Browsing by Author "Wharton, Whitney"

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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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    Higher CSF sTNFR1-related proteins associate with better prognosis in very early Alzheimer’s disease
    (Springer Nature, 2021-06-28) Hu, William T.; Ozturk, Tugba; Kollhoff, Alexander; Wharton, Whitney; Howell, J. Christina; Alzheimer’s Disease Neuroimaging Initiative; Medicine, School of Medicine
    Neuroinflammation is associated with Alzheimer's disease, but the application of cerebrospinal fluid measures of inflammatory proteins may be limited by overlapping pathways and relationships between them. In this work, we measure 15 cerebrospinal proteins related to microglial and T-cell functions, and show them to reproducibly form functionally-related groups within and across diagnostic categories in 382 participants from the Alzheimer's Disease Neuro-imaging Initiative as well participants from two independent cohorts. We further show higher levels of proteins related to soluble tumor necrosis factor receptor 1 are associated with reduced risk of conversion to dementia in the multi-centered (p = 0.027) and independent (p = 0.038) cohorts of people with mild cognitive impairment due to predicted Alzheimer's disease, while higher soluble TREM2 levels associated with slower decline in the dementia stage of Alzheimer's disease. These inflammatory proteins thus provide prognostic information independent of established Alzheimer's markers.
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    Higher systolic blood pressure in early-mid adulthood is associated with poorer cognitive performance in those with a dominantly inherited Alzheimer’s Disease mutation but not in non-carriers. Results from the DIAN study
    (Wiley, 2023) Xu, Ying; Aung, Htein Linn; Bateman, Randall J.; Brooks, William S.; Chhatwal, Jasmeer; Day, Gregory S.; Fagan, Anne M.; Farlow, Martin R.; Gordon, Brian; Kehoe, Patrick G.; Levin, Johannes; Mori, Hiroshi; Morris, John C.; Wharton, Whitney; Humburg, Peter; Schofield, Peter R.; Peters, Ruth; Dominantly Inherited Alzheimer Network (DIAN); Neurology, School of Medicine
    Background: The Dominantly Inherited Alzheimer Network (DIAN) is a longitudinal observational study that collects data on cognition, blood pressure (BP), and other variables from autosomal-dominant Alzheimer's disease mutation carriers (MCs) and non-carrier (NC) family members in early to mid-adulthood, providing a unique opportunity to evaluate BP and cognition relationships in these populations. Method: We examined cross-sectional and longitudinal relationships between systolic and diastolic BP and cognition in DIAN MC and NC. Results: Data were available from 528 participants, who had a mean age of 38 (SD = 11) and were 42% male and 61% MCs, at a median follow-up of 2 years. Linear-multilevel models found only cross-sectional associations in the MC group between higher systolic BP and poorer performance on language (β = -0.181 [-0.318, -0.044]), episodic memory (-0.212 [-0.375, -0.049]), and a composite cognitive measure (-0.146 [-0.276, -0.015]). In NCs, the relationship was cross-sectional only and present for language alone. Discussion: Higher systolic BP was cross-sectionally but not longitudinally associated with poorer cognition, particularly in MCs. BP may influence cognition gradually, but further longitudinal research is needed.