Natural Anti-NMDAR1 autoantibodies associate with slowed decline of cognitive functions in Alzheimer’s diseases

TL;DR

Natural anti-NMDAR1 autoantibodies may slow cognitive decline in Alzheimer’s patients, with higher levels linked to better mental scores.

Contribution

A new method was developed to quantify low levels of natural anti-NMDAR1 autoantibodies and their association with cognitive function in Alzheimer’s.

Findings

AD patients with higher natural anti-NMDAR1 autoantibodies had significantly higher MMSE scores (23.5 vs. 21.4).

No significant MMSE differences were found in healthy controls with varying autoantibody levels.

Higher autoantibody levels correlated with better cognitive performance in AD patients.

Abstract

Low titers of blood circulating natural anti-NMDAR1 autoantibodies were reported in ~10% of the general human population. Their potential effects on NMDAR functions in the brain, however, remain unknown. We developed a new method to more accurately quantify these low titers of natural anti-NMDAR1 autoantibodies. After quantifying natural anti-NMDAR1 autoantibodies in the plasma of 324 subjects (163 healthy controls; 161 Alzheimer’s disease (AD) patients), I found that AD patients carrying higher levels of natural anti-NMDAR1 autoantibodies have significantly (p value: 0.0015) higher scores of Mini-Mental State Examination (MMSE score: 23.5) than AD patients carrying lower levels of natural anti-NMDAR1 autoantibodies (MMSE score: 21.4). No significant differences in MMSE scores were, however, found between healthy controls with either higher or lower levels of natural anti-NMDAR1 autoantibodies, indicating little harmful effect of the autoantibodies. Consistently, superior cognitive performances were found in AD patients carrying higher levels of natural anti-NMDAR1 autoantibodies in comparison with AD patients carrying lower levels of the autoantibodies. Although this association is intriguing, a causal relationship between natural anti-NMDAR1 autoantibodies and neuroprotection has not yet been established. Since anti-NMDAR1 autoantibodies can bind NMDA receptors to suppress glutamate excitotoxicity in the brain, natural anti-NMDAR1 autoantibodies may have neuroprotective effects against cognitive decline in AD patients.

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