Alzheimer's is the most common form of age-dependent dementia and represents a significant global health burden. Despite this, its causes and mechanisms remain incompletely understood and traditional biomedical research has often been plagued by translational failures. This is due partly to the fact that biomedical research often relies on mice or other model organisms separated from humans by many millions of years.

We therefore take a comparative approach, using human and nonhuman primate iPSC-derived neurons to identify species-specific differences that may leave humans more vulnerable to Alzheimer’s disease processes. Thus far, our work has revealed species differences in vulnerability to toxicity induced by amyloid-beta and tau, the two proteins whose aggregates form the hallmark pathologies of the disease.   

Interest in tau’s role in Alzheimer’s pathobiology has grown in recent years, in part because tau burden is closely correlated with disease progression. Interestingly, tau pathologies are relatively rare in nonhuman primates, making it a promising avenue for investigating species-specific differences underlying human disease vulnerability. Our current work therefore focuses on dissecting the mechanisms underlying variations in tau vulnerability, as well as identifying differences in endogenous tau secretion.

Led by:
Isabel August, PhD
Postdoctoral Researcher – Marchetto Lab, UC San Diego