Myeloproliferative blood cancers as a human neuroinflammation model for development of Alzheimer's disease: evidences and perspectives.

ABSTRACT

Chronic inflammation and involvement of myeloid blood cells are associated with the development of Alzheimer's disease (AD). Chronic inflammation is a highly important driving force for the development and progression of the chronic myeloproliferative blood cancers (MPNs), which are characterized by repeated thrombotic episodes years before MPN-diagnosis, being elicited by elevated erythrocytes, leukocytes, and platelets. Mutations in blood cells, the JAK2V617F and TET2-mutations, contribute to the inflammatory and thrombogenic state. Herein, we discuss the MPNs as a human neuroinflammation model for AD development, taking into account the many shared cellular mechanisms for reduction in cerebral blood, including capillary stalling with plugging of blood cells in the cerebral microcirculation. The therapeutic consequences of an association between MPNs and AD are immense, including reduction in elevated cell counts by interferon-alpha2 or hydroxyurea and targeting the chronic inflammatory state by JAK1-2 inhibitors, e.g., ruxolitinib, in the future treatment of AD.