TY - JOUR
T1 - Infusion of blood from mice displaying cerebral amyloidosis accelerates amyloid pathology in animal models of Alzheimer’s disease
AU - Morales, Rodrigo
AU - Duran-Aniotz, Claudia
AU - Bravo-Alegria, Javiera
AU - Estrada, Lisbell D.
AU - Shahnawaz, Mohammad
AU - Hu, Ping Ping
AU - Kramm, Carlos
AU - Morales-Scheihing, Diego
AU - Urayama, Akihiko
AU - Soto, Claudio
N1 - Funding Information:
This work was supported by a grant from the Mitchell Foundation (to CS), NIH grant RF1AG059321 (to CS and RM), grants from the Alzheimer’s Association (MNIRGD-12-243075 to RM and AARG-591107 to CDA), grants from FONDECYT (3140065 to CDA and 3110052 to LDE) and FONDEF (ID20I10152 to CDA).
Funding Information:
The authors would like to thank Dr. Robia Pautler (Baylor College of Medicine) for providing some old Tg2576 mice to complete our experiments, and Ms. Taneasha Washington and Dr. Christine Beeton for technical assistance. We would also like to acknowledge Dr. Ines Moreno-Gonzalez, Mrs. Andrea Flores and Dr. Elizabeth Sanchez-Mejias for valuable technical assistance.
Publisher Copyright:
© 2020, The Author(s).
PY - 2020/12
Y1 - 2020/12
N2 - 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.
AB - 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.
KW - Amyloid-beta
KW - Blood transfusion
KW - Prions
UR - http://www.scopus.com/inward/record.url?scp=85097254459&partnerID=8YFLogxK
U2 - 10.1186/s40478-020-01087-1
DO - 10.1186/s40478-020-01087-1
M3 - Article
C2 - 33287898
AN - SCOPUS:85097254459
SN - 2051-5960
VL - 8
JO - Acta Neuropathologica Communications
JF - Acta Neuropathologica Communications
IS - 1
M1 - 213
ER -