RT Journal Article
SR Electronic
T1 Microglia show differential transcriptomic response to Aβ peptide aggregates ex vivo and in vivo
JF Life Science Alliance
JO Life Sci. Alliance
FD Life Science Alliance LLC
SP e202101108
DO 10.26508/lsa.202101108
VO 4
IS 7
A1 Karen N McFarland
A1 Carolina Ceballos
A1 Awilda Rosario
A1 Thomas Ladd
A1 Brenda Moore
A1 Griffin Golde
A1 Xue Wang
A1 Mariet Allen
A1 Nilüfer Ertekin-Taner
A1 Cory C Funk
A1 Max Robinson
A1 Priyanka Baloni
A1 Noa Rappaport
A1 Paramita Chakrabarty
A1 Todd E Golde
YR 2021
UL https://www.life-science-alliance.org/content/4/7/e202101108.abstract
AB Aggregation and accumulation of amyloid-β (Aβ) is a defining feature of Alzheimer’s disease pathology. To study microglial responses to Aβ, we applied exogenous Aβ peptide, in either oligomeric or fibrillar conformation, to primary mouse microglial cultures and evaluated system-level transcriptional changes and then compared these with transcriptomic changes in the brains of CRND8 APP mice. We find that primary microglial cultures have rapid and massive transcriptional change in response to Aβ. Transcriptomic responses to oligomeric or fibrillar Aβ in primary microglia, although partially overlapping, are distinct and are not recapitulated in vivo where Aβ progressively accumulates. Furthermore, although classic immune mediators show massive transcriptional changes in the primary microglial cultures, these changes are not observed in the mouse model. Together, these data extend previous studies which demonstrate that microglia responses ex vivo are poor proxies for in vivo responses. Finally, these data demonstrate the potential utility of using microglia as biosensors of different aggregate conformation, as the transcriptional responses to oligomeric and fibrillar Aβ can be distinguished.