Research in nonhuman primates is opening new possibilities for testing treatments for early-stage Alzheimer’s disease and similar conditions before extensive brain cell death and dementia set in. A recent study published in Alzheimer’s & Dementia: The Journal of the Alzheimer’s Association reveals a six-month window during which disease progression can be tracked and treatments tested in rhesus macaques. 

“This is a very powerful translational model to test interventions that target the tau protein,” said John H. Morrison, professor of neurology at the University of California, Davis, and California National Primate Research Center, and corresponding author on the paper. 

 The Role of Tau Protein in Alzheimer’s Disease 

The tau protein, found in neurons, is implicated in Alzheimer’s disease, frontotemporal dementia, and other dementias. Misfolded tau disrupts essential brain cell functions, spreading through connected regions of the cortex that are crucial for memory and cognition. This leads to an inflammatory response and eventually neuron death. 

Advances in brain imaging, biomarkers in human serum and cerebrospinal fluid, and rodent models have improved our understanding of early-stage Alzheimer’s. However, the relationship between tau, inflammation, and disease progression remains complex. The macaque model bridges the gap between mouse models and human patients, better representing the disease’s progression. 

The Six-Month Window for Disease Progression 

In the study, researchers injected a vector carrying DNA for two mutated tau proteins into the entorhinal cortex of 12 monkeys. This brain region, involved with memory, is where Alzheimer’s typically originates in humans. Over six months, they tracked the spread of tau protein, affected cells, and inflammation using PET and MRI imaging, biomarkers, and microscopy. 

The results indicate a window of at least two to six months where disease progress can be measured, allowing for preclinical testing of interventions targeting the tau protein. “We can look at drugs targeting early-stage Alzheimer’s before dementia develops,” Morrison said. “It’s all about early intervention to arrest progression.” 

This study builds on earlier work at the CNPRC establishing the nonhuman primate model. Future research will combine the tau model with existing systems based on amyloid, further enhancing our understanding and treatment of Alzheimer’s disease.