Correlated levels of cerebrospinal fluid pathogenic proteins in drug-naïve Parkinson's disease

Hidetomo Murakami, Takahiko Tokuda, Omar Ali El-Agnaf, Takuma Ohmichi, Ayako Miki, Hideaki Ohashi, Yoshiyuki Owan, Yu Saito, Satoshi Yano, Tamao Tsukie, Takeshi Ikeuchi, Kenjiro Ono

Research output: Contribution to journalArticle

Abstract

Background and aim: Toxic oligomeric α-synuclein (αS; O-αS) has been suggested to play a central role in the pathogenesis of Lewy body diseases such as Parkinson's disease (PD). Cerebrospinal fluid (CSF) levels of αS, O-αS, total and phosphorylated tau, and amyloid β 1-42 (Aβ1-42) are thought to reflect the pathophysiology or clinical symptoms in PD. In this study, we examined correlations of the CSF levels of these proteins with the clinical symptoms, and with each other in drug-naïve patients with PD. Methods: Twenty-seven drug-naïve patients with PD were included. Motor and cognitive functions were assessed using the Unified Parkinson's Disease Rating Scale (UPDRS), Montreal Cognitive Assessment (MoCA), and Neurobehavioral Cognitive Status Examination (COGNISTAT). CSF levels of total αS, O-αS, Aβ1-42, total tau and tau phosphorylated at threonine 181 (P-tau181p) were measured. CSF levels of these proteins were compared with clinical assessments from the UPDRS, MoCA and COGNISTAT using Spearman correlation analysis. Spearman correlation coefficients among CSF protein levels were also evaluated. Results: CSF levels of αS were negatively correlated with UPDRS part III (motor score) (p < 0.05) and bradykinesia (p < 0.01), and positively correlated with COGNISTAT subtest of judgement (p < 0.01) and CSF levels of Aβ1-42 (p < 0.001), total tau (p < 0.001) and P-tau181p (p < 0.01). Lower CSF levels of Aβ1-42, total tau and P-tau181p were significantly related to worsening of some motor and/or cognitive functions. The CSF level of O-αS showed no correlation with any motor and cognitive assessments or with CSF levels of the other proteins. Conclusion: CSF levels of αS are correlated with some clinical symptoms and CSF levels of other pathogenic proteins in drug-naïve PD patients. These correlations suggest a central role for interaction and aggregation of αS with Aβ1-42, tau, and phosphorylated tau in the pathogenesis of PD. Although O-αS has been shown to have neurotoxic effects, CSF levels do not reflect clinical symptoms or levels of other proteins in cross-sectional assessment.

Original languageEnglish
Article number113
JournalBMC Neurology
Volume19
Issue number1
DOIs
Publication statusPublished - 4 Jun 2019

Fingerprint

Cerebrospinal Fluid Proteins
Parkinson Disease
Cerebrospinal Fluid
Amyloid
Pharmaceutical Preparations
Cognition
Synucleins
Lewy Body Disease
Hypokinesia
Proteins
Poisons
Threonine

Keywords

  • Amyloid β-protein (1-42)
  • Clinical symptom
  • Oligomer
  • Parkinson's disease
  • Tau protein
  • α-Synuclein

ASJC Scopus subject areas

  • Clinical Neurology

Cite this

Correlated levels of cerebrospinal fluid pathogenic proteins in drug-naïve Parkinson's disease. / Murakami, Hidetomo; Tokuda, Takahiko; Ali El-Agnaf, Omar; Ohmichi, Takuma; Miki, Ayako; Ohashi, Hideaki; Owan, Yoshiyuki; Saito, Yu; Yano, Satoshi; Tsukie, Tamao; Ikeuchi, Takeshi; Ono, Kenjiro.

In: BMC Neurology, Vol. 19, No. 1, 113, 04.06.2019.

