PT  - JOURNAL ARTICLE
AU  - Karen N McFarland
AU  - Carolina Ceballos
AU  - Awilda Rosario
AU  - Thomas Ladd
AU  - Brenda Moore
AU  - Griffin Golde
AU  - Xue Wang
AU  - Mariet Allen
AU  - Nilüfer Ertekin-Taner
AU  - Cory C Funk
AU  - Max Robinson
AU  - Priyanka Baloni
AU  - Noa Rappaport
AU  - Paramita Chakrabarty
AU  - Todd E Golde
TI  - Microglia show differential transcriptomic response to Aβ peptide aggregates ex vivo and in vivo
AID  - 10.26508/lsa.202101108
DP  - 2021 Jul 01
TA  - Life Science Alliance
PG  - e202101108
VI  - 4
IP  - 7
4099  - https://www.life-science-alliance.org/content/4/7/e202101108.short
4100  - https://www.life-science-alliance.org/content/4/7/e202101108.full
SO  - Life Sci. Alliance2021 Jul 01; 4
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.