Dataset Information

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.

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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Project description:Most of the analytical studies focused on microplastics (MPs) are based on the detection and identification of the polymers constituting the particles. On the other hand, plastic debris in the environment undergoes chemical and physical degradation processes leading not only to mechanical but also to molecular fragmentation quickly resulting in the formation of leachable, soluble and/or volatile degradation products that are released in the environment. We performed the analysis of reference MPs-polymer micropowders obtained by grinding a set of five polymer types down to final size in the 857-509 μm range, namely high- and low-density polyethylene, polystyrene (PS), polypropylene (PP), and polyethylene terephthalate (PET). The reference MPs were artificially aged in a solar-box to investigate their degradation processes by characterizing the aged (photo-oxidized) MPs and their low molecular weight and/or highly oxidized fraction. For this purpose, the artificially aged MPs were subjected to extraction in polar organic solvents, targeting selective recovery of the low molecular weight fractions generated during the artificial aging. Analysis of the extractable fractions and of the residues was carried out by a multi-technique approach combining evolved gas analysis-mass spectrometry (EGA-MS), pyrolysis-gas chromatography-mass spectrometry (Py-GC-MS), and size exclusion chromatography (SEC). The results provided information on the degradation products formed during accelerated aging. Up to 18 wt% of extractable, low molecular weight fraction was recovered from the photo-aged MPs, depending on the polymer type. The photo-degradation products of polyolefins (PE and PP) included a wide range of long chain alcohols, aldehydes, ketones, carboxylic acids, and hydroxy acids, as detected in the soluble fractions of aged samples. SEC analyses also showed a marked decrease in the average molecular weight of PP polymer chains, whereas cross-linking was observed in the case of PS. The most abundant low molecular weight photo-degradation products of PS were benzoic acid and 1,4-benzenedicarboxylic acid, while PET had the highest stability towards aging, as indicated by the modest generation of low molecular weight species.

Dataset Information

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.

Introduction

Methods

Results

Discussion

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.

Similar Datasets

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