Microglia show differential transcriptomic response to Aβ peptide aggregates ex vivo and in vivo.
IF: 5.781
Cited by: 11


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.


Spatial Transcriptomics
Gene Expression

MeSH terms

Alzheimer Disease
Amyloid beta-Peptides
Amyloid beta-Protein Precursor
Disease Models, Animal
Gene Expression
Mice, Inbred C3H
Mice, Inbred C57BL
Mice, Transgenic
Neurofibrillary Tangles
Primary Cell Culture


McFarland, Karen N
Ceballos, Carolina
Rosario, Awilda
Ladd, Thomas
Moore, Brenda
Golde, Griffin
Wang, Xue
Allen, Mariet
Ertekin-Taner, Nilüfer
Funk, Cory C
Robinson, Max
Baloni, Priyanka
Rappaport, Noa
Chakrabarty, Paramita
Golde, Todd E

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