You study blood-based biomarkers that indicate the presence of Alzheimer’s disease. Can you explain how this can help lead to treatments?

At the moment, to treat Alzheimer’s disease, the field is operating with a one-size-size-fits-all approach, prescribing similar drugs and treatment plans to anyone with the disease. That’s not the best way to have the most successful medicines or the most successful therapies.

In somebody who has lived to 70 years old, there are often many different pathologies that are happening at once. Using new technologies that are allowing unprecedented glimpses into the underlying biology, my lab is studying molecules in the blood to very precisely measure and build a fingerprint of a patient’s individual pathologies. That way, as new therapies come online, we'll be able to identify which pathologies need to be targeted as well as to measure the response of experimental therapeutics targeting these pathologies.

We’re also developing some of these therapeutics ourselves. Work from my lab has identified modifications to the brain’s immune cells that appear to make them resistant to the accumulation of amyloid beta, one of the toxic proteins that builds up in the brain in Alzheimer’s disease. In one project, we are focusing on how we might boost neuroimmune metabolic homeostasis and harness it as a tool to insulate the brain against Alzheimer’s disease pathology. 

In addition to your research at the molecular level, you make use of clinical cohorts in unique ways. Can you tell us about that?

It used to be that you compared large cohorts of Alzheimer’s disease patients to control groups to look for differences that might indicate hallmarks of disease. Instead, my lab is looking at resilience factors in a sample size of one: an individual resistant to a “guaranteed” form of Alzheimer’s disease. 

There are individual families with a genetic predisposition that essentially guarantees that they will develop Alzheimer's disease. The age of onset of the parent is remarkably close to the expected age of onset of the individual in the next generation. So we can estimate with very high accuracy when we expect the individual to develop symptoms. And in a very small number of people in these families, we see that they are somehow able to avoid developing Alzheimer's disease. We're really interested in understanding what those mechanisms are, to use that as a way to generate new therapeutic strategies. 

We have recently identified a resilient individual and will be publishing a case study.

How does your work complement the research of Salame-Feraud Director of the Center for Alzheimer's Disease Research Bess Frost? 

There is a lot of overlap in terms of the overall goals of disease modification that we share. 

For example, my lab could help interpret biomarker responses for the Frost lab’s future clinical trials. Something that I've done at Stanford is pre-screen participants to only allow individuals who have Alzheimer's disease biomarkers to be randomized into a clinical trial as either treatment or placebo. That's incredibly important because past trials have included people who may have dementia, but who don't actually have an Alzheimer's disease diagnosis, and that really diminishes researchers’ abilities to assess a drug's performance. 

The Frost lab will also be able to use the new biomarkers of synaptic integrity, or healthy connections between neurons, that my lab identifies as outcomes for the efficacy of the drugs they’re evaluating. 

What attracted you to Brown?

It is important for me to be somewhere with a strong history of basic research, and also very strong translational capabilities. My future colleagues made it very clear that that's what the position was–they were looking for somebody to identify druggable targets for Alzheimer's disease to initiate and allow clinical trials. 

I'm very grateful to be here and excited to be setting up the lab together with my laboratory research coordinator, Justin Mendiola, who is relocating from Stanford with me.