| First Author | Manassero G | Year | 2016 |
| Journal | Aging Cell | Volume | 15 |
| Issue | 5 | Pages | 914-23 |
| PubMed ID | 27406053 | Mgi Jnum | J:236553 |
| Mgi Id | MGI:5806372 | Doi | 10.1111/acel.12500 |
| Citation | Manassero G, et al. (2016) Beta-amyloid 1-42 monomers, but not oligomers, produce PHF-like conformation of Tau protein. Aging Cell 15(5):914-23 |
| abstractText | The mechanistic relationship between amyloid beta1-42 (Abeta1-42) and the alteration of Tau protein are debated. We investigated the effect of Abeta1-42 monomers and oligomers on Tau, using mice expressing wild-type human Tau that do not spontaneously develop Tau pathology. After intraventricular injection of Abeta1-42, mice were sacrificed after 3 h or 4 days. The short-lasting treatment with Abeta monomers, but not oligomers, showed a conformational PHF-like change of Tau, together with hyperphosphorylation. The same treatment induced increase in concentration of GSK3 and MAP kinases. The inhibition of the kinases rescued the Tau changes. Abeta monomers increased the levels of total Tau, through the inhibition of proteasomal degradation. Abeta oligomers reproduced all the aforementioned alterations only after 4 days of treatment. It is known that Abeta1-42 monomers foster synaptic activity. Our results suggest that Abeta monomers physiologically favor Tau activity and dendritic sprouting, whereas their excess causes Tau pathology. Moreover, our study indicates that anti-Abeta therapies should be targeted to Abeta1-42 monomers too. |
