# 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.

## Key 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.