Faraco G, Hochrainer K, Segarra SG, Schaeffer S, Santisteban MM, Menon A, Jiang H, Holtzman DM, Anrather J, Iadecola C. Dietary salt promotes cognitive impairment through tau phosphorylation. Nature. 2019 Oct;574(7780):686-690. Epub 2019 Oct 23 PubMed.

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  1. High-salt diets have long been associated with increased risk for dementia. However, the underlying mechanisms have largely been unknown. Faraco and colleagues (Faraco et al., 2018) recently presented an intriguing mechanism in mice, showing that a high-salt diet alters the gut biome, increasing circulating IL-17, which impairs endothelial function leading to reduced cerebral blood flow. From this it is reasonable to postulate that reduced cerebral blood flow is the primary driver of cognitive impairments associated with high-salt diet.

    However, Faraco and colleagues now expand upon this fascinating mechanism showing a high-salt diet can induce cognitive impairments independent of reduced cerebral blood flow. Instead, they demonstrate that a high-salt diet reduces endothelial nitric oxide, which activates neuronal Cdk5 and leads to hyperphosphorylation of tau and cognitive impairments. In humans, it remains unclear whether a high-salt diet contributes to age-related cognitive decline. However, these observations and mechanisms from mice will clearly help elucidate that relationship. Furthermore, Faraco and colleagues highlight that the importance of the brain’s microvasculature extends beyond regulating cerebral blood. They illustrate that neuronal cells and the cerebrovasculature have dynamic molecular and biochemical interactions that clearly influence neurodegenerative pathologies. Further unraveling these mechanisms will undoubtedly be a promising endeavor that will strengthen our understanding of how dietary habits influence susceptibility to age-related cognitive decline.

    References:

    Faraco G, Brea D, Garcia-Bonilla L, Wang G, Racchumi G, Chang H, Buendia I, Santisteban MM, Segarra SG, Koizumi K, Sugiyama Y, Murphy M, Voss H, Anrather J, Iadecola C. Dietary salt promotes neurovascular and cognitive dysfunction through a gut-initiated TH17 response. Nat Neurosci. 2018 Feb;21(2):240-249. Epub 2018 Jan 15 PubMed.

    View all comments by Joel Blanchard

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  1. Not Just Blood Pressure—Dietary Salt Linked to Tau Phosphorylation