Decrease in p3-Alcb37 and p3-Alcb40, products of Alcadein b generated by g-secretase cleavages, in aged monkeys and patients with Alzheimer’s disease
Veer Gupta, Edith Cowan UniversityFollow
Steve Pedrini, Edith Cowan UniversityFollow
Kevin Taddei, Edith Cowan UniversityFollow
Colin L. Masters
Chris C. Rowe
Ralph N. Martins, Edith Cowan UniversityFollow
ORCID : 0000-0002-8106-7957
Alzheimer's & Dementia: Translational Research & Clinical Interventions
School of Medical and Health Sciences
KAKENHI Japan Society for the Promotion of Science Strategic Research Program for Brain Scinces from the Japan Agency for Medical Research and Development Naito Foundation Grant-in-Aid
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.
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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 & Dementia: Translational Research & Clinical Interventions, 5(1), 740-750. https://doi.org/10.1016/j.trci.2019.09.015