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| Status |
Public on Oct 24, 2021 |
| Title |
Blood-borne macrophages contribute to Alzheimer's disease modification through a TREM2-independent pathway |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
Microglia and monocyte-derived macrophages (MDM) are key players in coping with Alzheimer's disease (AD). In amyloidosis mouse models, activation of microglia was found to be TREM2-dependent. Here, using Trem2-/-5xFAD mice, we assessed whether MDM act via a TREM2-dependent pathway. We adopted a treatment protocol targeting the programmed cell death ligand-1 (PD-L1) immune checkpoint, previously shown to modify AD via MDM involvement. Blocking PD-L1 in Trem2-/-5xFAD mice resulted in cognitive improvement and reduced levels of water-soluble amyloid beta (Aβ)1-42 with no effect on amyloid plaque burden. Single-cell RNA sequencing revealed that MDM, derived from both Trem2-/- and Trem2+/+5xFAD mouse brains, express a unique set of genes encoding scavenger receptors (e.g. Mrc1, Msr1). Blocking monocytes trafficking using anti-CCR2 antibody completely abrogated the cognitive improvement induced by anti-PD-L1 in Trem2-/-5xFAD mice, and similarly but to lower extent in Trem2+/+5xFAD mice. These results highlight a TREM2-independent disease-modifying activity of MDM in amyloidosis mouse model.
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| Overall design |
Indicated cell types were isolated from the brains of TREM2+/+ or TREM2-/- 5xFAD mice. Cells were sorted and single-cell libraries of cell transcripts were sequenced.
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| Contributor(s) |
Dvir-Szternfeld R, Castellani G, Arad M, Cahalon L, Colaiuta SP, Keren-Shaul H, Croese T, Burgaletto C, Baruch K, Ulland T, Colonna M, Weiner A, Amit I, Schwartz M |
| Citation missing |
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| Submission date |
Jun 03, 2021 |
| Last update date |
Oct 26, 2021 |
| Contact name |
Ido Amit |
| E-mail(s) |
ido.amit@weizmann.ac.il
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| Phone |
972-8-9343338
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| Organization name |
Weizmann Institute of Science
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| Department |
Immunology
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| Street address |
234 Herzl st.
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| City |
Rehovot |
| ZIP/Postal code |
760001 |
| Country |
Israel |
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| Platforms (1) |
| GPL24247 |
Illumina NovaSeq 6000 (Mus musculus) |
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| Samples (63)
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| Relations |
| BioProject |
PRJNA734862 |
| SRA |
SRP322431 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE176085_M_metadata_s.txt.gz |
401.9 Kb |
(ftp)(http) |
TXT |
| GSE176085_RAW.tar |
37.3 Mb |
(http)(custom) |
TAR (of TXT) |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data provided as supplementary file |
| Processed data are available on Series record |
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