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The anatomic distribution and expression of matricellular proteins in the cerebral vasculature of Alzheimer's Disease subjects

Lee, Grace (2018) The anatomic distribution and expression of matricellular proteins in the cerebral vasculature of Alzheimer's Disease subjects. Undergraduate Thesis, University of Pittsburgh. (Unpublished)

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Abstract

Alzheimer’s Disease (AD) is a progressive neurodegenerative disorder that is characterized by the deterioration of cognitive functioning. AD is the most common form of dementia amongst older adults and currently has no cure. Through extensive research that continues to be elucidated, there are two linked factors that may contribute to AD severity. The first is the presence of the epsilon 4 allele in the apolipoprotein E gene (ApoE4 allele), and the second is severity of cerebral amyloid angiopathy (CAA). In this project, gene expression of target genes TSP1, CD36, CD47, sirpα and hif-2α were investigated in relation to ApoE allele status and the degree of cerebral amyloid angiopathy in AD patients. Immunofluorescence and immunostaining procedures were carried out on post-mortem human brain tissue samples to detect target gene expression. The experimental cohort was made up of 20 subjects with Alzheimer’s disease pathology, while the non-diseased control cohort consisted of 6 subjects with minimal-to-no Alzheimer’s disease pathology. Immunostaining was followed by microscopy imaging and subsequent fluorescent quantification using Image J software (NIH). Standard statistical analyses were carried out on the results using the patient demographics of each cohort. ApoE allele status and CAA grade for each cohort were obtained after immunostaining and fluorescence quantification occurred, resulting in a blinded study to prevent bias. The results of this project concluded that TSP1, sirpα, and CD36 correlate with increasing CAA grade, while sirpα, CD36 and CD47 show a correlation with ApoE allele status. When looking at ApoE4 allele and CAA grade, TSP1, sirpα, and CD36 show a correlation to both factors, suggesting ApoE4 may cause increased CAA, which may result in more severe AD. Various signaling pathways through interactions between these target genes may contribute to severity of Alzheimer’s Disease. Further research will need to be done in order to examine these mechanisms.


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Details

Item Type: University of Pittsburgh ETD
Status: Unpublished
Creators/Authors:
CreatorsEmailPitt UsernameORCID
Lee, Gracegyl2@pitt.edugyl2
ETD Committee:
TitleMemberEmail AddressPitt UsernameORCID
Thesis AdvisorStraub, Adamastraub@pitt.edu
Committee MemberShiva, Srutisss43@pitt.edu
Committee MemberNovelli, Enriconoveex@upmc.edu
Committee MemberMcDade, Ericericmcdade@wustl.edu
Date: 26 April 2018
Date Type: Publication
Defense Date: 12 April 2018
Approval Date: 26 April 2018
Submission Date: 19 April 2018
Access Restriction: No restriction; Release the ETD for access worldwide immediately.
Number of Pages: 36
Institution: University of Pittsburgh
Schools and Programs: University Honors College
Dietrich School of Arts and Sciences > Biological Sciences
Degree: BPhil - Bachelor of Philosophy
Thesis Type: Undergraduate Thesis
Refereed: Yes
Uncontrolled Keywords: TSP1, CD47, CD36, Sirpα, Hif2-α, Alzheimer's Disease, cerebral amyloid angiopathy, ApoE4, neurodegenerative
Date Deposited: 26 Apr 2018 17:08
Last Modified: 26 Apr 2018 17:08
URI: http://d-scholarship.pitt.edu/id/eprint/34338

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  • The anatomic distribution and expression of matricellular proteins in the cerebral vasculature of Alzheimer's Disease subjects. (deposited 26 Apr 2018 17:08) [Currently Displayed]

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