Evidence of cortical vascular impairments in early stage of Alzheimer’s transgenic mice: Optical imaging

Alzheimer's disease (AD), a neurodegenerative disorder with progressive cognitive decline, remains clinically challenging with limited understanding of etiology and interventions. Clinical studies have reported vascular defects prior to other pathological manifestations of AD, leading to the "Vascular Hypothesis" for the disorder. However, <i>in vivo</i> assessments of cerebral vasculature in AD rodent models have been constrained by limited spatiotemporal resolution or field of view of conventional imaging. We herein employed two <i>in vivo</i> imaging technologies, Dual-Wavelength Imaging and Optical Coherence Doppler Tomography, to evaluate cerebrovascular reactivity (CVR) to vasoconstrictive cocaine and vasodilatory hypercapnia challenges and to detect resting 3D cerebral blood flow (CBF) in living transgenic AD mice at capillary resolution. Results showed that CVR to cocaine and hypercapnia was significantly attenuated in 7-10 months old AD mice vs controls, indicating reduced vascular flexibility and reactivity. Additionally, in the AD mice, arterial CBF velocities were slower and the microvascular density in cortex was decreased compared to controls. These results reveal significant vascular impairments including reduced CVR and resting CBF in early-staged AD mice. Hence, this cutting-edge <i>in vivo</i> optical imaging offers an innovative venue for detecting early neurovascular dysfunction in AD brain with translational potential.