Document Type

Journal Article

Publication Title

Alzheimer's and Dementia: Translational Research and Clinical Interventions

Publisher

Elsevier

School

Centre of Excellence for Alzheimer’s Disease Research and Care / School of Medical and Health Sciences

RAS ID

30151

Funders

Funding information available at: https://doi.org/10.1016/j.trci.2019.09.015

Comments

Hata, S., Omori, C., Kimura, A., Saito, H., Kimura, N., Gupta, V., ... Suzuki, T., (2019). 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. Alzheimer's and Dementia: Translational Research and Clinical Interventions, 5, 740-750. Available here

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.

DOI

10.1016/j.trci.2019.09.015

Creative Commons License

Creative Commons Attribution-Noncommercial-No Derivative Works 4.0 License
This work is licensed under a Creative Commons Attribution-Noncommercial-No Derivative Works 4.0 License.

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