Neutrophil stalling does not mediate the increase in tau phosphorylation and the cognitive impairment associated with high salt diet

Abstract

High dietary salt intake has powerful effects on cerebral blood vessels and has emerged as a risk factor for stroke and cognitive impairment. In mice, high salt diet (HSD) leads to reduced cerebral blood flow (CBF), tau hyperphosphorylation and cognitive dysfunction. However, it is still unclear whether the reduced CBF is responsible for the effects of HSD on tau and cognition. Capillary stalling has emerged as a cause of CBF reduction and cognitive impairment in models of Alzheimers disease and diabetes. Therefore, we tested the hypothesis that capillary stalling also contributes to the CBF reduction and cognitive impairment in HSD. Using two-photon imaging, we found that HSD increased stalling of neutrophils in brain capillaries and decreased CBF. Neutrophil depletion reduced the number of stalled capillaries and restored resting CBF but did not prevent tau phosphorylation or cognitive impairment. These novel findings show that, capillary stalling contribute to CBF reduction in HSD, but not to tau phosphorylation and cognitive deficits. Therefore, the hypoperfusion caused by capillary stalling is not the main driver of the tau phosphorylation and cognitive impairment.