Mini-Brains Uncover a Hidden Protein That May Spark Dementia
Scientists at Ohio State University have made a surprising discovery about how brain cells may contribute to diseases like Alzheimer’s and frontotemporal dementia.
Using lab-grown “mini-brains” made from human cells, they identified a protein called GRAMD1B that helps manage cholesterol and fat inside brain cells. When this protein is out of balance, it affects important brain processes and may lead to the buildup of toxic proteins linked to dementia. The discovery offers a new clue in understanding what goes wrong in the brain and could lead to better treatments in the future.
Breakthrough in Neurodegeneration Research
Researchers at The Ohio State University Wexner Medical Center and College of Medicine have uncovered a previously unknown way that neurons contribute to neurodegeneration. Their findings are based on studies using human neural organoids – lab-grown “mini-brain” models – developed from cells of patients with frontotemporal lobar degeneration (FTLD).
This newly discovered pathway may open the door to better treatments for FTLD and Alzheimer’s disease, the two most common forms of dementia that cause progressive cognitive decline.
Mini-Brain Models Reveal Hidden Mechanisms
To investigate, scientists used advanced techniques to study neurons from both patients and mice. They grew neural organoids containing multiple types of brain cells to closely model human brain function.
Their research revealed that a protein called GRAMD1B plays a key role in regulating how neurons handle cholesterol and lipid storage. When GRAMD1B levels are disrupted, it alters cholesterol balance, lipid accumulation, and the amount of modified tau – a protein closely linked to several neurodegenerative diseases.
The study was published today (April 9) in the journal Nature Communications.
Potential for Targeted Therapies
“Scientists know that GRAMD1B plays a role in other parts of the body like the adrenal gland and intestine but until now the protein has never been studied in the brain. The findings are exciting because by targeting GRAMD1B, we can potentially develop new therapies to help people with FTLD and Alzheimer’s,” said study corresponding author Hongjun “Harry” Fu, PhD, assistant professor of neuroscience at Ohio State.
Dementia by the Numbers
About 50,000 to 60,000 Americans live with FTLD. Alzheimer’s disease is the most common cause of dementia. An estimated 6.9 million Americans who are age 65 and older are living with Alzheimer’s dementia today, according to the Alzheimer’s Association’s 2024 Alzheimer’s disease facts and figures report.
Reference: “GRAMD1B is a regulator of lipid homeostasis, autophagic flux and phosphorylated tau” by Diana Acosta Ingram, Emir Turkes, Tae Yeon Kim, Sheeny Vo, Nicholas Sweeney, Marie-Amandine Bonte, Ryan Rutherford, Dominic L. Julian, Meixia Pan, Jacob Marsh, Andrea R. Argouarch, Min Wu, Douglas W. Scharre, Erica H. Bell, Lawrence S. Honig, Jean Paul Vonsattel, Geidy E. Serrano, Thomas G. Beach, Celeste M. Karch, Aimee W. Kao, Mark E. Hester, Xianlin Han and Hongjun Fu, 9 April 2025, Nature Communications.
DOI: 10.1038/s41467-025-58585-w
The work was supported by the BrightFocus Foundation’s Alzheimer’s Disease Research, National Institute on Aging of the National Institutes of Health, The Ohio State University Chronic Brain Injury Discovery Theme pilot grant, and The Ohio State University Neurological Research Institute seed grant.