Neuroinflammation in Alzheimer’s disease: insights from peripheral immune cells Alzheimer’s disease (AD) is a serious brain disorder characterized by the presence of beta-amyloid plaques, tau pathology, inflammation, neurodegeneration, and cerebrovascular dysfunction. Chronic neuroinflammation, breaches in the blood-brain barrier (BBB), and increased levels of inflammatory mediators are central to the pathogenesis of AD. These factors promote the penetration of immune cells into the brain, potentially exacerbating clinical symptoms and neuronal death in AD patients. While microglia, the resident immune cells of the central nervous system (CNS), play a crucial role in AD, recent evidence suggests the infiltration of cerebral vessels and parenchyma by peripheral immune cells, including neutrophils, T lymphocytes, B lymphocytes, NK cells, and monocytes in AD. These cells participate in the regulation of immunity and inflammation, which is expected to play a huge role in future immunotherapy. Given the crucial role of peripheral immune cells in AD, this article seeks to offer a comprehensive overview of their contributions to neuroinflammation in the disease. Understanding the role of these cells in the neuroinflammatory response is vital for developing new diagnostic markers and therapeutic targets to enhance the diagnosis and treatment of AD patients. Keywords: Alzheimer's disease, Neuroinflammation, Neutrophils, T lymphocytes, B lymphocytes, NK cells The pathology of AD is significantly influenced by peripheral immune cells including neutrophils, T lymphocytes, B lymphocytes, and NK cells. Activated neutrophils can accumulate and adhere to vascular walls, potentially obstructing blood flow. They can also enter brain tissue through a compromised BBB, where they worsen the disease by releasing inflammatory cytokines and neutrophil extracellular traps (NETs). T lymphocytes indirectly contribute to disease progression by affecting glial cell function. B lymphocytes impact the progression of the disease by secreting inflammatory cytokines and antibodies, which then regulate behavior. NK cells also contribute to the disease's progression through interactions with microglia and the release of inflammatory mediators. These complex cellular activities drive the pathogenesis of AD and suggest potential targets for therapeutic intervention. Neutrophils in AD: Neutrophils are the primary reservoir of neutrophils in the bone marrow, and they are also present in the bloodstream and the marrow adjacent to the cranial bones within the CNS. Generally, neutrophils circulate within blood vessels and face difficulty traversing the BBB to enter the brain. Consequently, circulating neutrophils lack robust cell adhesion molecules, which prevents their infiltration into the brain parenchyma. In patients with AD, a systemic inflammatory response coupled with a compromised BBB potentially activates neutrophils, facilitating their infiltration into the brain parenchyma. Numerous studies indicate heightened neutrophil activation in the bloodstream of AD patients, evidenced by increased reactive oxygen species (ROSNeuroinflammation in Alzheimer’s disease: insights from peripheral immune cells Alzheimer’s disease (AD) is a serious brain disorder characterized by the presence of beta-amyloid plaques, tau pathology, inflammation, neurodegeneration, and cerebrovascular dysfunction. Chronic neuroinflammation, breaches in the blood-brain barrier (BBB), and increased levels of inflammatory mediators are central to the pathogenesis of AD. These factors promote the penetration of immune cells into the brain, potentially exacerbating clinical symptoms and neuronal death in AD patients. While microglia, the resident immune cells of the central nervous system (CNS), play a crucial role in AD, recent evidence suggests the infiltration of cerebral vessels and parenchyma by peripheral immune cells, including neutrophils, T lymphocytes, B lymphocytes, NK cells, and monocytes in AD. These cells participate in the regulation of immunity and inflammation, which is expected to play a huge role in future immunotherapy. Given the crucial role of peripheral immune cells in AD, this article seeks to offer a comprehensive overview of their contributions to neuroinflammation in the disease. Understanding the role of these cells in the neuroinflammatory response is vital for developing new diagnostic markers and therapeutic targets to enhance the diagnosis and treatment of AD patients. Keywords: Alzheimer's disease, Neuroinflammation, Neutrophils, T lymphocytes, B lymphocytes, NK cells The pathology of AD is significantly influenced by peripheral immune cells including neutrophils, T lymphocytes, B lymphocytes, and NK cells. Activated neutrophils can accumulate and adhere to vascular walls, potentially obstructing blood flow. They can also enter brain tissue through a compromised BBB, where they worsen the disease by releasing inflammatory cytokines and neutrophil extracellular traps (NETs). T lymphocytes indirectly contribute to disease progression by affecting glial cell function. B lymphocytes impact the progression of the disease by secreting inflammatory cytokines and antibodies, which then regulate behavior. NK cells also contribute to the disease's progression through interactions with microglia and the release of inflammatory mediators. These complex cellular activities drive the pathogenesis of AD and suggest potential targets for therapeutic intervention. Neutrophils in AD: Neutrophils are the primary reservoir of neutrophils in the bone marrow, and they are also present in the bloodstream and the marrow adjacent to the cranial bones within the CNS. Generally, neutrophils circulate within blood vessels and face difficulty traversing the BBB to enter the brain. Consequently, circulating neutrophils lack robust cell adhesion molecules, which prevents their infiltration into the brain parenchyma. In patients with AD, a systemic inflammatory response coupled with a compromised BBB potentially activates neutrophils, facilitating their infiltration into the brain parenchyma. Numerous studies indicate heightened neutrophil activation in the bloodstream of AD patients, evidenced by increased reactive oxygen species (ROS