Berg Brain Entry and Exit Consortium: Direct Migration of Myeloid Cells from the Skull Marrow to the Brain Through Anatomical Channels: Adding Fuel to the Fire in Alzheimer’s Disease

There are critical unmet needs for early diagnosis, prevention and cure in Alzheimer’s disease. After decades of efforts focused on reducing abnormally aggregated amyloid and tau proteins that accumulate in the brains of patients with AD, recent research now is directed at understanding the inflammation surrounding these aggregates and leading to novel hypotheses. Inflammation not only relies on the defense cells that permanently reside in the brain, but also on the circulating white blood cells that are produced and stored in the bone marrow. Under specific circumstances, circulating white blood cells can enter the brain and promote inflammation. Several routes are available for these cells to enter the brain. We recently discovered that one of these routes is a network of channels connecting the marrow located in the skull bone and the brain. This route provides a direct supply of white blood cells from the skull marrow to the brain. Even though this may promote inflammation in chronic cerebral diseases, it has not been explored yet in this context. Here we propose to use new technologies to investigate the relevance of the skull marrow-brain connections in AD. This includes not only methods optimized in our laboratory, but also techniques developed by other researchers gathered in this consortium. Through this work, we aim to identify novel modalities for Alzheimer’s patients’ care.