Microglial, astrocytic, oligodendrocyte, B-/T-cell and neutrophil dysregulation in neuroinflammation of Alzheimer's disease and related dementias.

Wide number of basic, preclinical and clinical research have led to increase our knowledge on understanding the potential roles of neuroinflammation in neurodegenerative diseases such as Alzheimer's disease (AD). In fact, neuroinflammation is considered as one of the key pathological factors of neuronal dysfunction leading to dementia in AD and other forms of dementias or related dementias (RD). Central nervous system (CNS) network communicates and control the immune system signaling pathways within the brain as well as peripheral part of the body. Hence, disturbance in the physiological immune system regulation is susceptible to the etiology or pathogenesis of the diseases. Microglia, astrocytes, oligodendrocytes, B-/T-cells and neutrophils are potential regulatory cells in keeping our immune system in balance. The imbalance in the regulatory function of these cells results to inflammatory consequences and has direct or indirect influence in the AD trajectory. In the brain, neuroinflammation is strongly linked to the accumulation of Aβ plaques and tau tangles which lead to pathogenesis underlying dementia of AD. Currently, neuroinflammation is considered as one of the pathological hallmarks of AD, alongside Aβ plaques and tau tangles. Various research and review articles have described the dysregulation of immune system cells leading to neuroinflammation in AD and RD pathogenesis. However, how these immune cells become coordinately imbalanced in the disease pathogenesis has been rarely reported, which is necessary for deeper understanding of the disease pathology and therapeutic development. In this review, we intend to highlight and discuss the neuroinflammatory pathways mediated via dysregulation of microglia, astrocyte, oligodendrocyte, neutrophil, B-cell and T-cell functions, which leads to neuronal dysfunction, dementia or cognitive decline in AD and RD. We believe that the narrative in this review will be helpful in the future basic/clinical research and therapeutic development for AD and RD.