Salvianolic acid B ameliorates retinal deficits in an early-stage Alzheimer's disease mouse model through downregulating BACE1 and A beta generation

Alzheimer's disease (AD) is a neurodegenerative disease with subtle onset, early diagnosis remains challenging. Accumulating evidence suggests that the emergence of retinal damage in AD precedes cognitive impairment, and may serve as a critical indicator for early diagnosis and disease progression. Salvianolic acid B (Sal B), a bioactive compound isolated from the traditional Chinese medicinal herb Salvia miltiorrhiza, has been shown promise in treating neurodegenerative diseases, such as AD and Parkinson's disease. In this study we investigated the therapeutic effects of Sal B on retinopathy in early-stage AD. One-month-old transgenic mice carrying five familial AD mutations (5xFAD) were treated with Sal B (20 mg.kg(-1).d(-1), i.g.) for 3 months. At the end of treatment, retinal function and structure were assessed, cognitive function was evaluated in Morris water maze test. We showed that 4-month-old 5xFAD mice displayed distinct structural and functional deficits in the retinas, which were significantly ameliorated by Sal B treatment. In contrast, untreated, 4-month-old 5xFAD mice did not exhibit cognitive impairment compared to wild-type mice. In SH-SY5Y-APP751 cells, we demonstrated that Sal B (10 mu M) significantly decreased BACE1 expression and sorting into the Golgi apparatus, thereby reducing A beta generation by inhibiting the beta-cleavage of APP. Moreover, we found that Sal B effectively attenuated microglial activation and the associated inflammatory cytokine release induced by A beta plaque deposition in the retinas of 5xFAD mice. Taken together, our results demonstrate that functional impairments in the retina occur before cognitive decline, suggesting that the retina is a valuable reference for early diagnosis of AD. Sal B ameliorates retinal deficits by regulating APP processing and A beta generation in early AD, which is a potential therapeutic intervention for early AD treatment.

Automated summary

Alzheimer's disease (AD) is a neurodegenerative disease that is difficult to diagnose early. Retinal damage in AD may occur before cognitive impairment and could be used as an indicator for early diagnosis. Salvianolic acid B (Sal B), a compound from Salvia miltiorrhiza, has shown promise in treating AD. This study demonstrated that Sal B treatment ameliorated retinal deficits in early-stage AD, suggesting its potential as a therapeutic intervention for early AD treatment.