The microcirculation of the brain is increasingly viewed as a potential target for disease modifying drugs in the treatment of the patient with Alzheimer’s Dementia (AD). However, despite established changes to cerebrovascular autoregulation in patients with AD, underlying pathogenic mechanisms in isolated brain resistance arteries have not been investigated. Here we present the first detailed examination of the principal vasodilatory pathways within small cerebral arteries in an AD mouse model. For our study we used the APP23 mouse which has a seven-fold increase in amyloid precursor protein leading to neuritic plaques and also cerebrovascular accumulation of amyoid-β, similarly to patients with AD. Using a range of physiological techniques; mainly pressure myography, patch clamp electrophysiology and high-speed spinning disc confocal microscopy, we show that a global vascular dysfunction within this model is underpinned by two distinct channelopathies. Firstly we showed an attenuation of large conductance Ca2+–activated K+ (BK) channel function as a decreased contractility to the BK channel blocker, paxilline (p = <0.001, unpaired t test, n = 8-12 arteries per group). Further investigation determined that the BK channels from the APP23 vascular smooth muscle cells produced significantly less spontaneous transient outward currents (p = <0.01, two way ANOVA, n = 10-14 cells per group) and that this was correlated to a significantly reduced frequency of calcium sparks (p = <0.05, unpaired t test, n = 5-7 arteries per group). Thus, the increase in myogenic tone from these animals (p = <0.01, unpaired t test, 25-29 arteries per group) was a result of a lack of calcium spark activation of the BK channel. This observation was accompanied by a reduction in the vasodilatory capacity of the endothelial inward rectifier K+ channel, Kir2.1 (p = <0.05, unpaired t test, 10-11 arteries per group), indicating a deficit in neurovascular coupling in these animals. If present in human AD, the combination of these pathologies would account for the clinical cerebrovascular presentation seen in patients: reduced blood flow and a failure of functional hyperaemia. The data directs future research to approaches that will reverse this dual vascular channelopathy, with the ultimate aim of restoring healthy cerebral blood flow and improving clinical outcomes.