“The White Plague Seems to Love the Black Victim:” The Racialization of Tuberculosis in the Anti-Tuberculosis Campaign and Black Resistance to the “Negro Tuberculosis Problem,” 1870- 1930

Tuberculosis was one of the deadliest diseases in late nineteenth and early twentieth century America. Those most impacted by the disease were African Americans living in poverty. White public-health authorities interpreted the Black community’s susceptibility to tuberculosis as evidence of their biological inferiority. However, Black physicians, professors, club women, and nurses courageously resisted these racialized notions via academic journals, medical conferences, and periodicals. Black patients being treated in tuberculosis institutions contributed to sanatorium newspapers such as The Thermometer, establishing a voice to express their pain in ways similar to their white counterparts. Remarkably, physicians of color also found ways to care for Black tuberculosis patients with dignity in separate healthcare institutions despite inadequate funding and inferior facilities. By examining the tuberculosis epidemic during the years of 1870 to 1930, this thesis presents the success of members of the Black anti-tuberculosis movement in treating Black tuberculosis patient

The Zinc Dyshomeostasis Hypothesis of Alzheimer's Disease

Alzheimer's disease (AD) is the most common form of dementia in the elderly. Hallmark AD neuropathology includes extracellular amyloid plaques composed largely of the amyloid-β protein (Aβ), intracellular neurofibrillary tangles (NFTs) composed of hyper-phosphorylated microtubule-associated protein tau (MAP-tau), and microtubule destabilization. Early-onset autosomal dominant AD genes are associated with excessive Aβ accumulation, however cognitive impairment best correlates with NFTs and disrupted microtubules. The mechanisms linking Aβ and NFT pathologies in AD are unknown. Here, we propose that sequestration of zinc by Aβ-amyloid deposits (Aβ oligomers and plaques) not only drives Aβ aggregation, but also disrupts zinc homeostasis in zinc-enriched brain regions important for memory and vulnerable to AD pathology, resulting in intra-neuronal zinc levels, which are either too low, or excessively high. To evaluate this hypothesis, we 1) used molecular modeling of zinc binding to the microtubule component protein tubulin, identifying specific, high-affinity zinc binding sites that influence side-to-side tubulin interaction, the sensitive link in microtubule polymerization and stability. We also 2) performed kinetic modeling showing zinc distribution in extra-neuronal Aβ deposits can reduce intra-neuronal zinc binding to microtubules, destabilizing microtubules. Finally, we 3) used metallomic imaging mass spectrometry (MIMS) to show anatomically-localized and age-dependent zinc dyshomeostasis in specific brain regions of Tg2576 transgenic, mice, a model for AD. We found excess zinc in brain regions associated with memory processing and NFT pathology. Overall, we present a theoretical framework and support for a new theory of AD linking extra-neuronal Aβ amyloid to intra-neuronal NFTs and cognitive dysfunction. The connection, we propose, is based on β-amyloid-induced alterations in zinc ion concentration inside neurons affecting stability of polymerized microtubules, their binding to MAP-tau, and molecular dynamics involved in cognition. Further, our theory supports novel AD therapeutic strategies targeting intra-neuronal zinc homeostasis and microtubule dynamics to prevent neurodegeneration and cognitive decline