"The microglial response affects neurons which then affects the capacity to learn and form new memories,” Landreth said.Įxtensive collaboration within Stark Neurosciences Research Institute enabled a comprehensive evaluation of the gene's implications. Microglia, often regarded as the brain's first line of defense against infections, toxins and damage, has garnered attention for its significant role in influencing disease susceptibility. The study unveiled specific gene clusters orchestrating these alterations in immune cell behavior within microglia. Immune cells harboring risk-reducing gene variants demonstrated a reduction in amyloid plaques, while those carrying the risk-elevating variants exhibited a surge in plaque accumulation. Innovative mouse models of Alzheimer's disease developed by the NIH-funded MODEL-AD Center allowed researchers to substantiate their findings. The study found that the M28L variant heightened the susceptibility to Alzheimer's disease, whereas the P522R variant exhibited a risk-reducing effect. This genetic anomaly, discovered through analysis of the gene's biological workings, showcased the impact of specific rare variants. The focal point of the investigation revolved around the phospholipase C gamma 2 (PLCG2) gene, intricately entwined within microglia-central to the brain's immune response. Tsai, now a postdoctoral fellow at Stanford University Medical School, has significantly contributed to unraveling the mysteries of Alzheimer's disease. Their research was recently published in the journal Immunity.Īndy Tsai, PhD, a graduate of the Medical Neurosciences Graduate Program, was the driving force behind the research, encompassing his PhD thesis. The research team included several IU investigators within Stark Neurosciences Research Institute- Gary Landreth, PhD, the Martin Professor of Alzheimer’s Research Bruce Lamb, PhD, executive director of Stark Neuroscience Research Institute Stephanie Bissel, PhD, assistant professor of genetics Kwangsik Nho, PhD, associate professor of radiology and imaging sciences and Adrian Oblak, PhD, assistant professor of radiology and imaging sciences. The team's research, rooted in human genetics studies, has unearthed a critical mutation within a key gene operating in the brain's immune cells, potentially elevating the risk of Alzheimer's disease. INDIANAPOLIS-A groundbreaking study led by experts from Indiana University School of Medicine has shed new light on the genetic underpinnings of Alzheimer's disease.
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