| First Author | Olsson TT | Year | 2018 |
| Journal | Neurobiol Dis | Volume | 113 |
| Pages | 1-10 | PubMed ID | 29414379 |
| Mgi Jnum | J:348500 | Mgi Id | MGI:6142550 |
| Doi | 10.1016/j.nbd.2018.01.015 | Citation | Olsson TT, et al. (2018) Prion-like seeding and nucleation of intracellular amyloid-beta. Neurobiol Dis 113:1-10 |
| abstractText | Alzheimer''s disease (AD) brain tissue can act as a seed to accelerate aggregation of amyloid-beta (Abeta) into plaques in AD transgenic mice. Abeta seeds have been hypothesized to accelerate plaque formation in a prion-like manner of templated seeding and intercellular propagation. However, the structure(s) and location(s) of the Abeta seeds remain unknown. Moreover, in contrast to tau and alpha-synuclein, an in vitro system with prion-like Abeta has not been reported. Here we treat human APP expressing N2a cells with AD transgenic mouse brain extracts to induce inclusions of Abeta in a subset of cells. We isolate cells with induced Abeta inclusions and using immunocytochemistry, western blot and infrared spectroscopy show that these cells produce oligomeric Abeta over multiple replicative generations. Further, we demonstrate that cell lysates of clones with induced oligomeric Abeta can induce aggregation in previously untreated N2a APP cells. These data strengthen the case that Abeta acts as a prion-like protein, demonstrate that Abeta seeds can be intracellular oligomers and for the first time provide a cellular model of nucleated seeding of Abeta. |
