Date of Award

Winter 12-21-2022

Degree Type

Thesis

Degree Name

MS Microbiology

Department

Biology

Advisor

C.J. Urso, PhD

Committee Member

Chintha Ranasinghe, MD

Committee Member

Constantine Bitsaktsis, PhD

Committee Member

Jessica Cottrell, PhD

Keywords

Alzheimer’s Disease, Microglia, TREM2, DHA, fatty acids, Aβ plaques

Abstract

Alzheimer’s disease (AD) is a neurological disease that is associated with microglia activation. An important receptor involved in microglia activation is Triggering receptor expressed on myeloid cells 2 (TREM2). Recent studies suggest that docosahexaenoic acid (DHA) could reduce the neuroinflammation that is associated with microglia activation. We hypothesized that when DHA concentration was increased, TREM2 expression would decrease, microglia activity would be inhibited, and a resulting decrease in neuroinflammation would be observed. We examined peer-reviewed journal articles from 2017-2022 that investigated the relationship between TREM2 activation and severity of AD symptoms, the protective properties of DHA against AD, and the role of DHA concentration in modulating TREM2 expression. The data reviewed support our hypothesis that an increase in DHA would be associated with a decrease in TREM2 expression and biomarkers of neuroinflammation. Interestingly, other work suggests AD is associated with an increase in TREM2 expression leading to a corresponding decrease in DHA concentration. These studies suggest that this mechanism may play a role in the progression of AD. Our proposed studies seek to (1) investigate DHA-TREM2 binding dynamics, (2) the role of DHA on TREM2 signaling, and (3) examine how other fatty acids interact with TREM2 and its signaling pathway.

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