Browsing by Author "Rexach, Jessica E."

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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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    Novel avenues of tau research
    (Wiley, 2024) Sexton, Claire E.; Bitan, Gal; Bowles, Kathryn R.; Brys, Miroslaw; Buée, Luc; Bukar Maina, Mahmoud; Clelland, Claire D.; Cohen, Ann D.; Crary, John F.; Dage, Jeffrey L.; Diaz, Kristophe; Frost, Bess; Gan, Li; Goate, Alison M.; Golbe, Lawrence I.; Hansson, Oskar; Karch, Celeste M.; Kolb, Hartmuth C.; La Joie, Renaud; Lee, Suzee E.; Matallana, Diana; Miller, Bruce L.; Onyike, Chiadi U.; Quiroz, Yakeel T.; Rexach, Jessica E.; Rohrer, Jonathan D.; Rommel, Amy; Sadri-Vakili, Ghazaleh; Schindler, Suzanne E.; Schneider, Julie A.; Sperling, Reisa A.; Teunissen, Charlotte E.; Weninger, Stacie C.; Worley, Susan L.; Zheng, Hui; Carrillo, Maria C.; Neurology, School of Medicine
    Introduction: The pace of innovation has accelerated in virtually every area of tau research in just the past few years. Methods: In February 2022, leading international tau experts convened to share selected highlights of this work during Tau 2022, the second international tau conference co-organized and co-sponsored by the Alzheimer's Association, CurePSP, and the Rainwater Charitable Foundation. Results: Representing academia, industry, and the philanthropic sector, presenters joined more than 1700 registered attendees from 59 countries, spanning six continents, to share recent advances and exciting new directions in tau research. Discussion: The virtual meeting provided an opportunity to foster cross-sector collaboration and partnerships as well as a forum for updating colleagues on research-advancing tools and programs that are steadily moving the field forward.
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    Single‐nuclei transcriptomic identifies type‐specific neuronal cell vulnerability in Amnestic and Logopenic Variant Primary Progressive Aphasia Alzheimer’s disease
    (Wiley, 2025-01-03) Pereira, Felipe Luiz; Lew, Caroline; Li, Song Hua; Rizzi, Liara; Araujo, Igor Prufer Q. C.; Soloviev, Alexander V.; Spina, Salvatore; Rexach, Jessica E.; Seeley, William W.; Suemoto, Claudia Kimie; Paraizo Leite, Renata Elaine; Newell, Kathy L.; Ghetti, Bernardino; Murray, Melissa E.; Grinberg, Lea T.; Pathology and Laboratory Medicine, School of Medicine
    Background: Individuals meeting neuropathological criteria for Alzheimer’s disease (AD) may manifest with atypical clinical syndromes. Past work showed that the neurobiological basis for these differences is related to specific neuronal vulnerabilities for tau pathology. For instance, amnestic cases have a higher burden of neurofibrillary changes in CA1. In contrast, logopenic variant primary progressive aphasia (lvPPA) cases have a higher tau burden in the superior temporal gyrus (STG). Single‐cell technology enables investigations on the molecular basis of differential neuronal vulnerability in AD. Consequently, we delved into the factors that underlie this selective vulnerability by analyzing brain samples from individuals exclusively afflicted with AD but exhibiting diverse clinical manifestations. Method: snRNA Sequencing using the Chromium Single Cell 3′ (10X Genomics, USA) on nuclei cells extracted from the CA1 sector and posterior STG of postmortem brain tissue of 48 individuals either meeting pathological criteria for AD (A3B3C3; 24 amnestic and eleven lvPPA) and healthy controls (A≤1B≤1C≤1; n = 13) (Table 1, Fig. 1A/B). Bioinformatics analyses were conducted using Cell Ranger and R software. Comparisons between cell subpopulations were conducted with the Wald statistical test, and p‐values < .05 were considered significant. Result: After quality control, we recovered more than 250k nuclei with a mean of 2,130 genes per nuclei. Upon cross‐sample alignment and t‐stochastic neighborhood embedding clustering (Fig. 1C), we found 21 excitatory neuronal subpopulations (Exc‐sub) in CA1 and 26 in STG, and 22 and 25 inhibitory neuronal subpopulations (Inh‐sub) in CA1 and STG, respectively; 16 astrocytes subpopulations in both areas and 20 microglia subpopulations in CA1 and 17 in STG (Fig. 2). One STG Exc‐sub, expressing CUX2 and LAMP5 genes showed vulnerability in lvPPA patients. Also, one STG Inh‐sub, expressing the ADARB2 gene, showed vulnerability for all AD patients. Conclusion: Our preliminary study identified a vulnerable population of excitatory neurons related to lvPPA. We are conducting validation studies using quantitative pathology to confirm these results. Furthermore, analysis of a higher number of cases is ongoing and will continue to inform on factors associated with neuronal vulnerability.