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.
Aftin-5
Alcadein
Alzheimer's disease
Amyloid β-peptide
Calsyntenin
Cerebrospinal fluid
p3-Alc
γ-secretase
Journal
Alzheimer's & dementia (New York, N. Y.)
ISSN: 2352-8737
Titre abrégé: Alzheimers Dement (N Y)
Pays: United States
ID NLM: 101650118
Informations de publication
Date de publication:
2019
2019
Historique:
entrez:
23
11
2019
pubmed:
23
11
2019
medline:
23
11
2019
Statut:
epublish
Résumé
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. We developed new sandwich enzyme-linked immunosorbent assay (sELISA) systems to quantitate levels of p3-Alcβ in the cerebrospinal fluid (CSF). 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. 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.
Identifiants
pubmed: 31754625
doi: 10.1016/j.trci.2019.09.015
pii: S2352-8737(19)30076-9
pmc: PMC6854065
doi:
Types de publication
Journal Article
Langues
eng
Pagination
740-750Informations de copyright
© 2019 The Authors.
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