Rethinking Alzheimer’s disease one gene, one patient at a time
Like so many people, Joshua Shulman, M.D., Ph.D., director of the Center for Alzheimer’s and Neurodegenerative Diseases (CAND) at Baylor College of Medicine, experienced Alzheimer’s disease up close as a teenager while his grandfather struggled with the condition. Dr. Shulman was both struck by the limited treatments available and fascinated by the unsolved complexity, which motivated him to become a physician-scientist to tackle conditions like Alzheimer’s from different angles and bridge the worlds of research and patient care.
This unique perspective is helping him lead a paradigm shift in our collective understanding of Alzheimer’s: instead of a single disease, what if Alzheimer’s is a collection of varied conditions driven by distinct genetic and biological pathways?
The significant heterogeneous nature of Alzheimer’s complicates diagnosis, management and treatment, something that Dr. Shulman sees when treating patients seeking care for Alzheimer’s and other disorders.
“I’m reminded every week while in clinic what patients with neurodegenerative diseases and their families are dealing with,” said Dr. Shulman, who also serves as a professor of Neurology, Neuroscience and Molecular and Human Genetics at Baylor and the Co-Director of the Jan and Dan Duncan Neurological Research Institute at Texas Children’s Hospital.
Recent discoveries have identified hundreds of genes tied to Alzheimer’s risk, though most of their roles were unclear—until now. In a study published in October 2025, Dr. Shulman’s team used fruit flies, which share key genetic traits with humans, to test 100 Alzheimer’s risk genes. They found these genes can variably affect brain health by impacting structure, electrical activity or stress response, suggesting that people may develop Alzheimer’s through distinct biological pathways and perhaps explaining some of its heterogeneous manifestations and why treatments don’t work equally well for everyone. This study also provides a roadmap for future research into genetic risk factors and developing more personalized therapies.
Pursuing personalized therapies is exactly what Dr. Shulman aims to do as the director of the CAND, established by Baylor in 2020. One of the CAND’s most powerful tools is its Precision Medicine Core, which provides patients and research volunteers with comprehensive clinical and molecular characterization that pinpoints risk factors, resolves heterogeneity and provides counseling for individualized diagnosis and management.
Dr. Shulman plans to pursue longitudinal follow-up studies of more than 200 Houston-area participants, including cognitive testing, blood biomarker analysis, neuroimaging and whole genome sequencing. The project recruits participants both with and without memory or other symptoms. The study has already been able to identify some individuals with completely normal cognition but showing early evidence of Alzheimer’s biomarkers. This not only allowed Dr. Shulman and colleagues to identify promising novel targets for laboratory investigation but also to refer participants for cutting-edge clinical trials of preventative therapies, intervening before the onset of symptoms.
Dr. Shulman sees it as a bold new frontier. “Now that we’re evolving in our understanding of how Alzheimer’s can present differently in patients, we can start developing treatments that actually address the underlying causes.” Dr. Shulman said. “This is the dawn of precision medicine.”
