Ashlyn Sloane

Background: Alzheimer’s disease (AD) is classically defined by amyloid and tau pathology and is accompanied by broad disruptions in proteostasis. Heat shock proteins (HSPs) help maintain proteostasis, yet mitochondrial chaperone systems remain comparatively underexplored in AD. Hsp60 and Hsp10 form a mitochondrial chaperonin complex that folds dozens of AD-implicated mitochondrial proteins, but this client network has not been evaluated as an integrated proteostasis axis in AD. It remains unknown whether Hsp60/10 client proteins are selectively vulnerable across AD severity. Methods: We analyzed transcriptomic, proteomic, neuropathological, and cognitive data from the Religious Order Study and Memory and Aging Project (ROSMAP) to evaluate Hsp60/10 client proteins in AD. We compared Hsp60/10 clients with abundance-matched non-client mitochondrial proteins and tested differences across AD diagnostic groups and associations with Braak/tau burden, cognitive outcomes, and network centrality. These evidence layers were integrated into a candidate prioritization framework. Results: Hsp60/10 client abundance declined more strongly at the protein level than at the RNA level in late-stage AD. Compared with abundance-matched non-client mitochondrial proteins, Hsp60/10 clients showed stronger late-stage protein abundance decline. Greater late-stage client decline was associated with higher Hsp60/10 network centrality, defining a selectively vulnerable client subnetwork. Lower client abundance was associated with greater Braak/tau burden and greater cognitive impairment. Integrated prioritization nominated mitochondrial translation and TCA/pyruvate/redox clients as high-priority candidates for mechanistic follow-up. Conclusions: Together, these findings identify an Hsp60/10 client-centered mitochondrial proteostasis axis spanning mitochondrial translation and TCA/pyruvate/redox metabolism that is associated with AD severity. These findings identify a novel potential axis warranting further investigation as a mechanistic link between mitochondrial dysfunction, proteostasis, and AD.

Antibiotic resistance is a significant threat to global public health and can disproportionately affect low‐ and middle‐ income countries (LMICs). There is a lack of studies focusing on antibiotic resistance in coral reef regions and environmental reservoirs in Central America. This study followed modified World Health Organization (WHO)'s Global Tricycle Surveillance protocols for the environmental sector to address these gaps. Water samples were collected from key areas in the lower Belize River, including above and below the Belize City, an open fish market, and sewage lagoon outfall, and coral reefs. Water samples underwent qPCR analysis for a suite of antibiotic resistance gene classes (sul1, sul2, ermF, tetA, and blaSHV), intI1, and 16S rRNA. Additionally, a subset of samples were tested for extended‐spectrum β‐lactamase (ESBL) E. coli and underwent shotgun sequencing. Results show that antibiotic resistance genes (ARGs) were highest and most diverse near Belize City, particularly near the treatment lagoons and open fish market. The coral reef regions had lower levels of antibiotic resistance though not void of their presence. This study is an application of a modified Global Tricycle Surveillance protocol integrated with qPCR‐ and metagenomics‐based characterization of environmental antibiotic resistance in understudied areas. Notably, data from this study indicated that ESBL‐ E. coli could potentially be used as a screening tool for environmental antibiotic resistance, as it was only present at sites that had the highest levels of ARGs.