Stephen Wong, Houston Methodist Research Institute -…

How does obesity in midlife affect your chances of developing Alzheimer’s disease?

Stephen Wong, professor of radiology and medicine at the Houston Methodist Research Institute, looks into the links.

Faculty Bio:

Dr. Wong holds the John S. Dunn Presidential Distinguished Chair in Biomedical Engineering and is a Professor of Radiology and Medicine with Tenure and Chief of Medical Physics at Houston Methodist. He is renowned for his groundbreaking contributions across multiple disciplines, including medical imaging, life sciences, finance, and technology.

At Houston Methodist, Wong founded several key centers and labs, including the Division of Shared Resources at Houston Methodist Neal Cancer Center, the Ting Tsung and Wei Fong Chao Center for BRAIN, the Advanced Cellular and Tissue Microscopy Core, the Translational Biophotonics Lab, the Center for Modeling Cancer Development, the AI in Innovative Medicine lab, and Systems Medicine and Bioengineering Department. His research has been consistently funded by NIH for three decades. He has published over 500 peer-reviewed scientific papers and five books. He has trained and mentored over 170 Ph.D., MD/Ph.D., and postdocs, with four now holding endowed chairs or distinguished professor positions.

Dr. Wong’s research focuses on a systems-based understanding of health and disease to develop cost-effective strategies for disease management and healthcare delivery. The mission of his lab is to engineer medicine and biology, discovering novel drugs and biomarkers and developing advanced diagnostic and therapeutic devices.

The research emphasizes improving the detection, diagnosis, treatment, and prevention of cancer, neurological disorders, and metabolic diseases. Current projects include understanding and targeting micro- and macroenvironments of cancer and Alzheimer’s disease, applying spatial and systems biology methods for drug and biomarker discovery in cancer and neurodegenerative diseases, creating label-free point-of-care molecular diagnosis and interventional devices, and developing novel artificial intelligence applications to transform the triage, diagnosis, treatment of strokes and related disorders.

Transcript:

Researchers have long recognized midlife obesity as a major modifiable risk factor for Alzheimer's disease. But how does a metabolic disorder that begins outside the brain drive neurodegeneration inside it? Our team set out to find that missing link. What's new is that obesity doesn't just raise Alzheimer's risk generally — it alters specific lipid pathways affecting brain immune cells and neurons, revealing a mechanism we may be able to target.

We found that obesity disrupts the balance of phosphatidylethanolamine, or PE, an essential membrane lipid that helps brain cells communicate, respond to stress, and maintain function. Abnormal PE accumulation remodels cell membranes and disrupts communication between metabolic tissues, brain immune cells, and neurons. As PE rises, immune cells become less effective at protecting healthy tissue, while neurons show more stress and produce more Alzheimer's-associated toxic proteins — together accelerating disease progression.

This reframes obesity not just as a risk factor, but as a biologically actionable disease modifier — opening the door to earlier detection, metabolism-informed biomarkers, and therapies that target these mechanisms before irreversible brain damage occurs.

To uncover this, we integrate a systems medicine approach that allows us to connect metabolic imbalance with specific brain-cell behaviors. Looking ahead, we aim to combine AI and multi-omics to identify drug candidates and accelerate precision therapies that preserve brain health before memory loss begins.

Stephen Wong, Houston Methodist Research Institute - Obesity's Association with Neurodegeneration