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Dietary salt promotes cognitive impairment through tau phosphorylation
Faraco G, Hochrainer K, Segarra SG, Schaeffer S, Santisteban MM, Menon A, Jiang H, Holtzman DM et al.. Nature, 2019-10-23
Topic: Brain proteins, microglia and lab models
Dietary habits and vascular risk factors promote both Alzheimer's disease and cognitive impairment caused by vascular factors 1-3 . Furthermore, accumulation of hyperphosphorylated tau, a microtubule-associated protein and a hallmark of Alzheimer's pathology 4 , is also linked to vascular cognitive impairment 5,6 . In mice, a salt-rich diet leads to cognitive dysfunction associated with a nitric oxide deficit in cerebral endothelial cells and cerebral hypoperfusion 7 . Here we report that dietary salt induces hyperphosphorylation of tau followed by cognitive dysfunction in mice, and that these effects are prevented by restoring endothelial nitric oxide production. The nitric oxide deficiency reduces neuronal calpain nitrosylation and results in enzyme activation, which, in turn, leads to tau phosphorylation by activating cyclin-dependent kinase 5. Salt-induced cognitive impairment is not observed in tau-null mice or in mice treated with anti-tau antibodies, despite persistent cerebral hypoperfusion and neurovascular dysfunction. These findings identify a causal link between dietary salt, endothelial dysfunction and tau pathology, independent of haemodynamic insufficiency. Avoidance of excessive salt intake and maintenance of vascular health may help to stave off the vascular and neurodegenerative pathologies that underlie dementia in the elderly.
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APA 7th
Faraco, G., Hochrainer, K., Segarra, S. G., Schaeffer, S., Santisteban, M. M., Menon, A., et al. (2019). Dietary salt promotes cognitive impairment through tau phosphorylation. Nature. https://doi.org/10.1038/s41586-019-1688-z
Vancouver
Faraco G, Hochrainer K, Segarra SG, Schaeffer S, Santisteban MM, Menon A, et al. Dietary salt promotes cognitive impairment through tau phosphorylation. Nature. 2019. doi:10.1038/s41586-019-1688-z. PMID: 31645758.
BibTeX
@article{faraco2019-31645758,
author = {Faraco, G. and Hochrainer, K. and Segarra, S. G. and Schaeffer, S. and Santisteban, M. M. and Menon, A. and Jiang, H. and Holtzman, D. M. and others},
title = {{Dietary salt promotes cognitive impairment through tau phosphorylation}},
journal = {Nature},
year = {2019},
doi = {10.1038/s41586-019-1688-z},
pmid = {31645758},
url = {https://doi.org/10.1038/s41586-019-1688-z}
}
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Key findings
- In mice, a salt-rich diet leads to cognitive dysfunction associated with a nitric oxide deficit in cerebral endothelial cells and cerebral hypoperfusion 7 .
- The nitric oxide deficiency reduces neuronal calpain nitrosylation and results in enzyme activation, which, in turn, leads to tau phosphorylation by activating cyclin-dependent kinase 5.
- These findings identify a causal link between dietary salt, endothelial dysfunction and tau pathology, independent of haemodynamic insufficiency.
Why it matters
In mice, a salt-rich diet induced tau phosphorylation and cognitive dysfunction, and these effects were prevented by restoring endothelial nitric oxide production or by using anti-tau antibodies. This is animal research and does not yet show that reducing salt intake prevents dementia in humans.
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Study details
- Evidence strengthLow
How this study scored 54/100
Published in a top-tier journal. Scored zero for study design, sample size, effect reported, studied in people and randomised / blinded because the record does not state it.
| Component | Points | Why |
|---|---|---|
| Journal tier | 10 / 10 | Tier 1 — top-tier general journal (Nature) |
| Journal's citation record | 4 / 4 | Nature: journal h-index 1,841 (OpenAlex, 2026-10-29) |
| Study design | 0 / 12 | No study design recorded — scores zero, not guessed (not stated in the record — scored 0) |
| Strength of evidence | 1 / 5 | Rated “low” in our summary |
| Peer-review validation | 10 / 10 | Peer-reviewed. Published as an article in a named peer-reviewed journal. |
| How recent | 2 / 5 | 2019 — within 10 year(s) of the newest study here |
| Sample size | 0 / 4 | Participant count not stated — scores zero (not stated in the record — scored 0) |
| Effect reported | 0 / 3 | No effect size reported — scores zero (not stated in the record — scored 0) |
| Studied in people | 0 / 3 | Not stated whether this was studied in people — scores zero (not stated in the record — scored 0) |
| Randomised / blinded | 0 / 2 | No randomisation or blinding stated — scores zero (not stated in the record — scored 0) |
| Times cited | 5 / 7 | Cited 234 times (OpenAlex, 2026-10-10) |
| Citations per year | 4 / 5 | 26.0 citations a year over 9 year(s) since 2019 |
| Impact for its field and year | 4 / 6 | Cited 14.6× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 2 / 6 | Cited by 4 other studies in this library |
| Still being cited | 3 / 4 | Cited 103 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 4 / 4 | Last-listed author Costantino Iadecola: h-index 128 (OpenAlex, whole career) |
| Institution's track record | 2 / 3 | Washington University in St. Louis: institution h-index 1,962 (OpenAlex) |
| Multi-centre collaboration | 1 / 3 | OpenAlex lists 3 institution(s) in 1 country |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 31645758) |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Total | 54 / 100 | — |
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Read the original
- DOI: 10.1038/s41586-019-1688-z
- PubMed: 31645758
- Original source →
- Free full text: bioRxiv (Cold Spring Harbor Laboratory) →
Full text: free to read — OpenAlex lists this copy as free to read: the link above (checked 6 Feb 1020).
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