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Alzheimer’s disease (AD) is a neurodegenerative disorder characterized by progressive memory loss and neuropathological hallmarks of amyloid-β (Aβ) plaques and neurofibrillary tangles, with aging as a major risk factor. The amyloid cascade hypothesis proposes a causative role of Aβ in the disease development and has dominated the AD field for over 20 years. Recently this hypothesis has been increasingly challenged: Is Aβ the primary cause for the 95% of sporadic late-onset AD cases, or is it secondary to some other process? It has been proposed that cerebrovascular endothelial dysfunction during advanced aging, together with other risk factors, triggers the neurodegenerative processes in AD. L-arginine is a semi-essential amino acid with a number of bioactive metabolites. The gaseous signalling molecule nitric oxide (NO) derived from endothelial NO synthase (eNOS) plays a critical role in maintaining normal cerebral blood flow (CBF). In AD brains, there are dramatically reduced eNOS protein expression and altered arginine metabolic profile, and the plaques and tangles are associated with reduced capillary expression of eNOS. Interestingly, mice with complete eNOS deficiency display amyloidogenic processing of amyloid precursor protein, increased Aβ levels and tau phosphorylation in the brain, and memory deficits. This thesis aimed to further explore the implication of eNOS dysfunction for AD by investigating the effects of complete and partial eNOS deficiency on CBF, neurovascular coupling (NVC), L-arginine metabolism and its inter-related urea cycle. Experiment 1 systematically investigated how behavioural function, basal …