Peripheral Mononuclear Cell Rejuvenation for Senescence Surveillance in Alzheimer Disease

Marco      Malavolta; Andrea      Basso; Francesco      Piacenza; Laura      Costarelli; Robertina      Giacconi; Eugenio      Mocchegiani

Abstract

Recent observations have pointed out that microglia, astrocytes and cerebrovascular endothelial cells senescence might contribute to the onset or progression of sporadic AD. The accumulation of senescent dysfunctional microglia or senescence related changes of other cells within CNS could be causally implicated in AD and age-related dysfunction and their efficient removal could represent a pivotal mechanism to prevent or delay neurodegeneration. The question how senescent cells are cleared from CNS has been poorly investigated, even though it is reasonable to believe that resident microglia is involved in this task. However, accumulating evidence now support the idea that assistance by peripheral mononuclear phagocytes (MP) in AD could be essential to control local brain inflammation and remove Abeta depots. Based on the current knowledge it is reasonable to hypothesize that senescence surveillance might be among the tasks that blood derived MP are called to envelop in the CNS during particular conditions, especially in the case senescent microglia is not able to achieve this task properly. However, age-related dysfunctions of these players of innate immunity could lead to depict a series of events that synergically with microglia and other CNS cells senescence could lead to a rapid progression of the disease. Hence, the design of intervention aimed at targeting accumulating senescent cells by rejuvenation of peripheral MP function seems an attractive tool that perhaps would also help to clarify the processes involved in senescence surveillance in normal and AD brain.

Keywords: Cell senescence, Alzheimer, peripheral mononuclear phagocytes, microglia, rejuvenation, astrocytes, sporadic AD, neurodegeneration, CNS, innate immunity