The role of the immune system in Alzheimer's disease

Alzheimer's disease (AD) is the most common neurodegenerative disorder where the accumulation of amyloid plaques and the formation of tau tangles are the prominent pathological hallmarks. Increasing preclinical and clinical studies have revealed that different components of the immune system may act as important contributors to AD etiology and pathogenesis. The recognition of misfolded Aβ and tau by immune cells can trigger a series of complex immune responses in AD, and then lead to neuroinflammation and neurodegeneration. In parallel, genome-wide association studies have also identified several immune related loci associated with increased - risk of AD by interfering with the function of immune cells. Other immune related factors, such as impaired immunometabolism, defective meningeal lymphatic vessels and autoimmunity might also be involved in the pathogenesis of AD. Here, we review the data showing the alterations of immune cells in the AD trajectory and seek to demonstrate the crosstalk between the immune cell dysfunction and AD pathology. We then discuss the most relevant research findings in regards to the influences of gene susceptibility of immune cells for AD. We also consider impaired meningeal lymphatics, immunometabolism and autoimmune mechanisms in AD. In addition, immune related biomarkers and immunotherapies for AD are also mentioned in order to offer novel insights for future research.