Neuronal Surface and Intracellular Antibodies in Mild Cognitive Impairment Due to Alzheimer Disease: Preserved Brain Metabolism on 18 F-FDG-PET

BACKGROUND AND PURPOSE: Neuronal autoantibodies, which can mediate pathogenic mechanism in autoimmune encephalitis, are increasingly observed in mild cognitive impairment (MCI), yet their diagnostic or phenotypic implications in neurodegeneration remain unclear. This study aimed to evaluate the clinical and neuroimaging characteristics of antibody-positive MCI. MATERIALS AND METHODS: This cross-sectional study included 97 patients diagnosed with MCI. Antibody was assessed by cell-based assays in both CSF and serum. Clinical features were systematically compared between antibody-positive and antibody-negative groups. Semiquantitative analyses of 18F-FDG-PET and 11C-Pittsburgh compound B (11C-PIB)-PET were performed among 20 amyloid-positive patients with MCI. All images underwent standardized preprocessing, with standardized uptake value ratios calculated using cerebellar gray matter as reference. Group-wise differences of whole-brain and ROI analyses (frontal, parietal, temporal, occipital lobes) were analyzed. RESULTS: Neuronal antibodies were detected in 10 patients (10.3%), including anti-GABABR (n=1), anti-SOX-1 (n=3), anti-Ri (n=3), anti-Titin (n=3), and anti-Amphiphysin (n=1). Clinical profiles were highly comparable between groups; antibody-positive patients only demonstrated significantly higher abnormal tumor markers (P = .014). Compared with the antibody-negative group, the antibody-positive group exhibited relatively preserved metabolism on 18F-FDG-PET (P = .035), predominantly in the right parietal lobe (P = .030). Further subregion analysis identified the right postcentral gyrus and supramarginal gyrus as focal hubs. No significant group differences were observed on 11C-PIB-PET. CONCLUSIONS: Antibody-positive MCI showed relatively preserved metabolism on 18F-FDG-PET, despite indistinguishable clinical features. Identification of the antibody-positive group may provide novel insights into possible antibody-mediated pathogenesis in neurodegeneration.