Research on nonhuman primates is making it possible to test treatments for early Alzheimer’s and similar diseases before severe brain damage occurs. A study published on June 21 in Alzheimer’s & Dementia reveals a six-month window for tracking disease progress and testing treatments in rhesus monkeys.
“This model is excellent for testing treatments that target the tau protein,” said John H. Morrison, a neurology professor at UC Davis and California National Primate Research Center and the study’s lead author.
In Alzheimer’s and other dementias, the tau protein in brain neurons spreads misfold throughout the brain. This misfolded tau disrupts brain cell functions and spreads through brain regions critical for memory and thinking.
Sick neurons trigger an inflammatory response from microglial cells. Eventually, neurons die, leaving tau protein tangles, a key marker of Alzheimer’s and other dementias.
Thanks to brain imaging, biomarkers in human fluids, and rodent studies, makes easy understanding and more about early Alzheimer’s. However, understanding how tau, inflammation, and disease progression connect remains challenging.
The macaque model helps bridge the gap between mouse studies and human patients, said Danielle Beckman, a postdoctoral researcher at UC Davis and first author of the study.
Researchers injected DNA for two mutated tau proteins into the memory-related entorhinal cortex of 12 monkeys. This area is where Alzheimer’s usually starts in humans.
Using PET, MRI, biomarkers, and microscopy, they tracked tau spread, affected cells, and inflammation in the monkeys’ brains over six months. The results show a two to six-month window to measure disease progress, allowing preclinical testing of treatments targeting tau protein.
John H. Morrison said, “We can test drugs for early-stage Alzheimer’s before dementia develops,” Early intervention is key to stopping progression.”
The paper extends previous research at the CNPRC on a nonhuman primate model. Researchers plan to combine the tau model with their existing amyloid model in future studies.
Journal reference:
- Danielle Beckman, Giovanne B. Diniz et al., Temporal progression of tau pathology and neuroinflammation in a rhesus monkey model of Alzheimer’s disease. Alzheimer’s & Dementia: The Journal of the Alzheimer’s Association. DOI: 10.1002/alz.13868.