While Alzheimer’s disease (AD) is the most common cause of dementia, thousands of people around the world suffer from another category of dementia: frontotemporal lobar degeneration, or FTLD. This type of dementia typically affects younger individuals between the ages of 45 and 64. Unlike AD, which is generally characterized by memory loss, FTLD is often characterized by changes in behavior.
Researchers at The Ohio State University Wexner Medical Center and College of Medicine studied this unique type of neurodegeneration using human neural organoids, also known as “mini-brain” models, from patients with FTLD. They discovered a new type of neuron behavior that could lead to better treatments for both FTLD and AD. Read on for more information on the study, which was published online in the journal Nature Communications.
Ohio State Researchers Explore FTLD Pathology
Like AD, there is currently no cure for FTLD. Today’s FTLD patients also lack effective treatments for their debilitating symptoms, which may include personality changes, inappropriate behavior, loss of empathy, and impulsivity.
The medical community’s understanding of FTLD relies largely on the disease’s potential genetic component. Up to 40 percent of FTLD cases involve family history, suggesting a genetic cause for the disease; in fact, researchers have linked more than a dozen genes to FTLD. These genes play a role in the dysfunction of neurons and neural circuits in the brain exhibited in FTLD.
While genes likely play a role in FTLD, two other factors — lipid dyshomeostasis and tau pathology within the brain — are slightly more puzzling. Both of these factors are present in FTLD and AD; however, the relationship between lipid dyshomeostasis and tau pathology is still unclear. The aforementioned research team sought to explore this relationship in an effort to understand and potentially mitigate harmful tau pathology in patients with FTLD.
Mini-Brain Study Identifies Potentially Druggable Protein
The Ohio State research team studied neurons from both human subjects and mouse models. Unsatisfied with a surface-level look at FTLD neurons, the team took one step further. They grew human neural organoids, also known as “mini-brains,” in an effort to more closely observe unique cell types found in the brain. The team found that the protein GRAMD1B plays a significant role in how both cholesterol and lipid stores are managed in neurons.
Officially known as a GRAM domain containing 1B, GRAMD1B is known for its role in cholesterol-binding activity and cholesterol transfer activity. The research team noted that when GRAMD1B levels are altered, it changes the balance of cholesterol, lipid stores, and modified tau in the cells. Each of these components is linked to neurologic disease. Thus, GRAMD1B has emerged as a potentially druggable target for neurodegenerative conditions like FTLD and AD.
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“Scientists know that GRAMD1 B 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,” wrote study corresponding author Hongjun Fu, PhD, assistant professor of neuroscience at Ohio State. Fu added: “The findings are exciting because by targeting GRAMD1B, we can potentially develop new therapies to help people with FTLD and Alzheimer’s.”
In addition to its in vivo models of tau pathology, Scantox Neuro offers several in vitro models to study tau phosphorylation, toxicity, aggregation, uptake, and seeding. Furthermore, cerebral organoids can be used for your research approaches.
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