Regenerative therapy for Alzheimer's disease and cerebral amyloid angiopathy

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Dementia will become one of the most important health problems worldwide. The discouraging results of the immunotherapy clinical trials for Alzheimer's disease have shifted scientific attention from the mechanism underlying beta amyloid (Abeta) synthesis toward clearance. Arterial pulsations may be the motive force for the drainage of interstitial fluid and solutes. As arteries stiffen with age or with other co-morbid factors, the amplitude of pulsations is reduced, perivascular drainage of Abeta becomes less efficient, and insoluble Abeta is deposited in the drainage pathways. Therefore, therapeutic strategies that enhance the patency of this perivascular drainage pathway with vasoactive drugs may facilitate Abeta removal and help prevent cognitive decline in the elderly. Based on this emerging paradigm, we will start a clinical trial to determine whether such a hemodynamic strategy is effective to halt cognitive decline as a preemptive medicine.