| First Author | Uhlmann RE | Year | 2020 |
| Journal | Nat Neurosci | Volume | 23 |
| Issue | 12 | Pages | 1580-1588 |
| PubMed ID | 33199898 | Mgi Jnum | J:299949 |
| Mgi Id | MGI:6501431 | Doi | 10.1038/s41593-020-00737-w |
| Citation | Uhlmann RE, et al. (2020) Acute targeting of pre-amyloid seeds in transgenic mice reduces Alzheimer-like pathology later in life. Nat Neurosci 23(12):1580-1588 |
| abstractText | Amyloid-beta (Abeta) deposits are a relatively late consequence of Abeta aggregation in Alzheimer's disease. When pathogenic Abeta seeds begin to form, propagate and spread is not known, nor are they biochemically defined. We tested various antibodies for their ability to neutralize Abeta seeds before Abeta deposition becomes detectable in Abeta precursor protein-transgenic mice. We also characterized the different antibody recognition profiles using immunoprecipitation of size-fractionated, native, mouse and human brain-derived Abeta assemblies. At least one antibody, aducanumab, after acute administration at the pre-amyloid stage, led to a significant reduction of Abeta deposition and downstream pathologies 6 months later. This demonstrates that therapeutically targetable pathogenic Abeta seeds already exist during the lag phase of protein aggregation in the brain. Thus, the preclinical phase of Alzheimer's disease-currently defined as Abeta deposition without clinical symptoms-may be a relatively late manifestation of a much earlier pathogenic seed formation and propagation that currently escapes detection in vivo. |
