levels of p3-Alcβ in the cerebrospinal fluid (CSF). In monkeys, CSF p3-Alcβ decreases with age, and the aging is also accompanied by decreased brain expression of Alcβ. In humans, CSF p3-Alcβ levels decrease to a greater extent in those with AD than in age-matched controls. Subjects carrying presenilin gene mutations show a significantly lower CSF p3-Alcβ level. A cell study with an inverse modulator of γ-secretase remarkably reduces the generation of p3-Alcβ37 while increasing the production of Aβ42. Aging decreases the generation of p3-Alcβ, and further significant decrease of p3-Alcβ caused by aberrant γ-secretase activity may accelerate pathogenesis in AD.
URI: http://ahro.austin.org.au/austinjspui/handle/1/22171
DOI: 10.1016/j.trci.2019.09.015
ORCID: 0000-0003-3910-2453
PubMed URL: 31754625
Type: Journal Article
Subjects: Aftin-5
Alcadein
Alzheimer's disease
Amyloid β-peptide
Calsyntenin
Cerebrospinal fluid
p3-Alc
γ-secretase
Appears in Collections:Journal articles

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