Large-scale seroepidemiology identifies a nephro-vascular syndrome associated with autoimmune reactivity to tau

The microtubule-associated protein tau is involved in several neurodegenerative diseases and is currently being investigated as a plasma biomarker for the detection and monitoring of Alzheimers disease and as an immunotherapeutical target in clinical trials. We assessed plasma anti-tau IgG reactivity in 40098 unselected patients visiting a university hospital and healthy blood donors. We found that 4.97% patients and 1.58% healthy donors had natural anti-tau antibody titers >1.8 log10(EC50). In a multivariate model, female sex (P<0.001), age (P<0.001), cystitis (RR 1.59, 95%CI 1.14-2.16, P=0.004), other urinary disorders (RR 1.23, 95%CI 1.03-1.45, P=0.018), chronic kidney disease (RR 1.20, 95%CI 1.01-1.41, P=0.033), arterial embolism and thrombosis (RR 1.56, 95%CI 1.02-2.25, P=0.026) and atherosclerosis (RR 1.35, 95%CI 1.09-1.1.66, P=0.004) were independent predictors of anti-tau autoantibodies. We therefore conclude that anti-tau autoimmunity is associated with a systemic syndrome that includes vascular, kidney and urinary disorders. The expression of tau in these extraneural tissues suggests a potential role of autoimmunity in this syndrome.