Department of Infection, Immunity and Cardiovascular Disease (IICD), University of Sheffield Medical School, Royal Hallamshire Hospital, Sheffield, United Kingdom; Healthy Lifespan Institute (HELSI), University of Sheffield, Sheffield, United Kingdom; Neuroscience Institute, University of Sheffield, Sheffield, United Kingdom
Ben Pendry
Sheffield Institute for Translational Neuroscience (SITraN), University of Sheffield, Sheffield, United Kingdom
Neuroscience Institute, University of Sheffield, Sheffield, United Kingdom; Sheffield Neurovascular Lab, Department of Psychology, University of Sheffield, Sheffield, United Kingdom
Beth Eyre
Neuroscience Institute, University of Sheffield, Sheffield, United Kingdom; Sheffield Neurovascular Lab, Department of Psychology, University of Sheffield, Sheffield, United Kingdom
Paul S Sharp
Medicines Discovery Catapult, Alderley Edge, United Kingdom
Monica A Rebollar
Neuroscience Institute, University of Sheffield, Sheffield, United Kingdom; Sheffield Institute for Translational Neuroscience (SITraN), University of Sheffield, Sheffield, United Kingdom
David Drew
Department of Infection, Immunity and Cardiovascular Disease (IICD), University of Sheffield Medical School, Royal Hallamshire Hospital, Sheffield, United Kingdom
Healthy Lifespan Institute (HELSI), University of Sheffield, Sheffield, United Kingdom; Neuroscience Institute, University of Sheffield, Sheffield, United Kingdom; Sheffield Neurovascular Lab, Department of Psychology, University of Sheffield, Sheffield, United Kingdom
Paul R Heath
Sheffield Institute for Translational Neuroscience (SITraN), University of Sheffield, Sheffield, United Kingdom
Stephen B Wharton
Neuroscience Institute, University of Sheffield, Sheffield, United Kingdom; Sheffield Institute for Translational Neuroscience (SITraN), University of Sheffield, Sheffield, United Kingdom
Sheila E Francis
Department of Infection, Immunity and Cardiovascular Disease (IICD), University of Sheffield Medical School, Royal Hallamshire Hospital, Sheffield, United Kingdom; Healthy Lifespan Institute (HELSI), University of Sheffield, Sheffield, United Kingdom; Neuroscience Institute, University of Sheffield, Sheffield, United Kingdom
Jason Berwick
Healthy Lifespan Institute (HELSI), University of Sheffield, Sheffield, United Kingdom; Neuroscience Institute, University of Sheffield, Sheffield, United Kingdom; Sheffield Neurovascular Lab, Department of Psychology, University of Sheffield, Sheffield, United Kingdom
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.
