Neurovascular coupling (NVC), the tight coupling between neural activity and cerebral blood flow (CBF), is essential for brain function and integrity. Decreased CBF and altered NVC are among the earliest biomarkers of Alzheimer’s disease (AD) and may exacerbate its progression. Among the various cellular players of NVC, cyclooxygenase-2 (COX2) pyramidal cells, play a key role via the release of prostaglandin E2 (PGE2), which can bidirectionally control the NVC. We investigated the role of pyramidal cells in neurovascular uncoupling of AD using cortical slices from triple transgenic mice expressing channelrhodopsin-2 in pyramidal cells with or without the human APPIn,Swe variant at a presymptomatic stage of AD. The vascular response of diving arterioles to pharmacological applications or optogenetic stimulation was visualized by infrared videomicroscopy. Electrophysiological properties and the optogenetic stimulation of pyramidal cells were determined by patch-clamp recording. Both PGE2 (1 µM) and the thromboxane analogue, U46619 (100 nM), induced vasoconstriction in juvenile mice which was delayed and smaller in hAPP+ mice than in littermate controls. Pyramidal cells showed no difference in electrophysiological properties or optogenetic responses. However, 20 Hz photostimulation elicited vasoconstriction which tended to have slower kinetics in hAPP+ mice but not in controls. These preliminary results suggest that hAPP+ juvenile mice have an early impaired arteriolar vasoconstriction. Optogenetic observations suggest that these mice may also have modification in NVC early in life. Further experiments are required to confirm these changes, their progression and to determine the underlying mechanisms.