Introduction: Age-related dementia, or Alzheimer’s disease (AD), is the most common dementia, characterised by diffuse cerebral degeneration and cognitive decline. Hypertension is a strong risk factor for AD, and growing evidence indicates that the dementia results from pulse-induced haemorrhages in the cerebral microvasculature, and that plaques form as a result of those haemorrhages
Objectives: To test this microvascular haemorrhage hypothesis of AD we have assessed whether hypertension in a mouse model accelerates small-vessel haemorrhage, plaque pathology and cognitive loss, thus mimicking the human experience.
Methods: Hypertension was induced in APP/PS1 mice by constriction of the transverse aorta, at 3 mo. At 6mo, cognitive function was assessed by an automated IntelliCage system (NewBehavior, TSE Systems), arterial and ventricular pressures were recorded and brains were harvested for histopathology.
Results: Transverse aortic constriction (TAC) induced hypertension (144 ± 4/87 ± 4 mmHg, n=9 verses110 ± 2/79 ± 2 mmHg, n=15, in a control group P<0.01), a significant delay in learning in IntelliCage tasks, and a significant increase in Ab+ plaque formation in grey (neocortex, hippocampus, striatum, thalamus) and white matter (corpus callosum). In both normotensive and hypertensive brains, Ab+ plaques colocalised with haem deposits characterised by the Perls reaction, confirming the importance of haemorrhage in both cognitive loss and plaque pathology
Conclusions: Hypertension impairs cognitive function and accelerates Ab pathology in the transgenic APP/PS1 mouse, by accelerating the rate of haemorrhage from small vessels. This may represent how hypertension advances the onset of the corresponding dementia – Alzheimer’s disease - in humans.