Circulating autoantibodies against the NR2 peptide of the NMDA receptor are associated with subclinical brain damage in hypertensive patients with other pre-existing conditions for vascular risk.

Arterial hypertension (HT) and other vascular pre-existing conditions (PEC) generate asymptomatic brain damage which increases the occurrence of stroke and cognitive decline. The aim of this work was to explore if serum antibodies against the NR2 subunit of the NMDA receptor (NR2Ab) could predict subclinical brain damage (SBD) in hypertensive patients with PEC. Forty seven neurologically asymptomatic hypertensive subjects were classified according to the number of PEC (retinopathy, overweight/obesity, diabetes mellitus and dyslipidemia). NR2A/B Ab were measured in serum employing an ELISA method. 3.0-T Brain MRI imaging was performed, and visual ratings of white matter hyperintensities (WMH) and counts of dilated Virchow-Robin spaces (DVRS) and lacunes were obtained. Brain atrophy was evaluated with cortical thickness measurements and linear measures. Higher levels of NR2Ab were associated with more severe periventricular WMH (PWMH), more DVRS and more severe SBD; while greater frontal interhemispheric fissure width (IHFW), as a linear measure of frontal atrophy, was inversely related with NR2Ab. Overall and regional cortical thickness were not significantly associated with NR2 Ab. A multivariate analyses showed that IHFW and PWMH were the only variables independently associated with serum NR2Ab concentration. ROC analysis revealed that NR2Ab (cutoff: 1.7ng/ml) predicted PWMH with a sensitivity and specificity of 65% and 87% respectively. CONCLUSIONS: Serum NR2Ab levels may reflect SBD in HT subjects with PEC, especially in younger populations at risk, where age-related cortical atrophy has not yet been fully established.