Natural Killer Cells in Alzheimer's Disease: From Foe to Friend

The neuroinflammatory aspect of Alzheimer's disease (AD) has been largely focused on microglia, the innate immune cells of the brain; however, recent evidence increasingly points to the importance of multiple alterations in the systemic immune response during disease development. Natural killer (NK) cells are also components of innate immunity, whose role in AD pathogenesis has been sporadically investigated and often conflicting results have been reported. Recent clinical trial has suggested the potential beneficial effects of AD immunotherapy based on ex vivo-expanded, genetically unmodified, NK cells. This has led to increased interest in understanding the function of these cells in the central nervous system in both physiological and pathological contexts such as AD. Considering that AD is predominantly a disease of the elderly population, in this review, we summarized the current state of knowledge on the physiological changes that occur in the NK cell compartment during the normal aging process and the pathophysiological alterations that occur throughout the AD continuum that could potentially explain the therapeutic efficacy of these cells.