Veer Gupta, Edith Cowan UniversityFollow
Steve Pedrini, Edith Cowan UniversityFollow
Eugene Hone, Edith Cowan UniversityFollow
Kevin Taddei, Edith Cowan UniversityFollow
Colin L. Masters
Chris C. Rowe
Ralph N. Martins, Edith Cowan UniversityFollow
Alzheimer's and Dementia: Translational Research and Clinical Interventions
Centre of Excellence for Alzheimer’s Disease Research and Care / School of Medical and Health Sciences
Funding information available at: https://doi.org/10.1016/j.trci.2019.09.015
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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