L-DOPA regulates neuroinflammation and Aβ pathology through NEP and ADAM17 in a mouse model of AD

Abstract

Dopamine plays important roles in cognitive function and inflammation and therefore is involved in the pathogenesis of neurodegenerative diseases, including Alzheimer's disease (AD). Drugs that increase or maintain dopamine levels in the brain could be a therapeutic strategy for AD. However, the effects of dopamine and its precursor levodopa (L-DOPA) on A beta/tau pathology in vivo and the underlying molecular mechanisms have not been studied in detail. Here, we investigated whether L-DOPA treatment alters neuroinflammation, A beta pathology, and tau phosphorylation in 5xFAD mice, a model of AD. We found that L-DOPA administration significantly reduced microgliosis and astrogliosis in 5xFAD mice. In addition, L-DOPA treatment significantly decreased A beta plaque number by upregulating NEP and ADAM17 levels in 5xFAD mice. However, L-DOPA-treated 5xFAD mice did not exhibit changes in tau hyperphosphorylation or tau kinase levels. These data suggest that L-DOPA alleviates neuroinflammatory responses and A beta pathology but not tau pathology in this mouse model of AD.