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Potential Blood Biological Markers of Alzheimer's Disease

Metti, Andrea (2013) Potential Blood Biological Markers of Alzheimer's Disease. Doctoral Dissertation, University of Pittsburgh. (Unpublished)

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Abstract

Alzheimer’s disease (AD) affects millions of older adults worldwide, and the prevalence and incidence are expected to grow at exponential rates in coming years. Identifying potential targets for intervention to delay onset, slow progression, or effectively treat AD is of extreme public health importance. Better understanding blood biomarkers of AD is one means of identifying such targets. This dissertation investigates potential blood biomarkers of AD, including plasma amyloid beta 42 (Aβ42) and Aβ40, and inflammatory markers interleukin 6 (IL-6), IL-6 soluble receptor (IL-6 sR), and C-reactive protein (CRP).

Measurement of Aβ42 and Aβ40 in cerebrospinal fluid has been used to identify people with AD, and distinguish from other types of dementia. In plasma, the ratio Aβ42/Aβ40 has emerged as a potentially useful biomarker of AD. However, correlates of plasma Aβ40 and Aβ42 are unknown. We investigated the demographic and medical correlates of plasma Aβ40 and Aβ42. We found that in community-dwelling, older adults, plasma Aβ40 and Aβ42 were significantly associated with age, race, sex, education, Apolipoprotein E (APOE) genotype, and serum creatinine.

Due to the inflammatory state associated with AD pathology, and with risk factors of AD, inflammatory markers are potentially useful biomarkers of AD. Previous studies have focused on measuring inflammatory markers at one time point; this has major limitations due to the non-specific nature of inflammatory markers, and the large number of inflammation triggers. We studied how change in inflammation over time predicts risk of dementia and cognitive decline. In a cohort of oldest old women, we found that high IL-6 sR at two time points, or transitioning to from low to high reduced the risk of developing dementia. Furthermore, in a cohort of older, black and white men and women, we found that extreme variability in CRP over time was associated with increased risk for cognitive decline over 10 years. This association was stronger among women and among those with no APOE e4 allele. We believe these results not only indicate the complexity of the immune system in older adults, but also suggest the role of vascular disease in the development of cognitive decline. New evidence suggesting that vascular disease is also related to Aβ deposition suggests that the relationships we found may hold for vascular dementia and AD. Future research should investigate how all of these markers together relate to cognitive function, as well as to AD and vascular dementia pathologies, such as amyloid deposition and white matter hyperintensities.


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Details

Item Type: University of Pittsburgh ETD
Status: Unpublished
Creators/Authors:
CreatorsEmailPitt UsernameORCID
Metti, Andreaalw111@pitt.eduALW111
ETD Committee:
TitleMemberEmail AddressPitt UsernameORCID
Committee ChairCauley, JaneJCauley@edc.pitt.eduJCAULEY
Committee MemberBoudreau, RobertBoudreauR@edc.pitt.eduROB21
Committee MemberGanguli, Marygangulim@msx.upmc.edu
Committee MemberLopez, Oscarlopezol@upmc.eduOLLOPEZ
Committee MemberRosano, Caterinarosanoc@edc.pitt.eduCAR2350
Committee MemberYaffe, Kristinekristine.yaffe@ucsf.edu
Date: 27 June 2013
Date Type: Publication
Defense Date: 28 March 2013
Approval Date: 27 June 2013
Submission Date: 14 March 2013
Access Restriction: 3 year -- Restrict access to University of Pittsburgh for a period of 3 years.
Number of Pages: 165
Institution: University of Pittsburgh
Schools and Programs: Graduate School of Public Health > Epidemiology
Degree: PhD - Doctor of Philosophy
Thesis Type: Doctoral Dissertation
Refereed: Yes
Uncontrolled Keywords: Alzheimer's disease, inflammation, amyloid beta, biological markers
Date Deposited: 27 Jun 2013 18:33
Last Modified: 19 Dec 2016 14:40
URI: http://d-scholarship.pitt.edu/id/eprint/17749

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