Neural cell-surface and intracellular autoantibodies in patients with cognitive impairment from a memory clinic cohort

Abstract

Abstract Autoantibody-associated cognitive impairment is an expanding field in geriatric psychiatry. We aim to assess the association between the presence of specific neural autoantibodies and cognitive performance in a memory clinic cohort. 154 patients with cognitive impairment were included between 2019 and 2020 presenting initially in a memory clinic. We evaluated their patient files retrospectively applying epidemiologic parameters, psychopathology, neuropsychology, intracellular and membrane-surface autoantibodies in serum and cerebrospinal fluid (CSF) and markers of neurodegeneration in CSF. In 26 of 154 patients, we searched for neural autoantibodies due to indicators for autoimmunity. In 15/26 (58%) of patients we detected serum and/or CSF autoantibodies. We identified autoantibodies against intracellular or cell-surface antigens in 7 of all 26 (27%) patients with cognitive dysfunction, although we cannot exclude patients with potential specific autoantibodies lacking autoimmune indicators. There were no significant differences between psychopathological and neuropsychological profiles in groups of patients with cognitive impairment comprising patients with autoantibodies (ABS + COG), no autoantibodies (ABS − COG), and Alzheimer’s disease (ADCOG). Concerning our CSF parameters, we detected intrathecal IgG synthesis in 14% of ABS + COG and in 13% of ABS − COG patients, whereas no intrathecal IgG synthesis was found in ADCOG patients. Furthermore, CSF Aß42 was significantly diminished in the ADCOG compared to the ABS + COG group (p < 0.05). In addition, the Aß42/40 ratio was lower in ADCOG patients than in the ABS + COG or ABS − COG group (p < 0.05). Our findings reveal the underestimated occurrence and autoantibodies’ potential role in patients presenting cognitive impairment. Furthermore, the patients with possible Alzheimer’s disease might be differentiated from autoantibody-positive patients via a reduced Aß42 and Aß42/40 ratio in the CSF. The antibody-type varies between patients to a relevant degree, thus demonstrating the need for more research to identify subgroup-specific phenotypes. These pilot study results open an avenue for improving diagnosis and treatment in a memory clinic.