α-synuclein−lipoprotein interactions and elevated ApoE level in cerebrospinal fluid from Parkinson’s disease patients

Forskningsoutput: TidskriftsbidragArtikel i vetenskaplig tidskrift

Abstract

The progressive accumulation, aggregation, and spread of α-synuclein (αSN) are common hallmarks of Parkinson’s disease (PD) pathology. Moreover, numerous proteins interact with αSN species, influencing its toxicity in the brain. In the present study, we extended analyses of αSN-interacting proteins to cerebrospinal fluid (CSF). Using coimmunoprecipitation, followed by mass spectrometry, we found that αSN colocalize with apolipoproteins on lipoprotein vesicles. We confirmed these interactions using several methods, including the enrichment of lipoproteins with a recombinant αSN, 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 αSN on lipoprotein vesicles, and their uptake by dopaminergic neurons along with an increase of ApoE in early PD, proposes a mechanism(s) for αSN spreading in the extracellular milieu of PD.

Detaljer

Författare
  • Wojciech Paslawski
  • Justyna Zareba-Paslawska
  • Xiaoqun Zhang
  • Katharina Hölzl
  • Henrik Wadensten
  • Mohammadreza Shariatgorji
  • Shorena Janelidze
  • Oskar Hansson
  • Lars Forsgren
  • Per E. Andrén
  • Per Svenningsson
Enheter & grupper
Externa organisationer
  • Karolinska Institute
  • Uppsala universitet, Historiska institutionen
  • Skåne University Hospital
  • Umeå University
Forskningsområden

Ämnesklassifikation (UKÄ) – OBLIGATORISK

  • Neurologi

Nyckelord

Originalspråkengelska
Sidor (från-till)15226-15235
Antal sidor10
TidskriftProceedings of the National Academy of Sciences of the United States of America
Volym116
Utgivningsnummer30
StatusPublished - 2019 jul 23
PublikationskategoriForskning
Peer review utfördJa