| First Author | Lloyd GM | Year | 2021 |
| Journal | Mol Neurodegener | Volume | 16 |
| Issue | 1 | Pages | 63 |
| PubMed ID | 34503546 | Mgi Jnum | J:311309 |
| Mgi Id | MGI:6766289 | Doi | 10.1186/s13024-021-00486-9 |
| Citation | Lloyd GM, et al. (2021) Collusion of alpha-Synuclein and Abeta aggravating co-morbidities in a novel prion-type mouse model. Mol Neurodegener 16(1):63 |
| abstractText | BACKGROUND: The misfolding of host-encoded proteins into pathological prion conformations is a defining characteristic of many neurodegenerative disorders, including Alzheimer's disease, Parkinson's disease, and Lewy body dementia. A current area of intense study is the way in which the pathological deposition of these proteins might influence each other, as various combinations of co-pathology between prion-capable proteins are associated with exacerbation of disease. A spectrum of pathological, genetic and biochemical evidence provides credence to the notion that amyloid beta (Abeta) accumulation can induce and promote alpha-synuclein pathology, driving neurodegeneration. METHODS: To assess the interplay between alpha-synuclein and Abeta on protein aggregation kinetics, we crossed mice expressing human alpha-synuclein (M20) with APPswe/PS1dE9 transgenic mice (L85) to generate M20/L85 mice. We then injected alpha-synuclein preformed fibrils (PFFs) unilaterally into the hippocampus of 6-month-old mice, harvesting 2 or 4 months later. RESULTS: Immunohistochemical analysis of M20/L85 mice revealed that pre-existing Abeta plaques exacerbate the spread and deposition of induced alpha-synuclein pathology. This process was associated with increased neuroinflammation. Unexpectedly, the injection of alpha-synuclein PFFs in L85 mice enhanced the deposition of Abeta; whereas the level of Abeta deposition in M20/L85 bigenic mice, injected with alpha-synuclein PFFs, did not differ from that of mice injected with PBS. CONCLUSIONS: These studies reveal novel and unexpected interplays between alpha-synuclein pathology, Abeta and neuroinflammation in mice that recapitulate the pathology of Alzheimer's disease and Lewy body dementia. |
