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Extracorporeal apheresis therapy for Alzheimer disease—targeting lipids, stress, and inflammation

Molecular Psychiatry volume 25, pages 275–282 (2020)Cite this article

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Abstract

Current therapeutic approaches to Alzheimer disease (AD) remain disappointing and, hence, there is an urgent need for effective treatments. Here, we provide a perspective review on the emerging role of “metabolic inflammation” and stress as a key factor in the pathogenesis of AD and propose a novel rationale for correction of metabolic inflammation, increase resilience and potentially slow-down or halt the progression of the neurodegenerative process. Based on recent evidence and observations of an early pilot trial, we posit a potential use of extracorporeal apheresis in the prevention and treatment of AD. Apolipoprotein E, lipoprotein(a), oxidized LDL (low density lipoprotein)'s and large LDL particles, as well as other proinflammatory lipids and stress hormones such as cortisol, have been recognized as key factors in amyloid plaque formation and aggravation of AD. Extracorporeal lipoprotein apheresis systems employ well-established, powerful methods to provide an acute, reliable 60–80% reduction in the circulating concentration of these lipid classes and reduce acute cortisol levels. Following a double-membrane extracorporeal apheresis in patients with AD, there was a significant reduction of proinflammatory lipids, circulating cytokines, immune complexes, proinflammatory metals and toxic chaperones in patients with AD. On the basis of the above, we suggest designing clinical trials to assess the promising potential of such “cerebropheresis” treatment in patients with AD and, possibly, other neurodegenerative diseases.

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Acknowledgements

This work was supported by Transcampus and the Deutsche Forschungsgemeinschaft (GRK 2251/1, TRR 205/1).

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Authors and Affiliations

  1. Department of Medicine III, University Hospital Carl Gustav Carus, Dresden, Germany

    Stefan R. Bornstein, Sergey Tselmin, Ulrich Julius, Ulrike Schatz & George P. Chrousos

  2. Division of Diabetes & Nutritional Sciences, Faculty of Life Sciences & Medicine, King’s College London, London, UK

    Stefan R. Bornstein

  3. Klinik für Endokrinologie, Diabetologie und Klinische Ernährung, University Hospital, Zürich, Switzerland

    Stefan R. Bornstein

  4. Zentrums für Apherese- und Hämofiltration am INUS Tagesklinikum, Cham, Germany

    Karin Voit-Bak & Richard Straube

  5. Facharzt für Nervenheilkunde, Facharzt Psychiatrie und Psychotherapie, Paulmannshöher Strasse 17, 58515, Lüdenscheid, Germany

    Peter Rosenthal

  6. Lee Kong Chian School of Medicine, NTU Nanyang Technological University, Singapore, Singapore

    Bernhard O. Boehm

  7. Maurice Wohl Clinical Neuroscience Institute, Department of Basic and Clinical Neuroscience, Institute of Psychiatry, Psychology and Neuroscience, King’s College London, London, UK

    Sandrine Thuret

  8. Center for Regenerative Therapies Dresden (CRTD), Technische Universität Dresden, 01307, Dresden, Germany

    Gerd Kempermann

  9. German Center for Neurodegenerative Diseases (DZNE) Dresden, 01307, Dresden, Germany

    Gerd Kempermann

  10. Department of Neurology University Hospital Carl Gustav Carus, Technische Universität Dresden, 01307, Dresden, Germany

    Heinz Reichmann

  11. University Research Institute of Maternal and Child Health & Precision Medicine, National and Kapodistrian University of Athens, Athens, Greece

    George P. Chrousos

  12. State University of New York Upstate Medical University, Syracuse, NY, USA

    Julio Licinio & Ma-Li Wong

  13. Departments of Pathology, Department of Medicine, Sylvester Comprehensive Cancer Center, Miller School of Medicine, University of Miami, Miami, FL, USA

    Andrew V. Schally

  14. Veterans Affairs Medical Center, Miami, FL, USA

    Andrew V. Schally

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Bornstein, S.R., Voit-Bak, K., Rosenthal, P. et al. Extracorporeal apheresis therapy for Alzheimer disease—targeting lipids, stress, and inflammation. Mol Psychiatry 25, 275–282 (2020). https://doi.org/10.1038/s41380-019-0542-x

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