Author Type

Graduate Student

Date of Award

Fall 11-23-2025

Document Type

Thesis

Publication Status

Version of Record

Submission Date

December 2025

Department

Biomedical Science

Degree Name

Master of Science (MS)

Thesis/Dissertation Advisor [Chair]

Rui Tao

Abstract

Amyloid beta (Aβ) accumulation is a hallmark of Alzheimer’s disease (AD), persisting in the brain for years. Despite its neurotoxic potential, widespread neuronal death is not consistently observed. Histopathological analysis indicates that most neurons remain viable, suggesting an altered survival state under chronic Aβ burden. This study integrates clinical, imaging, and in vitro evidence to characterize this non-lethal state. FDG-PET imaging reveals reduced glucose metabolism. In vitro, Aβ exposure leads to decreased uptake of glucose and amino acids. Reductions in ATP levels and AMPK activity indicate impaired metabolic regulation. Despite these metabolic disruptions, cell death is not observed, implying a state of survival under nutrient stress. Atrophy may reflect synaptic loss and axonal retraction rather than neuronal loss. These findings support a model where neurons persist in a metabolically constrained but viable state.

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