Date of Award

2016

Document Type

Thesis

Degree Name

Bachelors

Department

Natural Sciences

First Advisor

Beulig, Alfred

Area of Concentration

Neurobiology

Abstract

Alzheimer's Disease (AD) is the leading cause of dementia in humans. AD is characterized by the accumulation and aggregation of beta amyloid peptide (AB) to form senile plaques, tau hypherphosphorylation and aggregation, and rampant neuroinflammation. An emerging view, pioneered in part by The Roskamp Institute's Dr. Daniel Paris, suggests an overactive immune system in the brain as the culprit. Recent research has brought to light spleen tyrosine kinase (SYK) as a major mediator of the neuroinflammation present in AD. Two investigations were performed: the first examined the effects of in vitro SYK inhibition on tau hyperphosphorylation in "healthy" and inflamed SH-SY5Y cell cultures. The second investigation sought to identify & localize activated SYK in the brains of healthy and transgenic APP and PSAPP AD-model mice. SYK inhibition lowered tau hyperphosphorylation in vitro, and activated SYK was found to localize with microglia but not astrocytes in the brains of mice with AD pathology. Further experiments are suggested to understand the potential for P-SYK presence in degenerating neurites, and to further implicate the magnitude of its role in Alzheimer's Disease and other autoimmune disorders.

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