| First Author | Prokop S | Year | 2015 |
| Journal | J Exp Med | Volume | 212 |
| Issue | 11 | Pages | 1811-8 |
| PubMed ID | 26458768 | Mgi Jnum | J:229027 |
| Mgi Id | MGI:5750251 | Doi | 10.1084/jem.20150479 |
| Citation | Prokop S, et al. (2015) Impact of peripheral myeloid cells on amyloid-beta pathology in Alzheimer's disease-like mice. J Exp Med 212(11):1811-8 |
| abstractText | Although central nervous system-resident microglia are believed to be ineffective at phagocytosing and clearing amyloid-beta (Abeta), a major pathological hallmark of Alzheimer's disease (AD), it has been suggested that peripheral myeloid cells constitute a heterogeneous cell population with greater Abeta-clearing capabilities. Here, we demonstrate that the conditional ablation of resident microglia in CD11b-HSVTK (TK) mice is followed by a rapid repopulation of the brain by peripherally derived myeloid cells. We used this system to directly assess the ability of peripheral macrophages to reduce Abeta plaque pathology and therefore depleted and replaced the pool of resident microglia with peripherally derived myeloid cells in Abeta-carrying APPPS1 mice crossed to TK mice (APPPS1;TK). Despite a nearly complete exchange of resident microglia with peripheral myeloid cells, there was no significant change in Abeta burden or APP processing in APPPS1;TK mice. Importantly, however, newly recruited peripheral myeloid cells failed to cluster around Abeta deposits. Even additional anti-Abeta antibody treatment aimed at engaging myeloid cells with amyloid plaques neither directed peripherally derived myeloid cells to amyloid plaques nor altered Abeta burden. These data demonstrate that mere recruitment of peripheral myeloid cells to the brain is insufficient in substantially clearing Abeta burden and suggest that specific additional triggers appear to be required to exploit the full potential of myeloid cell-based therapies for AD. |
