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alpha-synuclein-lip...
alpha-synuclein-lipoprotein interactions and elevated ApoE level in cerebrospinal fluid from Parkinson's disease patients
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- Paslawski, Wojciech (author)
- Karolinska Institutet
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- Zareba-Paslawska, Justyna (author)
- Karolinska Institutet
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- Zhang, Xiaoqun (author)
- Karolinska Institutet
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- Holzl, Katharina (author)
- Karolinska Institutet
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- Wadensten, Henrik (author)
- Uppsala University,Uppsala universitet,Institutionen för farmaceutisk biovetenskap,Science for Life Laboratory, SciLifeLab
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- Shariatgorji, Mohammadreza (author)
- Uppsala University,Uppsala universitet,Institutionen för farmaceutisk biovetenskap,Science for Life Laboratory, SciLifeLab
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- Janelidze, Shorena (author)
- Lund University,Lunds universitet,Klinisk minnesforskning,Forskargrupper vid Lunds universitet,Clinical Memory Research,Lund University Research Groups
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- Hansson, Oskar (author)
- Lund University,Lunds universitet,Klinisk minnesforskning,Forskargrupper vid Lunds universitet,Clinical Memory Research,Lund University Research Groups,Skåne University Hospital
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- Forsgren, Lars (author)
- Umeå University,Umeå universitet,Klinisk neurovetenskap,Umea Univ, Dept Pharmacol & Clin Neurosci, S-90187 Umea, Sweden
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- Andrén, Per E. (author)
- Uppsala University,Uppsala universitet,Institutionen för farmaceutisk biovetenskap,Science for Life Laboratory, SciLifeLab
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- Svenningsson, Per (author)
- Karolinska Institutet
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(creator_code:org_t)
- 2019-07-03
- 2019
- English.
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In: Proceedings of the National Academy of Sciences of the United States of America. - : NATL ACAD SCIENCES. - 0027-8424 .- 1091-6490. ; 116:30, s. 15226-15235
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Abstract
Subject headings
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- The progressive accumulation, aggregation, and spread of alpha-synuclein (alpha SN) are common hallmarks of Parkinson's disease (PD) pathology. Moreover, numerous proteins interact with alpha SN species, influencing its toxicity in the brain. In the present study, we extended analyses of alpha SN-interacting proteins to cerebrospinal fluid (CSF). Using coimmunoprecipitation, followed by mass spectrometry, we found that alpha SN colocalize with apolipoproteins on lipoprotein vesicles. We confirmed these interactions using several methods, including the enrichment of lipoproteins with a recombinant alpha SN, and the subsequent uptake of prepared vesicles by human dopaminergic neuronal-like cells. Further, we report an increased level of ApoE in CSF from early PD patients compared with matched controls in 3 independent cohorts. Moreover, in contrast to controls, we observed the presence of ApoE-positive neuromelanin-containing dopaminergic neurons in substantia nigra of PD patients. In conclusion, the cooccurrence of alpha SN on lipoprotein vesicles, and their uptake by dopaminergic neurons along with an increase of ApoE in early PD, proposes a mechanism(s) for alpha SN spreading in the extracellular milieu of PD.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Neurologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Neurology (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Neurovetenskaper (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Neurosciences (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Klinisk laboratoriemedicin (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Clinical Laboratory Medicine (hsv//eng)
Keyword
- apolipoproteins
- alpha-synuclein
- Parkinson's disease
- cerebrospinal fluid
- Apolipoproteins
- Cerebrospinal fluid
- Parkinson’s disease
- α-synuclein
Publication and Content Type
- ref (subject category)
- art (subject category)
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Paslawski, Wojci ...
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Zareba-Paslawska ...
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Zhang, Xiaoqun
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Holzl, Katharina
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Wadensten, Henri ...
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Shariatgorji, Mo ...
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show more...
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Janelidze, Shore ...
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Hansson, Oskar
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Forsgren, Lars
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Andrén, Per E.
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Svenningsson, Pe ...
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Clinical Medicin ...
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and Neurology
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MEDICAL AND HEAL ...
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and Basic Medicine
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and Neurosciences
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Clinical Medicin ...
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and Clinical Laborat ...
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Proceedings of t ...
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Uppsala University
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Umeå University
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Lund University
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Karolinska Institutet