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.
| Original language | English (US) |
|---|---|
| Journal | Molecular Psychiatry |
| DOIs | |
| State | Accepted/In press - Jan 1 2019 |
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ASJC Scopus subject areas
- Molecular Biology
- Psychiatry and Mental health
- Cellular and Molecular Neuroscience
Cite this
Extracorporeal apheresis therapy for Alzheimer disease—targeting lipids, stress, and inflammation. / 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.
In: Molecular Psychiatry, 01.01.2019.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Extracorporeal apheresis therapy for Alzheimer disease—targeting lipids, stress, and inflammation
AU - Bornstein, Stefan R.
AU - Voit-Bak, Karin
AU - Rosenthal, Peter
AU - Tselmin, Sergey
AU - Julius, Ulrich
AU - Schatz, Ulrike
AU - Boehm, Bernhard O.
AU - Thuret, Sandrine
AU - Kempermann, Gerd
AU - Reichmann, Heinz
AU - Chrousos, George P.
AU - Licinio, Julio
AU - Wong, Ma Li
AU - Schally, Andrew V.
AU - Straube, Richard
PY - 2019/1/1
Y1 - 2019/1/1
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85074606485&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85074606485&partnerID=8YFLogxK
U2 - 10.1038/s41380-019-0542-x
DO - 10.1038/s41380-019-0542-x
M3 - Article
C2 - 31595035
AN - SCOPUS:85074606485
JO - Molecular Psychiatry
JF - Molecular Psychiatry
SN - 1359-4184
ER -