Biomedical Sciences ETDs

Publication Date

Fall 12-12-2020

Abstract

Tauopathies are neurodegenerative diseases, including Alzheimer’s disease, that are associated with pathological accumulation of the microtubule associated protein tau (MAPT, or tau) (Lee et al., 2001). Abnormal hyperphosphorylated tau (pTau) strongly correlate with cognitive impairment (Nelson et al., 2012). Neuroinflammation is also associated with tauopathies (Gerhard et al., 2006b; Edison et al., 2008) and is implicated in driving tau pathology (Yoshiyama et al., 2007, Maphis et al., 2015b). Therefore, it is compelling to understand the role of anti-inflammatory cytokines in limiting neuroinflammation and tau pathology. Interleukin-10 (IL-10) is a well-established anti-inflammatory cytokine with roles in limiting inflammation in the central nervous system (CNS) (Strle et al., 2001; Lobo-Silva et al., 2016; Burmeister and Marriott, 2018). Here, we determine if IL-10 regulates inflammation-induced tau pathology by examining the role of IL-10 on tau phosphorylation during an acute inflammatory challenge. We also examined IL-10 in the context of slow progression of neuroinflammation and pTau progression in an hTau mouse model. Our findings suggest a distinct importance of IL-10 in limiting tau hyperphosphorylation after an acute inflammatory challenge, however, its role in limiting early expression and/or chronic progression of cytokines and tau phosphorylation remains unclear.

Keywords

Alzheimer's, Anti-inflammatory, Interleukin-10, Microglia, Neuroinflammation, Tau

Document Type

Dissertation

Language

English

Degree Name

Biomedical Sciences

Level of Degree

Doctoral

Department Name

Biomedical Sciences Graduate Program

First Committee Member (Chair)

Dr. Kiran Bhaskar

Second Committee Member

Dr. Bryce Chackerian

Third Committee Member

Dr. Erin Milligan

Fourth Committee Member

Dr. Eliseo Castillo

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