Large-scale seroepidemiology identifies a nephro-vascular syndrome associated with autoimmune reactivity to tau
Magalhaes, A. D.; Emmenegger, M.; De Cecco, E.; Carta, M.; Frontzek, K.; Chincisan, A.; Hornemann, S.; Aguzzi, A.
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Intraneuronal aggregates of the microtubule-associated protein tau play a pivotal role in Alzheimers disease and several other neurodegenerative syndromes. Anti-tau antibodies can reduce pathology in mouse models of neurodegeneration and are currently tested in humans. Here, we performed a large-scale seroepidemiological search for anti-tau IgG autoantibodies ({tau}) on 40,497 human plasma samples. High-titer {tau}+ individuals were surprisingly prevalent, with hospital patients being three times more likely to be {tau}+ (EC50 [≥] 26; a nominal dilution of > 1/64) than healthy blood donors (4.8% vs 1.6%). The prevalence increased with age over 70 years-old (RR 1.26, 95%CI 1.11-1.43, P<0.001) and was higher for women (RR 1.20, 95%CI 1.07-1.39, P=0.002). The autoantibodies bound selectively to tau, inhibited tau aggregation in vitro, and interfered with tau detection in plasma samples. No association was found between {tau} autoantibodies and neurological disorders. Instead, tau autoreactivity showed a significant association with kidney and urinary disorders (adjusted RR 1.27, 95%CI 1.10-1.45, P=0.001 and 1.40, 95%CI 1.20-1.63, P<0.001, respectively). These results suggest a previously unrecognized association between {tau} autoimmunity and extraneural diseases.
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