Graduation Year

2026

Date of Submission

4-2026

Document Type

Campus Only Senior Thesis

Degree Name

Bachelor of Arts

Department

Neuroscience

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Abstract

Alzheimer’s Disease remains a leading driver of the global dementia crisis, characterized by the progressive accumulation of toxic amyloid-beta plaques and the eventual functional exhaustion of microglia. Protein Tyrosine Phosphatase 1B has been identified as a critical molecular "brake" that disrupts microglial phagocytosis and exacerbates neuroinflammation. This study characterizes the naturally derived aminosterol Claramine as a therapeutic candidate capable of inhibiting this enzyme and reinvigorating the brain’s immune response. Utilizing a bEnd.3 in vitro Transwell model and in vivo CM puncture, we confirmed that Claramine successfully crosses the blood-brain barrier without compromising endothelial integrity, reaching peak cerebrospinal fluid concentrations shortly after administration. Biochemical and Western Blot analyses demonstrated that Claramine acts as a potent inhibitor of the enzyme, effectively restoring insulin receptor and AKT survival signaling in hippocampal tissue. Furthermore, real-time live-cell imaging revealed that Claramine treatment significantly rescues microglial phagocytic function, leading to a substantial increase in amyloid-beta clearance compared to vehicle-treated controls. These findings suggest that by "unbraking" the immune system, Claramine offers a promising, resilient strategy for addressing the underlying molecular pathology of sporadic Alzheimer’s Disease.

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