Cholesterol crystal formation and embolism in the central nervous system and their potential role in Alzheimer's disease

The brain and nervous tissues are very rich in cholesterol with local sterol biosynthesis being the primary source. The production of cholesterol in the brain may also lead to cholesterol crystal formation that in turn can cause inflammation which potentially can contribute to Alzheimer's disease. In this review we provide examples of cholesterol crystals (CCs) in human brains of Alzheimer patients. Moreover, cholesterol in the arterial circulation is also a major contributor to brain pathology. Specifically, CCs embolization released during plaque rupture may lead to reduced cognitive function, transient ischemic attacks, and ischemic strokes. Ischemic strokes can be caused by either thrombotic emboli from atrial fibrillation or CC emboli and platelets from ruptured plaques in the carotid arteries and aortic arch. CC emboli can cause blood flow obstruction, localized inflammation, and vasospasm of the local arterial vasculature, all contributing to ischemia and brain injury. Prevention and treatment of CC emboli with statins and aspirin has been found to be effective. Moreover, previous studies have demonstrated that both statins and aspirin can dissolve CCs. Thus, preventing formation and/or dissolving CCs could potentially be effective in reducing end organ injury induced by both CCs formation as well as CCs emboli. Although further investigation with human studies remain lacking, recent studies have demonstrated prevention of thrombus formation induced by CCs may also provide another approach to inhibiting end-organ ischemic injury.