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The role of TREM2 in microglia function and Alzheimer's disease

Lu, Yi (2020) The role of TREM2 in microglia function and Alzheimer's disease. Master's Thesis, University of Pittsburgh. (Unpublished)

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Abstract

Alzheimer’s disease (AD) is the leading cause of dementia and death in the United States. AD is characterized by extracellular amyloid plaques and intracellular neurofibrillary tangles. Patients are classified into early-onset AD (EOAD), which are developed before 65, and late-onset AD (LOAD), developed after 65. Three causative genes were identified for EOAD: amyloid precursor protein (APP), presenilin (PSEN) 1 and 2. However, there are no causative genes found for LOAD. Risk factors of AD are complicated, including aging, family histories, high cholesterol levels, high blood pressure, brain injuries, and genetic risk factors. Recent genome-wide association studies have identified a set of genetic risk factors for LOAD, including the triggering receptor expressed on myeloid cells 2 (TREM2) and apolipoprotein E (APOE). Studies have identified several rare variants of TREM2 to increase the risk of developing LOAD by 2-4-fold. In the central nervous system (CNS), microglia play an important role in responding to plaque accumulation during AD pathology. TREM2, as the receptor of microglia, was proposed to affect microglia functions, including survival, proliferation, chemotaxis, and phagocytosis. TREM2 was also found to impair the activation of homeostatic microglia and energy metabolism of microglia cells. This review summarized previous studies in the past 5 years and elucidated the current understanding of the role of TREM2 in microglia function and AD pathology, as well as opportunities and challenges of targeting of TREM2 as a potential therapeutic strategy, which is of high public health significance.


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Details

Item Type: University of Pittsburgh ETD
Status: Unpublished
Creators/Authors:
CreatorsEmailPitt UsernameORCID
Lu, Yiyil197@pitt.eduyil197
ETD Committee:
TitleMemberEmail AddressPitt UsernameORCID
Barchowsky, Aaronaab20@pitt.edu
Thesis AdvisorKoldamova, Radaradak@pitt.edu
Iordanova, Bistrabei3@pitt.edu
Date: 30 July 2020
Date Type: Publication
Defense Date: 11 June 2019
Approval Date: 30 July 2020
Submission Date: 31 March 2020
Access Restriction: No restriction; Release the ETD for access worldwide immediately.
Number of Pages: 35
Institution: University of Pittsburgh
Schools and Programs: Graduate School of Public Health > Environmental and Occupational Health
Degree: MS - Master of Science
Thesis Type: Master's Thesis
Refereed: Yes
Uncontrolled Keywords: TREM2, Microglia, Alzheimer's Disease
Date Deposited: 31 Jul 2020 02:31
Last Modified: 31 Jul 2020 02:31
URI: http://d-scholarship.pitt.edu/id/eprint/38470

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