백석예술대학교 도서관

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Unraveling the Molecular and Physiological Mechanisms Leading to Vascular Dysfunction in Alzheimer's Disease- [electronic resource]

서명/저자: Unraveling the Molecular and Physiological Mechanisms Leading to Vascular Dysfunction in Alzheimers Disease - [electronic resource]

주기사항: Source: Dissertations Abstracts International, Volume: 84-12, Section: B.

초록/해제: 요약Alzheimer's disease (AD) is the most common form of dementia, characterized by the abnormal aggregation of amyloid beta and phosphorylated tau proteins in neurons and brain tissue. The causes of this disease are unknown, and there is currently no cure or effective treatment.Cerebral blood flow (CBF) is decreased by ~30% in both patients and animal models of Alzheimer's disease (AD), it's one of the earliest biomarkers and even precedes the appearance of amyloid plaques. Despite its significance in the disease progression, the underlying molecular and cellular mechanisms leading to CBF are not well understood. In this work, we explored the molecular and cellular mechanisms leading to CBF decrease in AD, by using advanced optical tools such as multiphoton microscopy, and genomics techniques that allow for the study of gene expression in cells, such as RNA sequencing.In the first section of this dissertation, using these techniques we show that vascular oxidative stress contributes significantly to CBF deficits, inflammation, and cognitive impairment in a mouse model of AD. In the second section, we explore the role of leukocytes in the microcirculation and how their slowed motion through capillaries alters the CBF dynamics locally in the vascular network. Finally, in the last section of this dissertation, we show how similar cellular mechanisms contribute to CBF deficits in a mouse model of sickle cell disease.