Longitudinally persisting KCNA2-autoantibodies in mild amnestic dementia with Alzheimer´s pathology - Report and literature review.

Claudia Bartels, Bianca Teegen, Niels Hansen, Jens Wiltfang, Sina Hirschel, Janosch Fox, Dirk Fitzner

Journal: Behavioural brain research 2025;482():115437

PMID: 39855473

Abstract

BACKGROUND

Neural autoantibodies are being increasingly detected in conjunction with neurodegenerative dementias such as Alzheimer's disease dementia (AD), yet their significance is not well clarified. In this case report, we report the previously unreported long-lasting persistence of potassium voltage-gated channel subfamily A member 2 (KCNA2) antibodies in biomarker-supported AD.

METHODS

We report on a 77-year-old, male patient evaluated in our outpatient memory clinic of the Department of Psychiatry and Psychotherapy, University Medical Center Göttingen. Neuropsychological test results and autoantibody testing in serum over a period of 4-5 years is provided.

REPORT

Our patient exhibited mild dementia syndrome and was diagnosed with AD on the basis of a prototypical biomarker profile (reduced Aβ42/40 ratio and elevated p-tau181 protein in cerebrospinal fluid). Within a 5-year follow-up with regular visits to our memory clinic, we observed a nearly stable neuropsychological profile of mild, amnestic variant dementia that did not noticeably progress. KCNA2 autoantibodies were also detectable in serum over 4 years with increasing titers over time. Combined anti-dementia therapy with donepezil, multimodal therapy including non-pharmacological cognitive therapy, and immunotherapy with intravenous methylprednisolone was carried out as an individual treatment approach.

CONCLUSIONS

KCNA2 autoantibody persistence in biomarker-supported AD does not necessarily trigger a poor outcome in the long-term, as cognitive impairment did not progress subsequently. At the same time, mild immunotherapy did not result in less immunoreactivity in conjunction with the detection of KCNA2 autoantibodies. This detection of KCNA2 autoantibodies in AD could provide indices of a potentially benign long-term AD course that should be further evaluated in studies.

Copyright © 2025 The Authors. Published by Elsevier B.V. All rights reserved.

Address: Department of Psychiatry and Psychotherapy, University Medical Center Göttingen, Von-Siebold-Str. 5, Göttingen 37075, Germany. Electronic address: [email protected].; Clinical Immunological Laboratory, Groß Grönau, Germany.; Department of Psychiatry and Psychotherapy, University Medical Center Göttingen, Von-Siebold-Str. 5, Göttingen 37075, Germany.; Department of Neurology, University Medical Center Göttingen, Göttingen, Germany.; Department of Psychiatry and Psychotherapy, University Medical Center Göttingen, Von-Siebold-Str. 5, Göttingen 37075, Germany; German Center for Neurodegenerative Diseases (DZNE), Von-Siebold-Str. 3a, Göttingen 37075, Germany; Neurosciences and Signaling Group, Institute of Biomedicine (iBiMED), Department of Medical Sciences, University of Aveiro, Aveiro, Portugal.
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