| First Author | Kozyrev N | Year | 2020 |
| Journal | J Neuropathol Exp Neurol | Volume | 79 |
| Issue | 11 | Pages | 1147-1162 |
| PubMed ID | 33011810 | Mgi Jnum | J:352669 |
| Mgi Id | MGI:7704311 | Doi | 10.1093/jnen/nlaa093 |
| Citation | Kozyrev N, et al. (2020) Infiltrating Hematogenous Macrophages Aggregate Around beta-Amyloid Plaques in an Age- and Sex-Dependent Manner in a Mouse Model of Alzheimer Disease. J Neuropathol Exp Neurol 79(11):1147-1162 |
| abstractText | beta-Amyloid (Abeta) plaques can trigger chronic inflammation in the cellular environment that recruits infiltrating macrophages during the course of Alzheimer disease (AD). Activated macrophages release pro-inflammatory cytokines that increase neurotoxicity associated with AD. A major impediment to investigating neuroinflammation involving macrophage activity is the inability to discriminate resident microglial macrophages (mMvarphi) from hematogenous macrophages (hMvarphi), as they are morphologically and phenotypically similar when activated. To distinguish between mMvarphi and hMvarphi and to determine their respective roles in chronic inflammation associated with the progression of amyloidosis, we used lys-EGFP-ki transgenic mice that express enhanced green fluorescent protein in hMvarphi, but not in mMvarphi. These mice were crossed with 5XFAD mice. The offspring demonstrated robust AD pathology and enabled visual discrimination of mMvarphi from hMvarphi. Mutant mice demonstrated robust increases in Abeta1-42, area of Abeta plaques, gliosis and deficits in spatial learning by age 5 months. The time-course of Abeta accumulation, paralleled by the accumulation of hMvarphi around Abeta plaques, was more robust in female compared with male mice and preceded behavioral changes. Thus, the accumulation of infiltrating hMvarphi around Abeta plaques was age- and sex-dependent and preceded cognitive impairment. |
