Tau autoimmunity associated with systemic disease

Tau autoimmunity is associated with vascular, kidney, and urinary disorders. A Swiss study found that anaemia, urinary disorders, chronic kidney disease, vascular disease, and diabetes are independent predictors of naturally occurring tau autoantibodies. These antibodies may be considered when evaluating Tau plasma levels in the differential diagnosis of dementia syndromes.

Tau is a microtubule-binding protein that is highly expressed in neurons. It plays a pivotal role in a variety of neurodegenerative diseases, including Alzheimer’s disease, progressive supranuclear palsy, and several other tauopathies. Tau antibodies against tau epitopes can reduce pathology and functional decline in animal models of tauopathies. These antibodies are currently tested in a range of clinical trials. Plasma natural anti-tau antibodies have been detected in serum and plasma of patients with Alzheimer’s disease and Parkinson’s disease, but also in controls without neurodegenerative diseases. Dr Andreia Magalhães (University of Zurich, Switzerland) and colleagues set out to investigate the prevalence of autoantibodies against tau and a possible association with neurological and other disorders [1].

Plasma samples of 24,339 patients were included, of which 1,169 (4.8%) were positive. Older age (RR 1.26; P=0.001) and female sex (RR 1.2; P=0.007) were associated with a higher risk of positivity. They identified the following conditions as independent predictors of naturally occurring tau autoantibodies:

• Anaemia (RR 1.43; 95% CI 1.17–1.74; P=0.001);
• Urinary disorders (RR 1.44; 95% CI 1.24–1.67; P=0.001);
• Chronic kidney disease (RR 1.30; 95% CI 1.13–1.48; P=0.001);
• Vascular disease (RR 1.50; 95% CI 1.28–1.76; P<0.001);
• Diabetes (RR 1.29; 95% CI 1.10–1.52; P=0.002).

“For the first time it is possible to describe new potential roles for natural anti-tau autoantibodies in other than central nervous system diseases,” explained Dr Magalhães. Numerous new studies show that clinical tests using plasma tau can be used for the differential diagnosis of several dementia syndromes; some of these tests are expected to reach the clinic soon. However, since antibodies against tau prolong the half-life of tau in plasma, patients who receive such antibodies experience an increase in their plasma tau level. “Therefore, we think anaemia, vascular comorbidities, and kidney and urinary diseases should be taken into consideration when evaluating plasma levels for the differential diagnosis of dementia syndromes,” concluded Dr Magalhães.

1. Magalhães A, et al. Naturally occurring plasma tau autoantibodies and risk of systemic disease. OPR-026, EAN 2022, 25–28 April, Vienna, Austria.

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Posted on 22 August, 2022