Neurodegenerative diseases (NDDs) are associated with the accumulation of a range of misfolded proteins across the central nervous system and related autoimmune responses, including the generation of antibodies and the activation of immune cells. Both innate and adaptive immunity become mobilized, leading to cellular and humoral effects. The role of humoral immunity in disease onset and progression remains to be elucidated with rising evidence suggestive of positive (protection, repair) and negative (injury, toxicity) outcomes. In this study, we review advances in research of neuron-targeting autoantibodies in the most prevalent NDDs. We discuss their biological origin, molecular diversity and changes in the course of diseases, consider their relevance to the initiation and progression of pathology as well as diagnostic and prognostic significance. It is suggested that the emerging autoimmune aspects of NDDs not only could facilitate the early detection but also might help to elucidate previously unknown facets of pathobiology with relevance to the development of precision medicine.

• Keywords
• Fluid biomarkers, autoimmunity, dementia, differential diagnosis, immunoglobins,
• MeSH
• Autoimmunity MeSH
• Autoantibodies * MeSH
• Biomarkers MeSH
• Humans MeSH
• Neurodegenerative Diseases * diagnosis   MeSH
• Neurons MeSH
• Proteins MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Review MeSH
• Research Support, N.I.H., Extramural MeSH
• Names of Substances
• Autoantibodies * MeSH
• Biomarkers MeSH
• Proteins MeSH

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