Lewis Honors College Capstone Collection

Year of Publication

2020

College

Arts and Sciences

Department/School/Program

Neuroscience

Degree Name

Bachelor of Science in Neuroscience

First Capstone/Thesis Advisor

Dr. Michael Murphy

Abstract

Alzheimer’s Disease (AD) is an age-related neurodegenerative disease that poses a large public health challenge due to its complex, mixed pathology. One hallmark characteristic of AD is the development of toxic neurofibrillary tau tangles (NFT), which have been associated with the neurodegenerative component of AD. There is also compelling evidence that cerebrovascular disease puts individuals at a greater risk for experiencing the cognitive decline characteristic of dementias like AD. Past research has shown that individuals suffering from cerebrovascular disease and AD (not necessarily simultaneously) display an increased expression of the sodium-hydrogen antiporter-1 (NHE1), a plasma membrane protein ubiquitously expressed throughout the human body. To further explore this relationship between NHE1, cerebrovascular disease, and tau pathology, NHE1 knockdown and control mice were administered AAV-tauP301L into the left and right ventricles via intracerebral ventricular (ICV) administration at P0/1. Pups were allowed to recover and whole brain tissue extracted after two or four weeks. Tissue was homogenized and extracted in RIPA buffer and analyzed via SDS-PAGE, followed by immunoblotting using antibodies against tau and phosphorylated tau. Identifying the role NHE1 plays in the development of tau pathology could further elucidate the mechanism relating cerebrovascular and AD tau pathology.

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