Rho‐associated protein kinases as therapeutic targets for both vascular and parenchymal pathologies in Alzheimer's disease

The causes of late‐onset Alzheimer's disease are unclear and likely multifactorial. Rho‐associated protein kinases (ROCKs) are ubiquitously expressed signaling messengers that mediate a wide array of cellular processes. Interestingly, they play an important role in several vascular and brain pathologies implicated in Alzheimer's etiology, including hypertension, hypercholesterolemia, blood–brain barrier disruption, oxidative stress, deposition of vascular and parenchymal amyloid‐beta peptides, tau hyperphosphorylation, and cognitive decline. The current review summarizes the functions of ROCKs with respect to the various risk factors and pathologies on both sides of the blood–brain barrier and present support for targeting ROCK signaling as a multifactorial and multi‐effect approach for the prevention and amelioration of late‐onset Alzheimer's disease. This article is part of the Special Issue “Vascular Dementia”. We reviewed evidence that supports using inhibitors of ROCKs to treat Alzheimer Disease (AD). The multifaceted AD pathologies on both sides of the blood–brain barrier can be ameliorated by inhibition of ROCKs providing a potentially viable therapeutic strategy. This article is part of the Special Issue “Vascular Dementia”.