Supporting this mechanism, several preclinical studies have indicated that neprilysin inhibition or sacubitril-containing regimens exacerbate amyloid-β deposition, microglial activation, and cognitive deficits compared to valsartan alone (Ali et al., 2023; Hersh and Rodgers, 2008; Zhang et al., 2024). This evidence concerns the gene MME and Cognitive impairment.