Cargando…

Infusion of blood from mice displaying cerebral amyloidosis accelerates amyloid pathology in animal models of Alzheimer’s disease

Previous studies showed that injection of tissue extracts containing amyloid-β (Aβ) aggregates accelerate amyloid deposition in the brain of mouse models of Alzheimer’s disease (AD) through prion-like mechanisms. In this study, we evaluated whether brain amyloidosis could be accelerated by blood inf...

Descripción completa

Detalles Bibliográficos
Autores principales: Morales, Rodrigo, Duran-Aniotz, Claudia, Bravo-Alegria, Javiera, Estrada, Lisbell D., Shahnawaz, Mohammad, Hu, Ping-Ping, Kramm, Carlos, Morales-Scheihing, Diego, Urayama, Akihiko, Soto, Claudio
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7720397/
https://www.ncbi.nlm.nih.gov/pubmed/33287898
http://dx.doi.org/10.1186/s40478-020-01087-1
_version_ 1783619843603300352
author Morales, Rodrigo
Duran-Aniotz, Claudia
Bravo-Alegria, Javiera
Estrada, Lisbell D.
Shahnawaz, Mohammad
Hu, Ping-Ping
Kramm, Carlos
Morales-Scheihing, Diego
Urayama, Akihiko
Soto, Claudio
author_facet Morales, Rodrigo
Duran-Aniotz, Claudia
Bravo-Alegria, Javiera
Estrada, Lisbell D.
Shahnawaz, Mohammad
Hu, Ping-Ping
Kramm, Carlos
Morales-Scheihing, Diego
Urayama, Akihiko
Soto, Claudio
author_sort Morales, Rodrigo
collection PubMed
description Previous studies showed that injection of tissue extracts containing amyloid-β (Aβ) aggregates accelerate amyloid deposition in the brain of mouse models of Alzheimer’s disease (AD) through prion-like mechanisms. In this study, we evaluated whether brain amyloidosis could be accelerated by blood infusions, procedures that have been shown to transmit prion diseases in animals and humans. Young transgenic mice infused with whole blood or plasma from old animals with extensive Aβ deposition in their brains developed significantly higher levels brain amyloidosis and neuroinflammation compared to untreated animals or mice infused with wild type blood. Similarly, intra-venous injection of purified Aβ aggregates accelerated amyloid pathology, supporting the concept that Aβ seeds present in blood can reach the brain to promote neuropathological alterations in the brain of treated animals. However, an amyloid-enhancing effect of other factors present in the blood of donors cannot be discarded. Our results may help to understand the role of peripheral (amyloid-dependent or -independent) factors implicated in the development of AD and uncover new strategies for disease intervention. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s40478-020-01087-1) contains supplementary material, which is available to authorized users.
format Online
Article
Text
id pubmed-7720397
institution National Center for Biotechnology Information
language English
publishDate 2020
publisher BioMed Central
record_format MEDLINE/PubMed
spelling pubmed-77203972020-12-07 Infusion of blood from mice displaying cerebral amyloidosis accelerates amyloid pathology in animal models of Alzheimer’s disease Morales, Rodrigo Duran-Aniotz, Claudia Bravo-Alegria, Javiera Estrada, Lisbell D. Shahnawaz, Mohammad Hu, Ping-Ping Kramm, Carlos Morales-Scheihing, Diego Urayama, Akihiko Soto, Claudio Acta Neuropathol Commun Research Previous studies showed that injection of tissue extracts containing amyloid-β (Aβ) aggregates accelerate amyloid deposition in the brain of mouse models of Alzheimer’s disease (AD) through prion-like mechanisms. In this study, we evaluated whether brain amyloidosis could be accelerated by blood infusions, procedures that have been shown to transmit prion diseases in animals and humans. Young transgenic mice infused with whole blood or plasma from old animals with extensive Aβ deposition in their brains developed significantly higher levels brain amyloidosis and neuroinflammation compared to untreated animals or mice infused with wild type blood. Similarly, intra-venous injection of purified Aβ aggregates accelerated amyloid pathology, supporting the concept that Aβ seeds present in blood can reach the brain to promote neuropathological alterations in the brain of treated animals. However, an amyloid-enhancing effect of other factors present in the blood of donors cannot be discarded. Our results may help to understand the role of peripheral (amyloid-dependent or -independent) factors implicated in the development of AD and uncover new strategies for disease intervention. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s40478-020-01087-1) contains supplementary material, which is available to authorized users. BioMed Central 2020-12-07 /pmc/articles/PMC7720397/ /pubmed/33287898 http://dx.doi.org/10.1186/s40478-020-01087-1 Text en © The Author(s) 2020 Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
spellingShingle Research
Morales, Rodrigo
Duran-Aniotz, Claudia
Bravo-Alegria, Javiera
Estrada, Lisbell D.
Shahnawaz, Mohammad
Hu, Ping-Ping
Kramm, Carlos
Morales-Scheihing, Diego
Urayama, Akihiko
Soto, Claudio
Infusion of blood from mice displaying cerebral amyloidosis accelerates amyloid pathology in animal models of Alzheimer’s disease
title Infusion of blood from mice displaying cerebral amyloidosis accelerates amyloid pathology in animal models of Alzheimer’s disease
title_full Infusion of blood from mice displaying cerebral amyloidosis accelerates amyloid pathology in animal models of Alzheimer’s disease
title_fullStr Infusion of blood from mice displaying cerebral amyloidosis accelerates amyloid pathology in animal models of Alzheimer’s disease
title_full_unstemmed Infusion of blood from mice displaying cerebral amyloidosis accelerates amyloid pathology in animal models of Alzheimer’s disease
title_short Infusion of blood from mice displaying cerebral amyloidosis accelerates amyloid pathology in animal models of Alzheimer’s disease
title_sort infusion of blood from mice displaying cerebral amyloidosis accelerates amyloid pathology in animal models of alzheimer’s disease
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7720397/
https://www.ncbi.nlm.nih.gov/pubmed/33287898
http://dx.doi.org/10.1186/s40478-020-01087-1
work_keys_str_mv AT moralesrodrigo infusionofbloodfrommicedisplayingcerebralamyloidosisacceleratesamyloidpathologyinanimalmodelsofalzheimersdisease
AT durananiotzclaudia infusionofbloodfrommicedisplayingcerebralamyloidosisacceleratesamyloidpathologyinanimalmodelsofalzheimersdisease
AT bravoalegriajaviera infusionofbloodfrommicedisplayingcerebralamyloidosisacceleratesamyloidpathologyinanimalmodelsofalzheimersdisease
AT estradalisbelld infusionofbloodfrommicedisplayingcerebralamyloidosisacceleratesamyloidpathologyinanimalmodelsofalzheimersdisease
AT shahnawazmohammad infusionofbloodfrommicedisplayingcerebralamyloidosisacceleratesamyloidpathologyinanimalmodelsofalzheimersdisease
AT hupingping infusionofbloodfrommicedisplayingcerebralamyloidosisacceleratesamyloidpathologyinanimalmodelsofalzheimersdisease
AT krammcarlos infusionofbloodfrommicedisplayingcerebralamyloidosisacceleratesamyloidpathologyinanimalmodelsofalzheimersdisease
AT moralesscheihingdiego infusionofbloodfrommicedisplayingcerebralamyloidosisacceleratesamyloidpathologyinanimalmodelsofalzheimersdisease
AT urayamaakihiko infusionofbloodfrommicedisplayingcerebralamyloidosisacceleratesamyloidpathologyinanimalmodelsofalzheimersdisease
AT sotoclaudio infusionofbloodfrommicedisplayingcerebralamyloidosisacceleratesamyloidpathologyinanimalmodelsofalzheimersdisease