Graduation Year

2020

Document Type

Thesis

Degree

M.S.

Degree Name

Master of Science (M.S.)

Degree Granting Department

Medical Sciences

Major Professor

Mark Kindy, Ph.D., FAHA

Committee Member

Manas Biswal, M.F.Sc, Ph.D.

Committee Member

Vijay Sutariya, PharmD

Keywords

inflammation, neurodegenerative disease, p-tau, traumatic brain injury

Abstract

Serum amyloid P (SAP) component is a glycoprotein that is a major constituent of human serum. SAP has been recognized to stimulate amyloid fibrillogenesis. One way that SAP can be transported to the brain is by passing through the blood brain barrier (BBB). Traumatic brain injury (TBI) and repeated or severe non-penetrating head injury, can escalate the exposure of the brain to SAP, which in turn can contribute to neurodegeneration. TBI can lead to chronic traumatic encephalopathy (CTE) which is a neuropathological condition that has been found in people who have been exposed to repeated head injuries or impacts. In order to determine the role that SAP plays in the pathogenesis of SAP, brain samples of individuals with CTE were procured and stained for SAP. In vitro assays that can measure the formation of fibrils and microglial/inflammation phenotype activation along with a repetitive mouse TBI (rmTBI) model were also conducted. Staining was evident for SAP in the brain samples for patients with CTE, which was not the case for the control patients. Inflammation markers were witnessed when SAP was present, and in the absence of SAP, anti-inflammatory markers were present. This supports the idea that SAP can control the inflammatory state of microglial cells. The results yielded that tau was induced in rmTBI and increased in mice with hSAP. It was also noted that anti-SAP antibodies reduced the hTau levels in the mice. This is indicative of the role that SAP has in the pathogenesis of CTE. The results can further lead to the development of therapeutic treatments for CTE and its pathogenesis through the understanding of the mechanism of SAP in the brain in regards to CTE.

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