In Alzheimer's disease (AD), tau pathology manifested by the accumulation of intraneuronal tangles and soluble toxic oligomers emerges as a promising therapeutic target. Multiple anti-tau antibodies inhibiting the formation and propagation of cytotoxic tau or promoting its clearance and degradation have been tested in clinical trials, albeit with the inconclusive outcome. Antibodies against tau protein have been documented both in the brain circulatory system and at the periphery, but their origin and role under normal conditions and in AD remain unclear. While it is tempting to assign them a protective role in regulating tau level and removal of toxic variants, the supportive evidence remains sporadic, requiring systematic analysis and critical evaluation. Herein, we review recent data showing the occurrence of tau-reactive antibodies in the brain and peripheral circulation and discuss their origin and significance in tau clearance. Based on the emerging evidence, we cautiously propose that impairments of tau clearance at the periphery by humoral immunity might aggravate the tau pathology in the central nervous system, with implication for the neurodegenerative process of AD.

• MeSH
• Alzheimer Disease etiology   metabolism   pathology   therapy   MeSH
• Autoantigens immunology   MeSH
• Autoantibodies blood   immunology   MeSH
• Immunotherapy MeSH
• Immunoglobulins, Intravenous therapeutic use   MeSH
• Humans MeSH
• Disease Susceptibility * MeSH
• tau Proteins immunology   metabolism   MeSH
• Animals MeSH
• Check Tag
• Humans MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Review MeSH
• Names of Substances
• Autoantigens MeSH
• Autoantibodies MeSH
• Immunoglobulins, Intravenous MeSH
• tau Proteins MeSH