Alzheimer’s Disease

Yadong Huang and his collaborators are working to identify existing FDA-approved drugs that can block the effects of APOE4. They are also using “in silico” techniques to mine electronic health records for overlooked opportunities in Alzheimer’s treatment. Already, they identified one drug, bumetanide, that may prevent the disease in humans and is now in clinical testing for early Alzheimer’s. They also found that a combination of two cancer drugs also show promise against the disease.

Pioneering insights from Lennart Mucke’s lab have opened entirely new pathways for protecting brain function long before symptoms advance. Today, their novel translational models and strategies are actively accelerating the pipeline from laboratory discovery to effective treatments, offering new hope for millions affected by devastating neurological disorders worldwide.

In the lab of Jorge Palop, scientists pioneered an AI-based machine-learning tool to pinpoint otherwise-undetectable signs of early disease behavior in mice that were engineered to mimic key aspects of Alzheimer’s.

Lennart Mucke and other Gladstone investigators demonstrated that hard-to-detect, non-convulsive epileptic activity is a key feature of Alzheimer’s disease and may promote cognitive decline. They’ve demonstrated that tau-lowering drugs and certain anti-epileptic medicines can suppress brain network hyperexcitability in models of Alzheimer’s, epilepsy, and autism, leading to cognitive and behavioral benefits.

The interface between brain and blood, known as the blood-brain barrier, is more nuanced than its name suggests. It’s a boundary teeming with activity as proteins and immune cells pass to and from the brain. Andrew Yang, and his lab develop technologies to study these dynamic processes at the molecular level. By decoding how signals pass between the brain and periphery, their research is revealing key mechanisms that could promote neurodegenerative diseases such as Alzheimer’s and inform new drug delivery strategies.

Steven Finkbeiner’s team investigates how brain cells learn and remember, and what causes them to malfunction or die in disease—including Alzheimer’s, Parkinson’s, ALS, Huntington’s, autism, and schizophrenia.

The group also invented the “thinking microscope,” which designs and performs its own experiments faster and more affordably than traditional methods. The first of its kind, the AI-powered microscope has attracted collaborations with Google’s DeepMind, Microsoft Research, OpenAI, and more.

Ken Nakamura’s lab investigates how energy failure drives neurodegeneration in Alzheimer’s disease. While brain cells rely on mitochondria (the cell’s power plants) to function, they also depend on glucose and lipids for fuel. Nakamura’s team studies how APOE4—the strongest genetic risk factor for Alzheimer’s—disrupts this energy system by impairing mitochondrial function and altering how the brain uses fuel, even before symptoms appear.

To translate these findings to patients, Nakamura has partnered with UCSF on a specialized clinical trial. Using advanced brain imaging, the study tracks real-time shifts in brain metabolism in individuals with APOE4. By uncovering how energy breakdowns contribute to disease progression, his team aims to identify new biomarkers and pioneer therapies that restore metabolic health to protect brain cells.

Ryan Corces studies the genomes of individuals with Alzheimer’s to identify which genes are contributing to the disease. By mixing genomics, computational biology, and artificial intelligence, his team is sifting through millions of genetic mutations to predict which are most likely contributing. Using iPS cell-derived models, his lab is functionally testing how these mutations affect cells in order to nominate genes that could serve as prime targets for future therapies.

Jeanne Paz conducts fundamental neuroscience research to investigate how the thalamocortical system—the brain’s central hub for regulating sensory processing, attention, cognition, and sleep—misfires in Alzheimer’s and related dementias. Using optogenetics and brain-wide mapping of electrical activity, her lab identifies critical “hot spots” where abnormal neural oscillations originate and disrupt communication between subcortical structures and the cortex. Her team focuses on how the immune system hijacks the thalamocortical sleep generator circuit to cause epileptic-like discharges and disrupt sleep.