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Effects of Peripheral Inflammation and Neuroinflammation on Clinical and Neuroimaging Outcomes Across the Alzheimer's Disease Spectrum
Effects of Peripheral Inflammation and Neuroinflammation on Clinical and Neuroimaging Outcomes Across the Alzheimer's Disease Spectrum
상세정보
- 자료유형
- 학위논문 서양
- 최종처리일시
- 20260202105644
- ISBN
- 9798270237646
- DDC
- 614.4
- 서명/저자
- Effects of Peripheral Inflammation and Neuroinflammation on Clinical and Neuroimaging Outcomes Across the Alzheimers Disease Spectrum
- 발행사항
- [Sl] : University of Pittsburgh, 2025
- 발행사항
- Ann Arbor : ProQuest Dissertations & Theses, 2025
- 형태사항
- 261 p
- 주기사항
- Source: Dissertations Abstracts International, Volume: 87-06, Section: B.
- 주기사항
- Advisor: Shaaban, C. Elizabeth.
- 학위논문주기
- Thesis (Ph.D.)--University of Pittsburgh, 2025.
- 초록/해제
- 요약Alzheimer Disease (AD) is a neurodegenerative disease characterized by the accumulation of amyloid-beta (Aβ) and tau. Neuroinflammation is also, a relevant feature of AD. Neuroinflammation, as measured by glial fibrillary acidic protein (GFAP) represents astrocyte cell activation (a.k.a astrogliosis) and is associated with greater AD pathology. Studies suggest that the interaction of astrogliosis with peripheral inflammation is associated with worse cognitive performance and greater AD pathology and that this interaction is different across brain regions. However, GFAP levels do not inform spatial localization; however, a new neuroimaging radiotracer (18F-SMBT-1) validated for astrogliosis in AD permits the examination of different brain regions.This dissertation aims to better understand the interplay of peripheral inflammation and astrogliosis, which until now have been addressed mainly from a theoretical point of view. The successful completion of these aims will overcome an important gap in the field. To achieve those aims, I collaborated with: the Ginkgo Evaluation Memory Study (GEMS) and the INflammation ROles in Aging and Alzheimer's disease Study (INROAADS) a large study on the role of astrogliosis in aging and AD. In my first paper, I found that markers of peripheral inflammation (CRP and TNFR1) in combination with astrogliosis associated with greater vascular burden, and more neurodegeneration. In my second paper, I found that there was a clinically relevant association of the combination of astrogliosis with peripheral inflammatory mediators (sIL2R, TNFR1) on time to progression to AD dementia and length of survival. In my third paper, I found that astrogliosis either measured as GFAP or 18F-SMBT-1 was associated with worse cognition (visuospatial function), particularly among participants with high Aβ (Aβ+). Further, an exploratory analysis showed that IGFR1 appears to suppress the detrimental effect of astrogliosis on cognition. Taken together, my findings suggest that, in combination, peripheral inflammation and astrogliosis may play a role in the pathophysiology of Alzheimer's disease. Furthermore, the exploratory findings on IGFR offer a new landscape for future assessment of how this growth factor may serve as potential target for intervention to promote resilience among individuals who had already developed Aβ pathology and to slow the progression of cognitive decline.
- 일반주제명
- Epidemiology
- 일반주제명
- Neurosciences
- 일반주제명
- Medical imaging
- 키워드
- Inflammation
- 키워드
- Neuroimaging
- 기타저자
- University of Pittsburgh Epidemiology
- 기본자료저록
- Dissertations Abstracts International. 87-06B.
- 전자적 위치 및 접속
- 로그인 후 원문을 볼 수 있습니다.
MARC
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■00520260202105644
■006m o d
■007cr#unu||||||||
■020 ▼a9798270237646
■035 ▼a(MiAaPQ)AAI32399545
■040 ▼aMiAaPQ▼cMiAaPQ
■0820 ▼a614.4
■1001 ▼aRamirez Tirado, Laura Alejandra.
■24510▼aEffects of Peripheral Inflammation and Neuroinflammation on Clinical and Neuroimaging Outcomes Across the Alzheimer's Disease Spectrum
■260 ▼a[Sl]▼bUniversity of Pittsburgh▼c2025
■260 1▼aAnn Arbor▼bProQuest Dissertations & Theses▼c2025
■300 ▼a261 p
■500 ▼aSource: Dissertations Abstracts International, Volume: 87-06, Section: B.
■500 ▼aAdvisor: Shaaban, C. Elizabeth.
■5021 ▼aThesis (Ph.D.)--University of Pittsburgh, 2025.
■520 ▼aAlzheimer Disease (AD) is a neurodegenerative disease characterized by the accumulation of amyloid-beta (Aβ) and tau. Neuroinflammation is also, a relevant feature of AD. Neuroinflammation, as measured by glial fibrillary acidic protein (GFAP) represents astrocyte cell activation (a.k.a astrogliosis) and is associated with greater AD pathology. Studies suggest that the interaction of astrogliosis with peripheral inflammation is associated with worse cognitive performance and greater AD pathology and that this interaction is different across brain regions. However, GFAP levels do not inform spatial localization; however, a new neuroimaging radiotracer (18F-SMBT-1) validated for astrogliosis in AD permits the examination of different brain regions.This dissertation aims to better understand the interplay of peripheral inflammation and astrogliosis, which until now have been addressed mainly from a theoretical point of view. The successful completion of these aims will overcome an important gap in the field. To achieve those aims, I collaborated with: the Ginkgo Evaluation Memory Study (GEMS) and the INflammation ROles in Aging and Alzheimer's disease Study (INROAADS) a large study on the role of astrogliosis in aging and AD. In my first paper, I found that markers of peripheral inflammation (CRP and TNFR1) in combination with astrogliosis associated with greater vascular burden, and more neurodegeneration. In my second paper, I found that there was a clinically relevant association of the combination of astrogliosis with peripheral inflammatory mediators (sIL2R, TNFR1) on time to progression to AD dementia and length of survival. In my third paper, I found that astrogliosis either measured as GFAP or 18F-SMBT-1 was associated with worse cognition (visuospatial function), particularly among participants with high Aβ (Aβ+). Further, an exploratory analysis showed that IGFR1 appears to suppress the detrimental effect of astrogliosis on cognition. Taken together, my findings suggest that, in combination, peripheral inflammation and astrogliosis may play a role in the pathophysiology of Alzheimer's disease. Furthermore, the exploratory findings on IGFR offer a new landscape for future assessment of how this growth factor may serve as potential target for intervention to promote resilience among individuals who had already developed Aβ pathology and to slow the progression of cognitive decline.
■590 ▼aSchool code: 0178.
■650 4▼aEpidemiology
■650 4▼aNeurosciences
■650 4▼aMedical imaging
■653 ▼aInflammation
■653 ▼aNeuroinflammation
■653 ▼aNeuroimaging
■653 ▼aAlzheimer Disease
■690 ▼a0766
■690 ▼a0574
■690 ▼a0317
■71020▼aUniversity of Pittsburgh▼bEpidemiology.
■7730 ▼tDissertations Abstracts International▼g87-06B.
■790 ▼a0178
■791 ▼aPh.D.
■792 ▼a2025
■793 ▼aEnglish
■85640▼uhttp://www.riss.kr/pdu/ddodLink.do?id=T17360957▼nKERIS▼z이 자료의 원문은 한국교육학술정보원에서 제공합니다.
