TY - JOUR

T1 - Myeloproliferative blood cancers as a human neuroinflammation model for development of Alzheimer's disease

T2 - evidences and perspectives

AU - Hasselbalch, Hans C

AU - Skov, Vibe

AU - Kjær, Lasse

AU - Sørensen, Torben L

AU - Ellervik, Christina

AU - Wienecke, Troels

PY - 2020

Y1 - 2020

N2 - 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.

AB - 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.

U2 - 10.1186/s12974-020-01877-3

DO - 10.1186/s12974-020-01877-3

M3 - Review

C2 - 32829706

VL - 17

JO - Journal of Neuroinflammation

JF - Journal of Neuroinflammation

SN - 1742-2094

M1 - 248

ER -