| First Author | Varvel NH | Year | 2015 |
| Journal | J Exp Med | Volume | 212 |
| Issue | 11 | Pages | 1803-9 |
| PubMed ID | 26458770 | Mgi Jnum | J:229025 |
| Mgi Id | MGI:5750249 | Doi | 10.1084/jem.20150478 |
| Citation | Varvel NH, et al. (2015) Replacement of brain-resident myeloid cells does not alter cerebral amyloid-beta deposition in mouse models of Alzheimer's disease. J Exp Med 212(11):1803-9 |
| abstractText | Immune cells of myeloid lineage are encountered in the Alzheimer's disease (AD) brain, where they cluster around amyloid-beta plaques. However, assigning functional roles to myeloid cell subtypes has been problematic, and the potential for peripheral myeloid cells to alleviate AD pathology remains unclear. Therefore, we asked whether replacement of brain-resident myeloid cells with peripheral monocytes alters amyloid deposition in two mouse models of cerebral beta-amyloidosis (APP23 and APPPS1). Interestingly, early after repopulation, infiltrating monocytes neither clustered around plaques nor showed Trem2 expression. However, with increasing time in the brain, infiltrating monocytes became plaque associated and also Trem2 positive. Strikingly, however, monocyte repopulation for up to 6 mo did not modify amyloid load in either model, independent of the stage of pathology at the time of repopulation. Our results argue against a long-term role of peripheral monocytes that is sufficiently distinct from microglial function to modify cerebral beta-amyloidosis. Therefore, myeloid replacement by itself is not likely to be effective as a therapeutic approach for AD. |
