Semester Award Granted

Spring 2025

Submission Date

May 2025

Document Type

Thesis

Degree Name

Master of Arts (MA)

Thesis/Dissertation Advisor [Chair]

Randy Blakely

Thesis/Dissertation Co-Chair

Robert W. Stackman

Abstract

Alzheimer’s disease (AD) involves progressive cognitive decline, with mitochondrial dysfunction, oxidative stress, and copper (Cu) imbalance implicated in its pathogenesis. MBLAC1 has been identified as a risk factor for AD in individuals with comorbid cardiovascular disease (AD-CVD). Its C. elegans ortholog, swip-10, regulates Cu ion homeostasis and mitochondrial function. To investigate MBLAC1’s role, we examined behavioral phenotypes in Mblac1 knockout (KO) mice and tested the efficacy of the Cu chaperone elesclomol (ES). Male KO mice exhibited deficits in novel object recognition (NOR), which were rescued by ES treatment. Female KOs showed increased anxiety-like behavior in the Elevated Plus Maze, though ES rescue was not pursued. Marble burying assays revealed cohort-dependent anxiety phenotypes. These findings support a role for MBLAC1 in cognitive function via Cu regulation and highlight ES as a potential therapeutic. Further studies are warranted to assess interactions with AD-associated gene mutations and to clarify MBLAC1’s contribution to AD-CVD risk.

Available for download on Wednesday, May 13, 2026

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