Dissertations and Theses (Open Access)

Author ORCID Identifier

0009-0001-6561-5781

Date of Graduation

8-2026

Document Type

Thesis (MS)

Program Affiliation

Biomedical Sciences

Degree Name

Masters of Science (MS)

Advisor/Committee Chair

Harry Karmouty-Quintana

Committee Member

Tingting Mills

Committee Member

Rodrigo Morales

Committee Member

Sean Marrelli

Committee Member

Callie Kwartler

Abstract

Cerebrovascular remodeling commonly coexists with Alzheimer's disease (AD), yet the mechanisms by which vascular dysfunction contribute to AD progression remain unclear. One potential mechanism linking vascular dysfunction and AD is reduced expression of Nudix hydrolase 21 (Nudt21). In the present study, we investigated whether smooth muscle cell (SMC)-specific Nudt21 depletion promotes cerebrovascular remodeling and whether these vascular changes exacerbate AD-related pathology. Our results demonstrated that SMC-specific Nudt21 depletion led to inward cerebrovascular remodeling, characterized by increased vessel wall thickness, reduced lumen diameter, and an elevated SMA area-to-lumen diameter ratio. In heterozygous Tg-SwDI mice, Nudt21 depletion exacerbated hippocampal Aβ accumulation and reduced locomotor activity. Moreover, our findings suggest that cerebrovascular remodeling may influence locomotor activity through both direct effects of vascular structural changes and indirect effects mediated by increased Aβ burden. Collectively, these findings support an active role for vascular smooth muscle cells in AD progression and identify Nudt21 as a promising upstream regulator linking vascular remodeling and AD pathology, highlighting it as a potential therapeutic target for future interventions.

Keywords

Nudix hydrolase 21, Alzheimer's disease, Vascular remodeling, Smooth muscle cells

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Available for download on Tuesday, July 27, 2027

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