The misfolding and accumulation of the protein fragment β-amyloid (Aβ) 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 Aβ in senile plaques and cerebral amyloid-β angiopathy as they grow old. Because the amino acid sequence of Aβ is identical in all primates studied to date, we asked whether differences in the properties of aggregated Aβ 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 Aβ fragments are largely similar in the 2 species. In addition, Aβ-rich brain extracts from the brains of aged squirrel monkeys and AD patients similarly seed the deposition of Aβ in a transgenic mouse model. However, the epitope exposure of aggregated Aβ differs in sodium dodecyl sulfate-stable oligomeric Aβ from the 2 species. In addition, the high-affinity binding of 3H Pittsburgh Compound B to Aβ 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 Aβ among primates are linked to post-translational attributes of the misfolded protein, such as molecular conformation and/or the involvement of species-specific cofactors.
|Number of pages||12|
|Journal||Neurobiology of Aging|
|State||Published - Aug 1 2016|
Bibliographical noteFunding Information:
This work was supported by P51RR165 , P51OD11132 , R21NS077049 , P30 NS050276 , P50AG025688 , and the MetLife Foundation . Additional support was provided by P01AG026423 , R21NS080576 , R21AG051266 , and the BrightFocus Foundation .
© 2016 Elsevier Inc.
- Cerebral amyloid angiopathy
- Senile plaques
ASJC Scopus subject areas
- Neuroscience (all)
- Clinical Neurology
- Developmental Biology
- Geriatrics and Gerontology