@article{249f7f11f1ac414fa06845517b0cfe1a,
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",
abstract = "Introduction: 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. Methods: We developed new sandwich enzyme-linked immunosorbent assay (sELISA) systems to quantitate levels of p3-Alcβ in the cerebrospinal fluid (CSF). Results: 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. Discussion: 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.",
keywords = "Aftin-5, Alcadein, Alzheimer's disease, Amyloid β-peptide, Calsyntenin, Cerebrospinal fluid, p3-Alc, γ-secretase",
author = "Saori Hata and Chiori Omori and Ayano Kimura and Haruka Saito and Nobuyuki Kimura and Veer Gupta and Steve Pedrini and Eugene Hone and Pratishtha Chatterjee and Kevin Taddei and Kensaku Kasuga and Takeshi Ikeuchi and Masaaki Waragai and Masaki Nishimura and Anqi Hu and Tadashi Nakaya and Laurent Meijer and Masahiro Maeda and Tohru Yamamoto and Masters, {Colin L.} and Rowe, {Chris C.} and David Ames and Kazuo Yamamoto and Martins, {Ralph N.} and Sam Gandy and Toshiharu Suzuki",
note = "Funding Information: The authors wish to dedicate this article to the late Professor Paul Greengard (Molecular and Cellular Neuroscience in the Rockefeller University) who died on April 13, 2019, and was one of the leading scientists in molecular and cellular research in the Alzheimer's field, and many of coauthors in this article worked in Paul's Laboratory and/or productively collaborated with Paul. We thank all the laboratory members who contributed important in helpful suggestions and discussion. This work was supported in part by KAKENHI , a Grants-in-Aid for Scientific Research 18K07384 to SH, 262930110 and 18H02566 to TS from Japan Society for the Promotion of Science (JSPS) in Japan, by the Strategic Research Program for Brain Sciences from the Japan Agency for Medical Research and Development ( JP19dm0107142h0004 for TS, JP19dm0107141h0004 for MN, and JP19dm0107143h0004 for TI ) in Japan, The Naito Foundation (to SH) in Japan, and by a Grant-in-Aid for JSPS Research Fellow 17J06504 to CO in Japan. Funding Information: The authors wish to dedicate this article to the late Professor Paul Greengard (Molecular and Cellular Neuroscience in the Rockefeller University) who died on April 13, 2019, and was one of the leading scientists in molecular and cellular research in the Alzheimer's field, and many of coauthors in this article worked in Paul's Laboratory and/or productively collaborated with Paul. We thank all the laboratory members who contributed important in helpful suggestions and discussion. This work was supported in part by KAKENHI, a Grants-in-Aid for Scientific Research 18K07384 to SH, 262930110 and 18H02566 to TS from Japan Society for the Promotion of Science (JSPS) in Japan, by the Strategic Research Program for Brain Sciences from the Japan Agency for Medical Research and Development (JP19dm0107142h0004 for TS, JP19dm0107141h0004 for MN, and JP19dm0107143h0004 for TI) in Japan, The Naito Foundation (to SH) in Japan, and by a Grant-in-Aid for JSPS Research Fellow 17J06504 to CO in Japan. Publisher Copyright: {\textcopyright} 2019 The Authors",
year = "2019",
doi = "10.1016/j.trci.2019.09.015",
language = "English",
volume = "5",
pages = "740--750",
journal = "Alzheimer's and Dementia: Translational Research and Clinical Interventions",
issn = "2352-8737",
publisher = "John Wiley & Sons Inc.",
}