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IDENTIFICATION OF NOVEL TARGETS FOR PSYCHOSIS IN AD WITH REAL WORLD EVIDENCE AND NETWORK ANALYSIS APPROACHES

Peihao, Fan (2019) IDENTIFICATION OF NOVEL TARGETS FOR PSYCHOSIS IN AD WITH REAL WORLD EVIDENCE AND NETWORK ANALYSIS APPROACHES. Master's Thesis, University of Pittsburgh. (Unpublished)

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Abstract

Alzheimer’s disease (AD) is a chronic neurodegenerative disease frequently seen in the aging process and causes significant loss of life quality and financial costs. Psychotic disorder also termed as psychosis, marked by failure to differentiate illusions from reality, is a major complication of AD (AD+P). About 50% of AD patients will develop psychotic symptoms including hallucinations and delusions. Therefore, a better understanding of the connection between AD and psychosis at the molecular level is urgently needed. Novel drug targets are critical in delaying the development of psychosis in AD. In this study, Real-World Evidence (RWE) data-mining and Network analysis approaches are combined to provide an inner view of the connection between AD and psychosis and help identify novel drug targets. Statistical analysis is performed on data of medication usage from the electronic medical records of AD patients with or without psychosis symptoms (AD+P vs. AD-P), survival analysis is also conducted on time to psychosis. Results showed that Vitamin D was significantly associated with delayed time to psychosis and also used more in AD-P patients than in AD+P patients. The network analysis also identified some high-impact genes in the overlapping part of AD and psychosis, including NOTCH4, COMT, CACNA1C and DRD3 which are related to calcium homeostasis. The combined results suggest a connection between AD+P development and calcium homeostasis and may provide a new direction for drug development.


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Details

Item Type: University of Pittsburgh ETD
Status: Unpublished
Creators/Authors:
CreatorsEmailPitt UsernameORCID
Peihao, Fanpef14@pitt.edupef14
ETD Committee:
TitleMemberEmail AddressPitt UsernameORCID
Committee ChairJunmei, Wangjunmei.wang@pitt.edujunmei.wang
Committee MemberXiangqun, Xiexix15@pitt.eduxix15
Committee MemberRobert, SweetSweetRA@upmc.eduSweetRA
Committee MemberLirong, WangLIW30@pitt.eduLIW30
Date: 11 April 2019
Date Type: Publication
Defense Date: 2 April 2019
Approval Date: 11 April 2019
Submission Date: 10 April 2019
Access Restriction: 3 year -- Restrict access to University of Pittsburgh for a period of 3 years.
Number of Pages: 95
Institution: University of Pittsburgh
Schools and Programs: School of Pharmacy > Pharmaceutical Sciences
Degree: MS - Master of Science
Thesis Type: Master's Thesis
Refereed: Yes
Uncontrolled Keywords: Alzheimer’s Disease; Psychosis; Vitamin D; Calcium Homeostasis; Systems Pharmacology; Real-World Evidence
Date Deposited: 11 Apr 2019 15:20
Last Modified: 11 Apr 2019 15:20
URI: http://d-scholarship.pitt.edu/id/eprint/36379

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