Investigating vasomotion and neurovascular function in pre-clinical models of Alzheimer’s disease & hypertension

Background: Vascular risk factors, particularly hypertension (HTN), are key contributors to the development of Alzheimer’s disease (AD). Both conditions are linked to cerebral vascular dysfunction, potentially disrupting processes such as vasomotion and neurovascular coupling (NVC). Vasomotion, a low-frequency (~0.1 Hz) oscillation in vascular diameter, is thought to support tissue oxygenation, perfusion, and solute clearance from the brain. NVC is a critical process for brain health, and its impairment is believed to play a central role in AD pathophysiology.

Aims: This project aimed to (I) characterise vasomotion in vivo and explore its potential as an early biomarker of vascular dysfunction in AD and HTN; (II) examine the relationship between vasomotion and neuronal activity; and (III) assess how HTN affects brain vascular function.

Methods: Low-frequency oscillations (LFOs; 0.06–0.2 Hz) in cerebral arteries of AD (J20-AD), HTN (angiotensin-II-induced), and healthy control mice were measured using 2D-optical imaging spectroscopy and compared between groups. Simultaneously gathered multi-unit neuronal activity data were used to assess whether LFOs were independent of neural activity. In HTN mice, neurovascular function, cognition, and cellular changes were also evaluated through in vivo imaging, electrophysiology, behavioural paradigms, and immunohistochemistry.

Results: LFO power was unchanged in AD mice but significantly reduced in male HTN mice versus controls. This reduction preceded detectable changes in NVC, cognition, and histology, suggesting LFO deficits as early indicators of HTN-related dysfunction. LFOs were also coupled to neuronal activity, providing important insights into the interpretation of vasomotion signals in-vivo. While NVC was largely preserved in HTN mice, a faster onset of haemodynamic responses were observed in HTN mice compared to controls, suggesting that temporal features of NVC may offer a more sensitive index of early vascular dysfunction. Sex significantly influenced both haemodynamic responses and LFOs, emphasising the importance of sex-aware approaches in neurovascular research.