Robo4 and its relationship to Alzheimer's Disease

Abstract

Aging is associated with the impairment of the neurovascular unit, and this potentially leads to increased Alzheimer's disease pathology and cognitive impairment. A specific axon guidance receptor, Robo4, is important in maintaining the structure and restrictive barrier of the blood-brain barrier (BBB). Therefore, Robo4 signaling pathways may potentially be a valuable target for therapeutic treatments of AD. In the present study, we studied Robo4 knockout (Robo4 -/-) and wild type (Robo4 +/+) mice crossed with mice containing mutations in amyloid precursor protein (APP), leading to greater aberrant amyloid-beta production. We predicted that the knockout of Robo4 will increase BBB permeability, leading to increased Alzheimer’s disease-related neuropathology and cognitive dysfunction. To examine the effect of aging, we studied young and old wildtype C57BL6 mice. We assessed cognitive function by conducting Nest Building tests and Morris Water Maze. We found that old C57BL6 mice had impaired cognitive function compared to young C57BL6 mice. However, when Robo4 x APP groups were compared, we found no differences in cognitive function. These preliminary results suggest that aging has a stronger effect on cognitive function than Robo4 knockout. Additional studies are needed to determine the effect of Robo4 knockout on blood-brain barrier permeability and amyloid-beta accumulation.