Cargando…

COL25A1 triggers and promotes Alzheimer’s disease-like pathology in vivo

Collagen XXV alpha 1 (COL25A1) is a collagenous type II transmembrane protein purified from senile plaques of Alzheimer’s disease (AD) brains. COL25A1 alleles have been associated with increased risk for AD in a Swedish population. COL25A1 is specifically expressed in neurons and binds to aggregated...

Descripción completa

Detalles Bibliográficos
Autores principales: Tong, Ying, Xu, Ying, Scearce-Levie, Kimberly, Ptáček, Louis J., Fu, Ying-Hui
Formato: Texto
Lenguaje:English
Publicado: Springer-Verlag 2009
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2807601/
https://www.ncbi.nlm.nih.gov/pubmed/19548013
http://dx.doi.org/10.1007/s10048-009-0201-5
_version_ 1782176415138971648
author Tong, Ying
Xu, Ying
Scearce-Levie, Kimberly
Ptáček, Louis J.
Fu, Ying-Hui
author_facet Tong, Ying
Xu, Ying
Scearce-Levie, Kimberly
Ptáček, Louis J.
Fu, Ying-Hui
author_sort Tong, Ying
collection PubMed
description Collagen XXV alpha 1 (COL25A1) is a collagenous type II transmembrane protein purified from senile plaques of Alzheimer’s disease (AD) brains. COL25A1 alleles have been associated with increased risk for AD in a Swedish population. COL25A1 is specifically expressed in neurons and binds to aggregated Aβ in vitro. However, its contribution to the pathogenesis of AD and in vivo function are unknown. Here, we report that over-expression of COL25A1 in transgenic mice increases p35/p25 and β-site APP-cleaving enzyme 1 (BACE1) levels, facilitates intracellular aggregation and extracellular matrix deposits of Aβ, and causes synaptophysin loss and astrocyte activation. COL25A1 mice displayed reduced anxiety-like behavior in elevated plus maze and open field tests and significantly slower swimming speed in Morris water maze. In stable cell lines, motifs in noncollagenous domains of COL25A1 were important for the induction of BACE1 expression. These findings demonstrate that COL25A1 leads to AD-like pathology in vivo. Modulation of COL25A1 function may represent an alternative therapeutic intervention for AD. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s10048-009-0201-5) contains supplementary material, which is available to authorized users.
format Text
id pubmed-2807601
institution National Center for Biotechnology Information
language English
publishDate 2009
publisher Springer-Verlag
record_format MEDLINE/PubMed
spelling pubmed-28076012010-01-22 COL25A1 triggers and promotes Alzheimer’s disease-like pathology in vivo Tong, Ying Xu, Ying Scearce-Levie, Kimberly Ptáček, Louis J. Fu, Ying-Hui Neurogenetics Original Article Collagen XXV alpha 1 (COL25A1) is a collagenous type II transmembrane protein purified from senile plaques of Alzheimer’s disease (AD) brains. COL25A1 alleles have been associated with increased risk for AD in a Swedish population. COL25A1 is specifically expressed in neurons and binds to aggregated Aβ in vitro. However, its contribution to the pathogenesis of AD and in vivo function are unknown. Here, we report that over-expression of COL25A1 in transgenic mice increases p35/p25 and β-site APP-cleaving enzyme 1 (BACE1) levels, facilitates intracellular aggregation and extracellular matrix deposits of Aβ, and causes synaptophysin loss and astrocyte activation. COL25A1 mice displayed reduced anxiety-like behavior in elevated plus maze and open field tests and significantly slower swimming speed in Morris water maze. In stable cell lines, motifs in noncollagenous domains of COL25A1 were important for the induction of BACE1 expression. These findings demonstrate that COL25A1 leads to AD-like pathology in vivo. Modulation of COL25A1 function may represent an alternative therapeutic intervention for AD. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s10048-009-0201-5) contains supplementary material, which is available to authorized users. Springer-Verlag 2009-06-23 2010 /pmc/articles/PMC2807601/ /pubmed/19548013 http://dx.doi.org/10.1007/s10048-009-0201-5 Text en © The Author(s) 2009 https://creativecommons.org/licenses/by-nc/4.0/ This article is distributed under the terms of the Creative Commons Attribution Noncommercial License which permits any noncommercial use, distribution, and reproduction in any medium, provided the original author(s) and source are credited.
spellingShingle Original Article
Tong, Ying
Xu, Ying
Scearce-Levie, Kimberly
Ptáček, Louis J.
Fu, Ying-Hui
COL25A1 triggers and promotes Alzheimer’s disease-like pathology in vivo
title COL25A1 triggers and promotes Alzheimer’s disease-like pathology in vivo
title_full COL25A1 triggers and promotes Alzheimer’s disease-like pathology in vivo
title_fullStr COL25A1 triggers and promotes Alzheimer’s disease-like pathology in vivo
title_full_unstemmed COL25A1 triggers and promotes Alzheimer’s disease-like pathology in vivo
title_short COL25A1 triggers and promotes Alzheimer’s disease-like pathology in vivo
title_sort col25a1 triggers and promotes alzheimer’s disease-like pathology in vivo
topic Original Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2807601/
https://www.ncbi.nlm.nih.gov/pubmed/19548013
http://dx.doi.org/10.1007/s10048-009-0201-5
work_keys_str_mv AT tongying col25a1triggersandpromotesalzheimersdiseaselikepathologyinvivo
AT xuying col25a1triggersandpromotesalzheimersdiseaselikepathologyinvivo
AT scearceleviekimberly col25a1triggersandpromotesalzheimersdiseaselikepathologyinvivo
AT ptaceklouisj col25a1triggersandpromotesalzheimersdiseaselikepathologyinvivo
AT fuyinghui col25a1triggersandpromotesalzheimersdiseaselikepathologyinvivo