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Background: Cerebral ionic homeostasis impairment, especially Ca2+, has been observed in Alzheimer's disease (AD) and also with hypertension. Hypertension and AD both have been implicated in impaired cerebral autoregulation. However, the relationship between the ionic homeostasis impairment inADand hypertension and cerebral blood flow(CBF) autoregulation is not clear. Objective: To test the hypothesis that a high-salt diet regimen influences the accumulation of amyloid-β (Aβ) and CBF, exacerbates cognitive decline, and increases the propensity to AD. Methods: Double transgenic mice harboring the amyloid-β protein precursor (APPswe), and presenilin-1 (PSEN1) along with control littermates, 2 months of age at initiation of special diet, were divided into 4 groups: Group A, APP/PS1 and Group B, controls fed a high-sodium (4.00%) chow diet for 3 months; Group C, APP/PS1 and Group D, controls fed a low-sodium (0.08%) regular chow diet for 3 months. Mean arterial blood pressure (MAP) and CBF were measured noninvasively using the tail MAP measurement device and magnetic resonance imaging, respectively. Aβ plaques numbers in the cortex and hippocampus of APP/PS1 were quantified. Results: In contrary to controls, APP/PS1 mice fed a high-salt diet did not showmarkedly elevated mean systolic and diastolic blood pressure (134±4.8 compared with 162±2.8 mmHg, and 114±5.0 compared with 137±20 mmHg, p < 0.0001). However, a high-salt diet increased CBF in both APP/PS1 and controls and did not alter the cerebral tissue integrity. Aβ plaques were significantly reduced in the cortex and hippocampus of mice fed a high-salt diet. Conclusion: These data suggest that a high-salt diet differently affects MAP and CBF in APP/PS1 mice and controls. [ABSTRACT FROM AUTHOR]