Research output: Contribution to journalArticle

Murakami, H, Tokuda, T, Ali El-Agnaf, O, Ohmichi, T, Miki, A, Ohashi, H, Owan, Y, Saito, Y, Yano, S, Tsukie, T, Ikeuchi, T & Ono, K 2019, 'Correlated levels of cerebrospinal fluid pathogenic proteins in drug-naïve Parkinson's disease', BMC Neurology, vol. 19, no. 1, 113. https://doi.org/10.1186/s12883-019-1346-y
Murakami, Hidetomo ; Tokuda, Takahiko ; Ali El-Agnaf, Omar ; Ohmichi, Takuma ; Miki, Ayako ; Ohashi, Hideaki ; Owan, Yoshiyuki ; Saito, Yu ; Yano, Satoshi ; Tsukie, Tamao ; Ikeuchi, Takeshi ; Ono, Kenjiro. / Correlated levels of cerebrospinal fluid pathogenic proteins in drug-naïve Parkinson's disease. In: BMC Neurology. 2019 ; Vol. 19, No. 1.
@article{010d5c09077e49fa8fa01f4c9773c635,
title = "Correlated levels of cerebrospinal fluid pathogenic proteins in drug-na{\"i}ve Parkinson's disease",
abstract = "Background and aim: Toxic oligomeric α-synuclein (αS; O-αS) has been suggested to play a central role in the pathogenesis of Lewy body diseases such as Parkinson's disease (PD). Cerebrospinal fluid (CSF) levels of αS, O-αS, total and phosphorylated tau, and amyloid β 1-42 (Aβ1-42) are thought to reflect the pathophysiology or clinical symptoms in PD. In this study, we examined correlations of the CSF levels of these proteins with the clinical symptoms, and with each other in drug-na{\"i}ve patients with PD. Methods: Twenty-seven drug-na{\"i}ve patients with PD were included. Motor and cognitive functions were assessed using the Unified Parkinson's Disease Rating Scale (UPDRS), Montreal Cognitive Assessment (MoCA), and Neurobehavioral Cognitive Status Examination (COGNISTAT). CSF levels of total αS, O-αS, Aβ1-42, total tau and tau phosphorylated at threonine 181 (P-tau181p) were measured. CSF levels of these proteins were compared with clinical assessments from the UPDRS, MoCA and COGNISTAT using Spearman correlation analysis. Spearman correlation coefficients among CSF protein levels were also evaluated. Results: CSF levels of αS were negatively correlated with UPDRS part III (motor score) (p < 0.05) and bradykinesia (p < 0.01), and positively correlated with COGNISTAT subtest of judgement (p < 0.01) and CSF levels of Aβ1-42 (p < 0.001), total tau (p < 0.001) and P-tau181p (p < 0.01). Lower CSF levels of Aβ1-42, total tau and P-tau181p were significantly related to worsening of some motor and/or cognitive functions. The CSF level of O-αS showed no correlation with any motor and cognitive assessments or with CSF levels of the other proteins. Conclusion: CSF levels of αS are correlated with some clinical symptoms and CSF levels of other pathogenic proteins in drug-na{\"i}ve PD patients. These correlations suggest a central role for interaction and aggregation of αS with Aβ1-42, tau, and phosphorylated tau in the pathogenesis of PD. Although O-αS has been shown to have neurotoxic effects, CSF levels do not reflect clinical symptoms or levels of other proteins in cross-sectional assessment.",
keywords = "Amyloid β-protein (1-42), Clinical symptom, Oligomer, Parkinson's disease, Tau protein, α-Synuclein",
author = "Hidetomo Murakami and Takahiko Tokuda and {Ali El-Agnaf}, Omar and Takuma Ohmichi and Ayako Miki and Hideaki Ohashi and Yoshiyuki Owan and Yu Saito and Satoshi Yano and Tamao Tsukie and Takeshi Ikeuchi and Kenjiro Ono",
year = "2019",
month = "6",
day = "4",
doi = "10.1186/s12883-019-1346-y",
language = "English",
volume = "19",
journal = "BMC Neurology",
issn = "1471-2377",
publisher = "BioMed Central",
number = "1",

}

TY - JOUR

T1 - Correlated levels of cerebrospinal fluid pathogenic proteins in drug-naïve Parkinson's disease

