Role of a β Transport and clearance in the pathogenesis and treatment of alzheimer's disease

In addition to Aβ production, the factors that control Aβ degradation, clearance, transport, and fibrillogenesis play an important role in the process by which Aβ converts from soluble forms to both soluble and insoluble forms that aggregate in the brain and contribute to AD and CAA pathogenesis. Studies summarized herein suggest that transport of Aβ between brain and blood and blood and brain plays an important role in regulating Aβ metabolism and that specific molecules such as LRP, RAGE, and apoE regulate this process. In addition, apoE, acting as a chaperone for both soluble and fibrillar Aβ can modulate Aβ clearance, transport, and fibrillogenesis and in doing so, plays an important role in AD and CAA pathogenesis. Further studies to sort out the cell biology of these clearance mechanisms as well as which other molecules are involved in these processes will provide important additional insights into AD and CAA pathogenesis.