Browsing by Author "Bradshaw, Elizabeth M."

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    Advancements in Immunity and Dementia Research: Highlights from the 2023 AAIC Advancements: Immunity Conference
    (Wiley, 2025) Kloske, Courtney M.; Mahinrad, Simin; Barnum, Christopher J.; Batista, Andre F.; Bradshaw, Elizabeth M.; Butts, Brittany; Carrillo, Maria C.; Chakrabarty, Paramita; Chen, Xiaoying; Craft, Suzanne; Da Mesquita, Sandro; Dabin, Luke C.; Devanand, Davangere; Duran-Laforet, Violeta; Elyaman, Wassim; Evans, Elizabeth E.; Fitzgerald-Bocarsly, Patricia; Foley, Kate E.; Harms, Ashley S.; Heneka, Michael T.; Hong, Soyon; Huang, Yu-Wen A.; Jackvony, Stephanie; Lai, Laijun; Le Guen, Yann; Lemere, Cynthia A.; Liddelow, Shane A.; Martin-Peña, Alfonso; Orr, Anna G.; Quintana, Francisco J.; Ramey, Grace D.; Rexach, Jessica E.; Rizzo, Stacey J. S.; Sexton, Claire; Tang, Alice S.; Torrellas, Jose G.; Tsai, Andy P.; van Olst, Lynn; Walker, Keenan A.; Wharton, Whitney; Tansey, Malú Gámez; Wilcock, Donna M.; Medical and Molecular Genetics, School of Medicine
    The immune system is a key player in the onset and progression of neurodegenerative disorders. While brain resident immune cell-mediated neuroinflammation and peripheral immune cell (eg, T cell) infiltration into the brain have been shown to significantly contribute to Alzheimer's disease (AD) pathology, the nature and extent of immune responses in the brain in the context of AD and related dementias (ADRD) remain unclear. Furthermore, the roles of the peripheral immune system in driving ADRD pathology remain incompletely elucidated. In March of 2023, the Alzheimer's Association convened the Alzheimer's Association International Conference (AAIC), Advancements: Immunity, to discuss the roles of the immune system in ADRD. A wide range of topics were discussed, such as animal models that replicate human pathology, immune-related biomarkers and clinical trials, and lessons from other fields describing immune responses in neurodegeneration. This manuscript presents highlights from the conference and outlines avenues for future research on the roles of immunity in neurodegenerative disorders. HIGHLIGHTS: The immune system plays a central role in the pathogenesis of Alzheimer's disease. The immune system exerts numerous effects throughout the brain on amyloid-beta, tau, and other pathways. The 2023 AAIC, Advancements: Immunity, encouraged discussions and collaborations on understanding the role of the immune system.
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    Neuropathological correlates and genetic architecture of microglial activation in elderly human brain
    (Springer Nature, 2019-01-24) Felsky, Daniel; Roostaei, Tina; Nho, Kwangsik; Risacher, Shannon L.; Bradshaw, Elizabeth M.; Petyuk, Vlad; Schneider, Julie A.; Saykin, Andrew; Bennett, David A.; De Jager, Philip L.; Radiology and Imaging Sciences, School of Medicine
    Microglia, the resident immune cells of the brain, have important roles in brain health. However, little is known about the regulation and consequences of microglial activation in the aging human brain. Here we report that the proportion of morphologically activated microglia (PAM) in postmortem cortical tissue is strongly associated with β-amyloid, tau-related neuropathology, and the rate of cognitive decline. Effect sizes for PAM measures are substantial, comparable to that of APOE ε4, the strongest genetic risk factor for Alzheimer's disease, and mediation models support an upstream role for microglial activation in Alzheimer's disease via accumulation of tau. Further, we identify a common variant (rs2997325) influencing PAM that also affects in vivo microglial activation measured by [11C]-PBR28 PET in an independent cohort. Thus, our analyses begin to uncover pathways regulating resident neuroinflammation and identify overlaps of PAM's genetic architecture with those of Alzheimer's disease and several other traits.