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

Authors

Sung-Ji Ahn, Benjamin Goya, Christian Bertomo, Rose Sciortino, Gianfranco Racchumi, Lidia Garcia Bonilla, Josef Anrather, Costantino Iadecola, Giuseppe Faraco

Published in

Cardiovascular research. Volume 121. Issue 16. Pages 2578-2593. Dec 18, 2025.

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, a 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 been linked to cognitive impairment in models of Alzheimer's disease and diabetes. Therefore, we tested the hypothesis that capillary stalling also contributes to CBF reduction, tau accumulation, and cognitive impairment in HSD.
We used in vivo two-photon imaging to assess capillary stalling in C57BL6/J male mice fed a normal diet or HSD. We found that HSD increased stalling of neutrophils in brain capillaries and decreased CBF. Neutrophil depletion using anti-Ly6G antibodies reduced the number of stalled capillaries and restored CBF, measured by red blood cell speed. Despite the improved CBF, chronic neutrophil depletion did not rescue HSD-induced cognitive impairment, assessed by the Barnes maze and nest building behavior. Furthermore, levels of phosphorylated tau in the cortex and hippocampus remained elevated in HSD mice after neutrophil depletion.
These novel findings show that capillary stalling contributes 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.

PMID:
41208407
Bibliographic data and abstract were imported from PubMed on 15 Sep 2026.

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