Sulforaphane suppresses Aβ accumulation and tau hyperphosphorylation in vascular cognitive impairment(VCI).

Abstract

Sulforaphane (Sfn) is a compound naturally found in cruciferous vegetables such as broccoli, Brussels sprouts, cabbage, and kale. It is well-known for its antioxidative and anti-inflammatory effects. Sfn has attracted attention for its potential health benefits, particularly its role in brain health and the potential prevention of dementia and neurodegeneration. Alzheimer's disease (AD) and vascular cognitive impairment (VCI) are the top two causes of dementia. Cerebral vascular lesions give rise to VCI and predispose neurons to degeneration and Alzheimer's disease (AD) by Aβ accumulation and tau hyperphosphorylation. In a rat model of VCI by permanent bilateral common carotid artery occlusion (2VO), we tested the protective effect of the phase II enzyme inducer sulforaphane (Sfn). Sfn ameliorates vascular cognitive deficits by reducing the typical white matter injury and neural atrophy pathological changes in VCI. Moreover, for the first time, we demonstrated that it effectively reduced Aβ and toxic p-tau accumulation in VCI. The protective mechanisms of Sfn involve the induction of HO-1 expression, activation of the Akt/GSK3β pathway, and modulation of amyloid precursor protein (APP) expression levels. Our data suggest that Sfn is a promising therapeutic compound to treat VCI and AD. It inhibits short-term neuron and white matter injuries as well as long-term Aβ and p-tau accumulation caused by cerebral vascular lesions.