Dataset Information

Decrease in p3-Alc?37 and p3-Alc?40, products of Alcadein ? generated by ?-secretase cleavages, in aged monkeys and patients with Alzheimer's disease.

ABSTRACT:

Introduction

Neuronal p3-Alc? peptides are generated from the precursor protein Alcadein ? (Alc?) through cleavage by ?- and ?-secretases of the amyloid ? (A?) protein precursor (APP). To reveal whether p3-Alc? 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-Alc? in the cerebrospinal fluid (CSF).

Results

In monkeys, CSF p3-Alc? decreases with age, and the aging is also accompanied by decreased brain expression of Alc?. In humans, CSF p3-Alc? 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-Alc? level. A cell study with an inverse modulator of ?-secretase remarkably reduces the generation of p3-Alc?37 while increasing the production of A?42.

Discussion

Aging decreases the generation of p3-Alc?, and further significant decrease of p3-Alc? caused by aberrant ?-secretase activity may accelerate pathogenesis in AD.

SUBMITTER: Hata S

PROVIDER: S-EPMC6854065 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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Publications

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.

Hata Saori S Omori Chiori C Kimura Ayano A Saito Haruka H Kimura Nobuyuki N Gupta Veer V Pedrini Steve S Hone Eugene E Chatterjee Pratishtha P Taddei Kevin K Kasuga Kensaku K Ikeuchi Takeshi T Waragai Masaaki M Nishimura Masaki M Hu Anqi A Nakaya Tadashi T Meijer Laurent L Maeda Masahiro M Yamamoto Tohru T Masters Colin L CL Rowe Chris C CC Ames David D Yamamoto Kazuo K Martins Ralph N RN Gandy Sam S Suzuki Toshiharu T

Alzheimer's & dementia (New York, N. Y.) 20191107

<h4>Introduction</h4>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.<h4>Methods</h4>We developed new sandwich enzyme-linked immunosorbent assay (sELISA) systems to quantitate levels of p3-Alcβ in the cerebrospinal fluid (CSF).<h4>Results</h ...[more]

PMID: 31754625

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