Strong Predictive Algorithm of Pathogenesis-Based Biomarkers Improves Parkinson’s Disease Diagnosis

Easily accessible and accurate biomarkers can aid Parkinson’s disease diagnosis. We investigated whether combining plasma levels of α-synuclein, anti-α-synuclein, and/or their ratios to amyloid beta-40 correlated with clinical diagnosis. The inclusion of amyloid beta-40 (Aβ40) is novel. Plasma level...

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Vydané v:Molecular neurobiology Ročník 59; číslo 3; s. 1476 - 1485
Hlavní autori: Chan, Daniel Kam Yin, Braidy, Nady, Chen, Ren Fen, Xu, Ying Hua, Bentley, Steven, Lubomski, Michal, Davis, Ryan L., Chen, Jack, Sue, Carolyn M., Mellick, George D.
Médium: Journal Article
Jazyk:English
Vydavateľské údaje: New York Springer US 01.03.2022
Springer Nature B.V
Predmet:
Adult
Aged
Aged, 80 and over
Algorithms
alpha-Synuclein
Amyloid beta-Peptides
Biomarkers
Biomedical and Life Sciences
Biomedicine
Cell Biology
Diagnosis
Female
Humans
Male
Medical diagnosis
Middle Aged
Movement disorders
Neurobiology
Neurodegenerative diseases
Neurology
Neurosciences
Parkinson Disease - diagnosis
Parkinson's disease
Pathogenesis
Plasma levels
ROC Curve
Synuclein
Biomarkers
Amyloid-beta40
Diagnosis
Parkinson’s disease
Alpha-synuclein
ISSN:0893-7648, 1559-1182, 1559-1182
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Shrnutí:Easily accessible and accurate biomarkers can aid Parkinson’s disease diagnosis. We investigated whether combining plasma levels of α-synuclein, anti-α-synuclein, and/or their ratios to amyloid beta-40 correlated with clinical diagnosis. The inclusion of amyloid beta-40 (Aβ40) is novel. Plasma levels of biomarkers were quantified with ELISA. Using receiver operating characteristic (ROC) curve analysis, levels of α-synuclein, anti-α-synuclein, and their ratios with Aβ40 were analyzed in an initial training set of cases and controls. Promising biomarkers were then used to build a diagnostic algorithm. Verification of the results of biomarkers and the algorithm was performed in an independent set. The training set consisted of 50 cases (age 65.2±9.3, range 44–83, female:male=21:29) with 50 age- and gender-matched controls (67.1±10.0, range 45–96 years; female:male=21:29). ROC curve analysis yielded the following area under the curve results: anti-α-synuclein=0.835, α-synuclein=0.738, anti-α-synuclein/Aβ40=0.737, and α-synuclein/Aβ40=0.663. A 2-step diagnostic algorithm was built: either α-synuclein or anti-α-synuclein was ≥2 times the means of controls (step-1), resulting in 74% sensitivity; and adding α-synuclein/Aβ40 or anti-α-synuclein/Aβ40 (step-2) yielded better sensitivity (82%) while using step-2 alone yielded good specificity in controls (98%). The results were verified in an independent sample of 46 cases and 126 controls, with sensitivity reaching 91.3% and specificity 90.5%. The algorithm was equally sensitive in Parkinson’s disease of ≤5-year duration with 92.6% correctly identified in the training set and 90% in the verification set. With two independent samples totaling 272 subjects, our study showed that combination of biomarkers of α-synuclein, anti-α-synuclein, and their ratios to Aβ40 showed promising sensitivity and specificity.
Bibliografia:ObjectType-Article-1
SourceType-Scholarly Journals-1
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ISSN:0893-7648
1559-1182
1559-1182
DOI:10.1007/s12035-021-02604-6