Assessment of neurovascular coupling and cortical spreading depression in mixed mouse models of atherosclerosis and Alzheimer's disease

Neurovascular coupling is a critical brain mechanism whereby changes to blood flow accompany localised neural activity. The breakdown of neurovascular coupling is linked to the development and progression of several neurological conditions including dementia. In this study, we examined cortical haemodynamics in mouse preparations that modelled Alzheimer's disease (J20-AD) and atherosclerosis (PCSK9-ATH) between 9 and 12 m of age. We report novel findings with atherosclerosis where neurovascular decline is characterised by significantly reduced blood volume, altered levels of oxyhaemoglobin and deoxyhaemoglobin, in addition to global neuroinflammation. In the comorbid mixed model (J20-PCSK9-MIX), we report a 3 x increase in hippocampal amyloid-beta plaques. A key finding was that cortical spreading depression (CSD) due to electrode insertion into the brain was worse in the diseased animals and led to a prolonged period of hypoxia. These findings suggest that systemic atherosclerosis can be detrimental to neurovascular health and that having cardiovascular comorbidities can exacerbate pre-existing Alzheimer's-related amyloid-plaques.

Automated summary

Neurovascular coupling is key for brain health, but its disruption is linked to neurological diseases like dementia. This study examines cortical haemodynamics in mouse models of Alzheimer's disease and atherosclerosis, finding reduced blood volume, altered haemoglobin levels, and neuroinflammation in atherosclerosis, as well as increased amyloid-beta plaques in the hippocampus. Importantly, electrode insertion worsens cortical spreading depression and leads to prolonged hypoxia in diseased animals. Atherosclerosis can negatively affect neurovascular health, and cardiovascular comorbidities can worsen Alzheimer's-related plaques.