Cerebral Aβ40 and systemic hypertension

Abstract

Mid-life hypertension and cerebral hypoperfusion may be preclinical abnormalities in people who later develop Alzheimer’s disease. Although accumulation of amyloid-beta (Aβ) is characteristic of Alzheimer’s disease and is associated with upregulation of the vasoconstrictor peptide endothelin-1 within the brain, it is unclear how this affects systemic arterial pressure. We have investigated whether infusion of Aβ40 into ventricular cerebrospinal fluid modulates blood pressure in the Dahl salt-sensitive rat. The Dahl salt-sensitive rat develops hypertension if given a high-salt diet. Intracerebroventricular infusion of Aβ induced a progressive rise in blood pressure in rats with pre-existing hypertension produced by a high-salt diet (p < 0.0001), but no change in blood pressure in normotensive rats. The elevation in arterial pressure in high-salt rats was associated with an increase in low frequency spectral density in systolic blood pressure, suggesting autonomic imbalance, and reduced cardiac baroreflex gain. Our results demonstrate the potential for intracerebral Aβ to exacerbate hypertension, through modulation of autonomic activity. Present findings raise the possibility that mid-life hypertension in people who subsequently develop Alzheimer’s disease may in some cases be a physiological response to reduced cerebral perfusion complicating the accumulation of Aβ within the brain.