One of the pathological hallmarks of Alzheimer's disease is amyloid‑β accumulation in the parenchymal brain tissue. Amyloid‑β is also found in the vessel wall of patients with cerebral amyloid... Show moreOne of the pathological hallmarks of Alzheimer's disease is amyloid‑β accumulation in the parenchymal brain tissue. Amyloid‑β is also found in the vessel wall of patients with cerebral amyloid angiopathy (CAA). These pathological accumulations of the amyloid‑β peptide are referred to as amyloidosis. Both patients with AD and CAA also commonly show cerebrovascular dysfunction. The aim of this thesis was to improve our understanding of the relation between cerebrovascular dysfunction and amyloidosis. To that end, cerebrovascular function measurements were designed and carried out in mouse models of cerebral amyloidosis. Chapter 2 and 3 show improvements of the current techniques to measure cerebrovascular function in mice. Surprisingly however, no difference was found in cerebrovascular function in two different models of amyloidosis, as shown in chapter 4 and 5. Possible explanations of the negative findings are further discussed in chapter 6. Despite the negative connotation of the outcome this thesis, this work is another small step towards a better understanding of the exact relationship between cerebrovascular dysfunction and amyloid‑β deposition in AD and CAA patients. Ultimately, this will help in the design of highly needed novel therapies for AD and CAA. Show less
Nho, K.; Kueider-Paisley, A.; Mahmoudian Dekhordi, S.; Arnold, M.; Risacher, S.L.; Louie, G.; ... ; Kaddurah-Daouk, R. 2018
Alzheimer__s disease (AD) is the predominant form of dementia in the aging population and its increasing incidence represents an important socio-economic and public health concern. The hallmarks of... Show moreAlzheimer__s disease (AD) is the predominant form of dementia in the aging population and its increasing incidence represents an important socio-economic and public health concern. The hallmarks of this disease, amyloid plaques and neurofibrillary tangles, are thought to develop early in the disease pathogenesis, up to decades before first clinical symptoms occur. However, these pathological hallmarks are still difficult to detect in vivo, and therefore a definitive diagnosis can only be made post-mortem. A clinical imaging technique or biomarker capable of visualizing and quantifying amyloid plaques and associated early changes thus may enable an earlier diagnosis, better understanding of the pathophysiology and eventually aid therapy development. The work presented in this thesis aimed to develop innovative diagnostic imaging techniques to detect the histological signatures of AD using emerging ultra-high field MRI technologies (Part I) and molecular imaging strategies (Part II). Show less
