| First Author | Rosen RF | Year | 2016 |
| Journal | Neurobiol Aging | Volume | 44 |
| Pages | 185-196 | PubMed ID | 27318146 |
| Mgi Jnum | J:239036 | Mgi Id | MGI:5824798 |
| Doi | 10.1016/j.neurobiolaging.2016.04.019 | Citation | Rosen RF, et al. (2016) Comparative pathobiology of beta-amyloid and the unique susceptibility of humans to Alzheimer's disease. Neurobiol Aging 44:185-196 |
| abstractText | The misfolding and accumulation of the protein fragment beta-amyloid (Abeta) is an early and essential event in the pathogenesis of Alzheimer's disease (AD). Despite close biological similarities among primates, humans appear to be uniquely susceptible to the profound neurodegeneration and dementia that characterize AD, even though nonhuman primates deposit copious Abeta in senile plaques and cerebral amyloid-beta angiopathy as they grow old. Because the amino acid sequence of Abeta is identical in all primates studied to date, we asked whether differences in the properties of aggregated Abeta might underlie the vulnerability of humans and the resistance of other primates to AD. In a comparison of aged squirrel monkeys (Saimiri sciureus) and humans with AD, immunochemical and mass spectrometric analyses indicate that the populations of Abeta fragments are largely similar in the 2 species. In addition, Abeta-rich brain extracts from the brains of aged squirrel monkeys and AD patients similarly seed the deposition of Abeta in a transgenic mouse model. However, the epitope exposure of aggregated Abeta differs in sodium dodecyl sulfate-stable oligomeric Abeta from the 2 species. In addition, the high-affinity binding of (3)H Pittsburgh Compound B to Abeta is significantly diminished in tissue extracts from squirrel monkeys compared with AD patients. These findings support the hypothesis that differences in the pathobiology of aggregated Abeta among primates are linked to post-translational attributes of the misfolded protein, such as molecular conformation and/or the involvement of species-specific cofactors. |
