Frontiers in Neurology · Oct 26, 2026
Dietary high salt drives cognitive impairment and Aβ accumulation via an insufficient compensatory mitophagy response
By Wen J, Ren H, Wen F et al.
There is mounting evidence that dietary habits are strongly correlated with cerebrovascular diseases and dementia, but the precise mechanism remains unclear how a salt-rich diet adversely affects the brain. Here, 12-month-old mice were fed a high-salt diet (HSD) for 2 months, and we observed salt-induced cognitive deficits in mice. The short-term HSD increased mitophagy-associated markers (PINK1, Parkin, and LC3-II) and decreased SQSTM1/p62, consistent with a compensatory mitophagy response that was insufficient to prevent cognitive decline. Neuro-2a cells were cultured in normal medium, NaCl medium (40 mM) or NaCl (40 mM) + CCCP group (20 μM) medium for 24 h, respectively. Short-term HSD feeding impaired learning and memory and increased amyloid-β (Aβ) burden, in parallel with altered PINK1/Parkin-associated mitophagy markers. These findings link a salt-rich diet to cognitive dysfunction, and suggest that enhancing PINK1/Parkin-mediated mitophagy may counteract the harmful effects of HSD on the brain. Therefore, the PINK1/Parkin mitophagy may be a potential target for combating the harmful effects on the brain caused by HSD or other diseases related to mitophagy.