Functional imaging of the brain vasculature in pre-clinical models of amyloidosis

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 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. Netherlands Organization for Scientific Research (NWO) supported the research, under research program VIDI, project ‘Amyloid and Vessels’ (864.13.014); Alzheimer Nederland supported printing of the thesisLUMC / Geneeskund