New insights into neurodegeneration using human 'mini brains'
Research findings could lead to treatments for frontotemporal lobar degeneration and Alzheimer's
- Date:
- April 9, 2025
- Source:
- Ohio State University Wexner Medical Center
- Summary:
- Researchers have discovered a new way that neurons act in neurodegeneration by using human neural organoids -- also known as 'mini-brain' models -- from patients with frontotemporal lobar degeneration (FTLD). Understanding this new pathway could help researchers find better treatments for FTLD and Alzheimer's, the two most common forms of dementia that lead to cognitive decline.
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Researchers at The Ohio State University Wexner Medical Center and College of Medicine have discovered a new way that neurons act in neurodegeneration by using human neural organoids -- also known as "mini-brain" models -- from patients with frontotemporal lobar degeneration (FTLD).
Understanding this new pathway could help researchers find better treatments for FTLD and Alzheimer's, the two most common forms of dementia that lead to cognitive decline.
Researchers used advanced techniques to study neurons from patients and mice, including growing human neural organoids ("mini brains") that can feature several cell-types found in the brain.
They found the protein GRAMD1B plays a significant role in how cholesterol and lipid stores are managed in neurons. When GRAMD1B levels are altered, it changes the balance of cholesterol, lipid stores and amount of modified tau in the cells, all of which are linked to brain diseases.
The study is published online in the journal Nature Communications.
"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.
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.
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.
The authors disclose no conflicts of interest.
Story Source:
Materials provided by Ohio State University Wexner Medical Center. Note: Content may be edited for style and length.
Journal Reference:
- 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, Hongjun Fu. GRAMD1B is a regulator of lipid homeostasis, autophagic flux and phosphorylated tau. Nature Communications, 2025; 16 (1) DOI: 10.1038/s41467-025-58585-w
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