KHAI MẠC ĐẠI HỘI THỂ DỤC - THỂ THAO TỈNH ĐIỆN BIÊN LẦN THỨ XII, NĂM 2026

[0:00]Hello, I'm Dr. Bruce Miller. I'm a behavioral neurologist here at the Memory and Aging Center at the University of California, San Francisco. And I'm Dr. Rachel Gerson. I'm a neuropsychologist and associate director of clinical operations at the UCSF Memory and Aging Center. Welcome to our podcast Dementia Matters, where we bring together caregivers, patients, and leading researchers to discuss the latest in dementia, diagnosis, treatment, and care. Today we're pleased to welcome Dr. Sarah Kring, a post-doctoral fellow at the Memory and Aging Center. Dr. Kring, welcome to Dementia Matters. Thank you for having me. Today we're going to talk about a recent publication you've had in Neuron titled Early Immune Dysregulation in a Subset of Patients with Frontotemporal Dementia. This is a really important paper because FTD is a devastating disease and there are no treatments that change the trajectory of the illness. This is a really exciting paper because it's the first time that we've used single cell sequencing to look at what's going on in the brains of people with FTD. It's a really complex story. So let's start with some of the basics. Can you explain what FTD is and how it differs from Alzheimer's disease? Sure. So FTD or frontotemporal dementia is actually a group of disorders that are caused by the degeneration of the frontal and temporal lobes of the brain. The symptoms of FTD are very different from Alzheimer's disease, and they really depend on which part of the brain is affected. In Alzheimer's disease, the earliest symptoms are typically memory problems, but in FTD, the earliest symptoms are usually changes in behavior, personality, or language. For example, some people with FTD might become disinhibited and say or do things that are socially inappropriate. Others might become apathetic and lose interest in their hobbies or social activities. And still others might have difficulty with language, such as finding words or understanding what others are saying. It's important to note that FTD is not a rare disease. It's actually the most common cause of dementia in people under the age of 60. So it's really important to understand what's going on in the brains of these patients. That's a great overview, Sarah. So what made you decide to use single cell sequencing to study FTD? Well, we know that inflammation plays a role in many neurodegenerative diseases, including Alzheimer's disease. But in FTD, the role of inflammation is not as well understood. We wanted to get a more detailed look at what's going on at the cellular level in the brains of people with FTD. And single cell sequencing allows us to do that. It allows us to look at the gene expression in individual cells, which can give us a lot of information about what those cells are doing. So how did you go about doing this study? Can you describe your methods? Sure. So we used post-mortem brain tissue from people with FTD and healthy controls. We then isolated individual cells from the brain tissue and performed single cell RNA sequencing on them. This allowed us to look at the gene expression of thousands of individual cells from each brain. We then used computational methods to analyze the data and identify any changes in gene expression that were specific to FTD. And what did you find? We found that there was a subset of FTD patients who had a strong immune response in their brains. This immune response was characterized by an increase in the number of activated microglia, which are the brain's immune cells. We also found that these patients had an increase in the expression of genes involved in inflammation and immune signaling. So this suggests that in some FTD patients, the immune system is overactive and contributing to the disease process. That's a really interesting finding. So how does this relate to the different types of FTD? We found that this immune dysregulation was particularly prominent in patients with progranulin mutations. Progranulin is a protein that's involved in lysosomal function and inflammation. And mutations in the progranulin gene are a common cause of FTD. So this suggests that progranulin mutations might lead to FTD through an immune-mediated mechanism. That's a really important connection. So what are the implications of these findings? Well, these findings suggest that targeting the immune system might be a promising therapeutic strategy for a subset of FTD patients, particularly those with progranulin mutations. For example, we might be able to use drugs that dampen the immune response or that restore the balance of immune cells in the brain. This is exciting because it opens up new avenues for treatment development for FTD. It's also important to note that our findings highlight the importance of personalized medicine in FTD. Not all FTD patients will have the same underlying pathology, so it's important to tailor treatments to the individual patient. This is truly a groundbreaking study, Sarah. What are your next steps? We're currently working on validating these findings in a larger cohort of FTD patients. We're also interested in understanding how this immune dysregulation contributes to the cognitive and behavioral symptoms of FTD. And ultimately, we hope to translate these findings into new treatments for FTD patients. Thank you, Dr. Kring, for joining us today and for sharing your exciting research. Thank you for having me. That was Dr. Sarah Kring, a post-doctoral fellow at the UCSF Memory and Aging Center. For more information about FTD and other neurodegenerative diseases, please visit our website memory.ucsf.edu. And join us next time on Dementia Matters.