Vascular primary cilia in the pathogenesis of hypertension and Alzheimer's Disease

Primary cilia are microtubule‐based organelles, extending from the surface of cells to sense extracellular signaling cues. We demonstrated that the inability of endothelial cilia to sense and transmit fluid‐shear stress can lead to nitric oxide (NO) deficiency and cause vascular HTN. HTN can cause brain microvascular endothelial mechanical stress, damage the neurovascular unit, and ultimately induce cognitive impairment, contributing to the progression of AD. It is well documented that decreased biosynthesis of NO contributes to cerebral amyloid angiopathy in AD patients through increased deposition of Aβ. Disruption of the cholinergic neurotransmitter pathway, which is important for cognition, memory and learning abilities has been reported in AD patients. However, the connection between cilia and mAChR signaling in the brain has never been investigated. We propose a bold idea to look at the pathophysiological roles of cerebrovascular ciliary receptors in BP and AD.