AU - Murakami, Hidetomo

AU - Tokuda, Takahiko

AU - Ali El-Agnaf, Omar

AU - Ohmichi, Takuma

AU - Miki, Ayako

AU - Ohashi, Hideaki

AU - Owan, Yoshiyuki

AU - Saito, Yu

AU - Yano, Satoshi

AU - Tsukie, Tamao

AU - Ikeuchi, Takeshi

AU - Ono, Kenjiro

PY - 2019/6/4

Y1 - 2019/6/4

N2 - Background and aim: Toxic oligomeric α-synuclein (αS; O-αS) has been suggested to play a central role in the pathogenesis of Lewy body diseases such as Parkinson's disease (PD). Cerebrospinal fluid (CSF) levels of αS, O-αS, total and phosphorylated tau, and amyloid β 1-42 (Aβ1-42) are thought to reflect the pathophysiology or clinical symptoms in PD. In this study, we examined correlations of the CSF levels of these proteins with the clinical symptoms, and with each other in drug-naïve patients with PD. Methods: Twenty-seven drug-naïve patients with PD were included. Motor and cognitive functions were assessed using the Unified Parkinson's Disease Rating Scale (UPDRS), Montreal Cognitive Assessment (MoCA), and Neurobehavioral Cognitive Status Examination (COGNISTAT). CSF levels of total αS, O-αS, Aβ1-42, total tau and tau phosphorylated at threonine 181 (P-tau181p) were measured. CSF levels of these proteins were compared with clinical assessments from the UPDRS, MoCA and COGNISTAT using Spearman correlation analysis. Spearman correlation coefficients among CSF protein levels were also evaluated. Results: CSF levels of αS were negatively correlated with UPDRS part III (motor score) (p < 0.05) and bradykinesia (p < 0.01), and positively correlated with COGNISTAT subtest of judgement (p < 0.01) and CSF levels of Aβ1-42 (p < 0.001), total tau (p < 0.001) and P-tau181p (p < 0.01). Lower CSF levels of Aβ1-42, total tau and P-tau181p were significantly related to worsening of some motor and/or cognitive functions. The CSF level of O-αS showed no correlation with any motor and cognitive assessments or with CSF levels of the other proteins. Conclusion: CSF levels of αS are correlated with some clinical symptoms and CSF levels of other pathogenic proteins in drug-naïve PD patients. These correlations suggest a central role for interaction and aggregation of αS with Aβ1-42, tau, and phosphorylated tau in the pathogenesis of PD. Although O-αS has been shown to have neurotoxic effects, CSF levels do not reflect clinical symptoms or levels of other proteins in cross-sectional assessment.

AB - Background and aim: Toxic oligomeric α-synuclein (αS; O-αS) has been suggested to play a central role in the pathogenesis of Lewy body diseases such as Parkinson's disease (PD). Cerebrospinal fluid (CSF) levels of αS, O-αS, total and phosphorylated tau, and amyloid β 1-42 (Aβ1-42) are thought to reflect the pathophysiology or clinical symptoms in PD. In this study, we examined correlations of the CSF levels of these proteins with the clinical symptoms, and with each other in drug-naïve patients with PD. Methods: Twenty-seven drug-naïve patients with PD were included. Motor and cognitive functions were assessed using the Unified Parkinson's Disease Rating Scale (UPDRS), Montreal Cognitive Assessment (MoCA), and Neurobehavioral Cognitive Status Examination (COGNISTAT). CSF levels of total αS, O-αS, Aβ1-42, total tau and tau phosphorylated at threonine 181 (P-tau181p) were measured. CSF levels of these proteins were compared with clinical assessments from the UPDRS, MoCA and COGNISTAT using Spearman correlation analysis. Spearman correlation coefficients among CSF protein levels were also evaluated. Results: CSF levels of αS were negatively correlated with UPDRS part III (motor score) (p < 0.05) and bradykinesia (p < 0.01), and positively correlated with COGNISTAT subtest of judgement (p < 0.01) and CSF levels of Aβ1-42 (p < 0.001), total tau (p < 0.001) and P-tau181p (p < 0.01). Lower CSF levels of Aβ1-42, total tau and P-tau181p were significantly related to worsening of some motor and/or cognitive functions. The CSF level of O-αS showed no correlation with any motor and cognitive assessments or with CSF levels of the other proteins. Conclusion: CSF levels of αS are correlated with some clinical symptoms and CSF levels of other pathogenic proteins in drug-naïve PD patients. These correlations suggest a central role for interaction and aggregation of αS with Aβ1-42, tau, and phosphorylated tau in the pathogenesis of PD. Although O-αS has been shown to have neurotoxic effects, CSF levels do not reflect clinical symptoms or levels of other proteins in cross-sectional assessment.

KW - Amyloid β-protein (1-42)

KW - Clinical symptom

KW - Oligomer

KW - Parkinson's disease

KW - Tau protein

KW - α-Synuclein

UR - http://www.scopus.com/inward/record.url?scp=85066870623&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85066870623&partnerID=8YFLogxK

U2 - 10.1186/s12883-019-1346-y

DO - 10.1186/s12883-019-1346-y

M3 - Article

VL - 19

JO - BMC Neurology

JF - BMC Neurology

SN - 1471-2377

IS - 1

M1 - 113

ER -