Browsing by Author "Hu, William T."

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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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    NMR metabolomics of cerebrospinal fluid differentiates inflammatory diseases of the central nervous system
    (PLOS, 2018-12-17) French, Caitlin D.; Willoughby, Rodney E.; Pan, Amy; Wong, Susan J.; Foley, John F.; Wheat, L. Joseph; Fernandez, Josefina; Encarnacion, Rafael; Ondrush, Joanne M.; Fatteh, Naaz; Paez, Andres; David, Dan; Javaid, Waleed; Amzuta, Ioana G.; Neilan, Anne M.; Robbins, Gregory K.; Brunner, Andrew M.; Hu, William T.; Mishchuk, Darya O.; Slupsky, Carolyn M.; Medicine, School of Medicine
    BACKGROUND: Myriad infectious and noninfectious causes of encephalomyelitis (EM) have similar clinical manifestations, presenting serious challenges to diagnosis and treatment. Metabolomics of cerebrospinal fluid (CSF) was explored as a method of differentiating among neurological diseases causing EM using a single CSF sample. METHODOLOGY/PRINCIPAL FINDINGS: 1H NMR metabolomics was applied to CSF samples from 27 patients with a laboratory-confirmed disease, including Lyme disease or West Nile Virus meningoencephalitis, multiple sclerosis, rabies, or Histoplasma meningitis, and 25 controls. Cluster analyses distinguished samples by infection status and moderately by pathogen, with shared and differentiating metabolite patterns observed among diseases. CART analysis predicted infection status with 100% sensitivity and 93% specificity. CONCLUSIONS/SIGNIFICANCE: These preliminary results suggest the potential utility of CSF metabolomics as a rapid screening test to enhance diagnostic accuracies and improve patient outcomes.
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    Perspective on the "African American participation in Alzheimer disease research: Effective strategies" workshop, 2018
    (Wiley, 2020-12) Denny, Andrea; Streitz, Marissa; Stock, Kristin; Balls-Berry, Joyce E.; Barnes, Lisa L.; Byrd, Goldie S.; Croff, Raina; Gao, Sujuan; Glover, Crystal M.; Hendrie, Hugh C.; Hu, William T.; Manly, Jennifer J.; Moulder, Krista L.; Stark, Susan; Thomas, Stephen B.; Whitmer, Rachel; Wong, Roger; Morris, John C.; Lingler, Jennifer H.; Psychiatry, School of Medicine
    The Washington University School of Medicine Knight Alzheimer Disease Research Center's "African American Participation in Alzheimer Disease Research: Effective Strategies" Workshop convened to address a major limitation of the ongoing scientific progress regarding Alzheimer's disease and related dementias (ADRD): participants in most ADRD research programs overwhelmingly have been limited to non-Hispanic white persons, thus precluding knowledge as to how ADRD may be represented in non-white individuals. Factors that may contribute to successful recruitment and retention of African Americans into ADRD research were discussed and organized into actionable next steps as described within this report.