| First Author | Bassil F | Year | 2020 |
| Journal | Neuron | Volume | 105 |
| Issue | 2 | Pages | 260-275.e6 |
| PubMed ID | 31759806 | Mgi Jnum | J:283375 |
| Mgi Id | MGI:6386510 | Doi | 10.1016/j.neuron.2019.10.010 |
| Citation | Bassil F, et al. (2020) Amyloid-Beta (Abeta) Plaques Promote Seeding and Spreading of Alpha-Synuclein and Tau in a Mouse Model of Lewy Body Disorders with Abeta Pathology. Neuron 105(2):260-275.e6 |
| abstractText | Studies have shown an overlap of Abeta plaques, tau tangles, and alpha-synuclein (alpha-syn) pathologies in the brains of Alzheimer's disease (AD) and Parkinson's disease (PD) with dementia (PDD) patients, with increased pathological burden correlating with severity of cognitive and motor symptoms. Despite the observed co-pathology and concomitance of motor and cognitive phenotypes, the consequences of the primary amyloidogenic protein on the secondary pathologies remain poorly understood. To better define the relationship between alpha-syn and Abeta plaques, we injected alpha-syn preformed fibrils (alpha-syn mpffs) into mice with abundant Abeta plaques. Abeta deposits dramatically accelerated alpha-syn pathogenesis and spread throughout the brain. Remarkably, hyperphosphorylated tau (p-tau) was induced in alpha-syn mpff-injected 5xFAD mice. Finally, alpha-syn mpff-injected 5xFAD mice showed neuron loss that correlated with the progressive decline of cognitive and motor performance. Our findings suggest a "feed-forward" mechanism whereby Abeta plaques enhance endogenous alpha-syn seeding and spreading over time post-injection with mpffs. |
