In a healthy brain, neuroinflammation, controlled by the main intermediary for the immune response microglia and astrocytes, contributes to maintain physiological functions such as secretion of neurotrophic factors, removal of cell tau and amyloid-β (Aβ) debris, and local homeostasis. When the immune response becomes chronic, it can become pathological and fuel neuroinflammation, causing glial cells to malfunction and not perform their function of clearing debris, resulting in further damage to neurons. Multiple studies highlight that an intense crosstalk is activated between peripheral blood white cells (PBWCs) and central nervous system (CNS). Nevertheless, how PBWC can be carriers of biomarkers of the CNS neuropathological states it is still far to be completely known. In this work, we aimed to observe how PBWC content could be related to moderate-severity of DAT in order to have early signals from of pathological neurodegeneration brain initiate. Protein analysis have been performed in PBWC of Mild Cognitive Impairment (MCI) and DAT patients in respect to those of healthy controls and differently expressed proteins have been investigated. Our data showed a deregulation of pathways involved in neurodegeneration since from MCI level and deregulated proteins that can be considered markers for DAT onset and progression.