Contactin-1 Is Reduced in Cerebrospinal Fluid of Parkinson's Disease Patients and Is Present within Lewy Bodies

Biomolecules. 2020 Aug 12;10(8):1177. doi: 10.3390/biom10081177.


Synaptic degeneration is an early phenomenon in Parkinson's disease (PD) pathogenesis. We aimed to investigate whether levels of synaptic proteins contactin-1 and contactin-2 in cerebrospinal fluid (CSF) of PD patients are reduced compared to dementia with Lewy bodies (DLB) patients and controls and to evaluate their relationship with α-synuclein aggregation. Contactin-1 and -2 were measured in CSF from PD patients (n = 58), DLB patients (n = 72) and age-matched controls (n = 90). Contactin concentration differences between diagnostic groups were assessed by general linear models adjusted for age and sex. Contactin immunoreactivity was characterized in postmortem substantia nigra, hippocampus and entorhinal cortex tissue of PD patients (n = 4) and controls (n = 4), and its relation to α-syn aggregation was evaluated using confocal laser scanning microscopy. Contactin-1 levels were lower in PD patients (42 (36-49) pg/mL) compared to controls (52 (44-58) pg/mL, p = 0.003) and DLB patients (56 (46-67) pg/mL, p = 0.001). Contactin-2 levels were similar across all diagnostic groups. Within the PD patient group, contactin-1 correlated with t-α-syn, tTau and pTau (r = 0.30-0.50, p < 0.05), whereas contactin-2 only correlated with t-α-syn (r = 0.34, p = 0.03). Contactin-1 and -2 were observed within nigral and cortical Lewy bodies and clustered within bulgy Lewy neurites in PD brains. A decrease in CSF contactin-1 may reflect synaptic degeneration underlying Lewy body pathology in PD.

Keywords: Lewy bodies; Parkinson’s disease (PD); biomarker; cerebrospinal fluid (CSF); contactin; dementia with Lewy bodies (DLB); synaptic degeneration.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Autopsy
  • Case-Control Studies
  • Contactin 1 / cerebrospinal fluid*
  • Contactin 2 / metabolism*
  • Down-Regulation*
  • Entorhinal Cortex / metabolism
  • Female
  • Hippocampus / metabolism
  • Humans
  • Lewy Body Disease / cerebrospinal fluid
  • Lewy Body Disease / metabolism*
  • Linear Models
  • Male
  • Middle Aged
  • Parkinson Disease / cerebrospinal fluid
  • Parkinson Disease / metabolism*
  • Protein Aggregates
  • Substantia Nigra / metabolism
  • alpha-Synuclein / metabolism
  • tau Proteins / metabolism


  • CNTN1 protein, human
  • CNTN2 protein, human
  • Contactin 1
  • Contactin 2
  • MAPT protein, human
  • Protein Aggregates
  • alpha-Synuclein
  • tau Proteins