| First Author | Klementieva O | Year | 2017 |
| Journal | Nat Commun | Volume | 8 |
| Pages | 14726 | PubMed ID | 28287086 |
| Mgi Jnum | J:244385 | Mgi Id | MGI:5913164 |
| Doi | 10.1038/ncomms14726 | Citation | Klementieva O, et al. (2017) Pre-plaque conformational changes in Alzheimer's disease-linked Abeta and APP. Nat Commun 8:14726 |
| abstractText | Reducing levels of the aggregation-prone Abeta peptide that accumulates in the brain with Alzheimer's disease (AD) has been a major target of experimental therapies. An alternative approach may be to stabilize the physiological conformation of Abeta. To date, the physiological state of Abeta in brain remains unclear, since the available methods used to process brain tissue for determination of Abeta aggregate conformation can in themselves alter the structure and/or composition of the aggregates. Here, using synchrotron-based Fourier transform infrared micro-spectroscopy, non-denaturing gel electrophoresis and conformational specific antibodies we show that the physiological conformations of Abeta and amyloid precursor protein (APP) in brain of transgenic mouse models of AD are altered before formation of amyloid plaques. Furthermore, focal Abeta aggregates in brain that precede amyloid plaque formation localize to synaptic terminals. These changes in the states of Abeta and APP that occur prior to plaque formation may provide novel targets for AD therapy. |
