| First Author | Xie J | Year | 2021 |
| Journal | Acta Neuropathol Commun | Volume | 9 |
| Issue | 1 | Pages | 163 |
| PubMed ID | 34620254 | Mgi Jnum | J:311720 |
| Mgi Id | MGI:6771440 | Doi | 10.1186/s40478-021-01253-z |
| Citation | Xie J, et al. (2021) Low-grade peripheral inflammation affects brain pathology in the App(NL-G-F)mouse model of Alzheimer's disease. Acta Neuropathol Commun 9(1):163 |
| abstractText | Alzheimer's disease (AD) is a chronic neurodegenerative disease characterized by the accumulation of amyloid beta (Abeta) and neurofibrillary tangles. The last decade, it became increasingly clear that neuroinflammation plays a key role in both the initiation and progression of AD. Moreover, also the presence of peripheral inflammation has been extensively documented. However, it is still ambiguous whether this observed inflammation is cause or consequence of AD pathogenesis. Recently, this has been studied using amyloid precursor protein (APP) overexpression mouse models of AD. However, the findings might be confounded by APP-overexpression artifacts. Here, we investigated the effect of low-grade peripheral inflammation in the APP knock-in (App(NL-G-F)) mouse model. This revealed that low-grade peripheral inflammation affects (1) microglia characteristics, (2) blood-cerebrospinal fluid barrier integrity, (3) peripheral immune cell infiltration and (4) Abeta deposition in the brain. Next, we identified mechanisms that might cause this effect on AD pathology, more precisely Abeta efflux, persistent microglial activation and insufficient Abeta clearance, neuronal dysfunction and promotion of Abeta aggregation. Our results further strengthen the believe that even low-grade peripheral inflammation has detrimental effects on AD progression and may further reinforce the idea to modulate peripheral inflammation as a therapeutic strategy for AD. |
