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

• Published in: Molecular psychiatry Vol. 25; no. 2; pp. 275 - 282
• Main Authors: Bornstein, Stefan R., Voit-Bak, Karin, Rosenthal, Peter, Tselmin, Sergey, Julius, Ulrich, Schatz, Ulrike, Boehm, Bernhard O., Thuret, Sandrine, Kempermann, Gerd, Reichmann, Heinz, Chrousos, George P., Licinio, Julio, Wong, Ma-Li, Schally, Andrew V., Straube, Richard
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 01-02-2020; Nature Publishing Group
• Subjects: 692/699; 692/699/476; Advertising executives; Alzheimer Disease - therapy; Alzheimer's disease; Amyloid; Antigen-antibody complexes; Antilipemic agents; Apheresis; Apolipoprotein E; Apolipoproteins; Behavioral Sciences; Biological Psychology; Blood Component Removal - methods; Chaperones; Cholesterol, LDL - blood; Clinical trials; Corticosteroids; Cytokines; Development and progression; Drug therapy; Health aspects; Humans; Inflammation; Inflammation - metabolism; Lipid Metabolism - physiology; Lipids; Lipids - physiology; Lipoprotein A; Lipoproteins; Lipoproteins, LDL - blood; Liraglutide; Low density lipoprotein; Low density lipoproteins; Medical colleges; Medical research; Medicine; Medicine & Public Health; Medicine, Experimental; Metabolism; Metals; Neurodegenerative diseases; Neurosciences; Oxidation resistance; Pathogenesis; Patients; Perspective; Pharmacotherapy; Prevention; Psychiatry; Stress; Stress, Psychological - physiopathology; Germany
• ISSN: 1359-4184; 1476-5578
• DOI: 10.1038/s41380-019-0542-x

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.