Inflammation and programmed cell death in Alzheimer's disease: comparison of the central nervous system and peripheral blood

Although the central nervous system (CNS) has been defined as a privileged site in Alzheimer’s disease (AD), periphery can be more than simply witness of events leading to neurodegeneration. The CNS and peripheral blood can mutually communicate through cells and factors trafficking from the circulation into the brain and vice versa. A number of articles have reviewed inflammatory profiles and programmed cell death (PCD) in AD, separately in the CNS and at the peripheral level. This review does not provide an exhaustive account of what has been published on inflammation and PCD in AD. Rather, the aim of this review is to focus on possible linkages between the central and the peripheral compartments during AD progression, by critically analyzing, in a comparative manner, phenomena occurring in the CNS as well as the peripheral blood. In fact, growing evidence suggests that CNS and peripheral inflammation might present common features in the disease. Microarrays and metabolomics revealed that dysfunction of the glycolytic and oxidative pathways is similar in the brain and in the periphery. Moreover, dysregulated autophagosome/lysosomal molecular machinery, both at the CNS and the peripheral level, in AD-related cell damage, has been observed. Possible implications of these observations have been discussed.