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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 | 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: | https://ahro.austin.org.au/austinjspui/handle/1/22171 | DOI: | 10.1016/j.trci.2019.09.015 | ORCID: | 0000-0003-3910-2453 | Journal: | Alzheimer's & dementia (New York, N. Y.) | PubMed URL: | 31754625 | Type: | Journal Article | Subjects: | Aftin-5 Alcadein Alzheimer's disease Amyloid β-peptide Calsyntenin Cerebrospinal fluid p3-Alc γ-secretase |
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