Cortical Thinning Associated with Age and CSF Biomarkers in Early Parkinson's Disease Is Modified by the SNCA rs356181 Polymorphism.

Abstract

The role of cerebrospinal fluid (CSF) biomarkers such as CSF α-synuclein and CSF tau in predicting cognitive decline in Parkinson's disease (PD) continues to be inconsistent. Here, using a cohort of de novo PD patients with preserved cognition from the Parkinson's Progression Markers Initiative (PPMI), we show that the SNCA rs356181 single nucleotide polymorphism (SNP) modulates the effect of these CSF biomarkers on cortical thinning. Depending on this SNP's genotype, cortical atrophy was associated with either higher or lower CSF biomarker levels. Additionally, this SNP modified age-related atrophy. Importantly, the integrity of the brain regions where this phenomenon was observed correlated with cognitive measures. These results suggest that this genetic variation of the gene encoding the α-synuclein protein, known to be involved in the development of PD, also interferes in its subsequent neurodegeneration. Overall, our findings could shed light on the so far incongruent association of common CSF biomarkers with cognitive decline in PD.

• Authors: Frederic Sampedro, Juan Marín-Lahoz, Saul Martínez-Horta, Javier Pagonabarraga, Jaime Kulisevsky
• Journal: Neuro-degenerative diseases (Neurodegener Dis) Vol. 18 Issue 5-6 Pg. 233-238 ( 2018) ISSN: 1660-2862 [Electronic] Switzerland
• PMID: 30336481 (Publication Type: News, Research Support, Non-U.S. Gov't)
• Copyright: © 2018 S. Karger AG, Basel.

Chemical References

• Amyloid beta-Peptides
• Biomarkers
• Peptide Fragments
• SNCA protein, human
• alpha-Synuclein
• tau Proteins

Topics

• Age Factors
• Aged
• Amyloid beta-Peptides (cerebrospinal fluid)
• Biomarkers (cerebrospinal fluid)
• Cognition (physiology)
• Early Diagnosis
• Female
• Gene Expression (genetics)
• Humans
• Male
• Middle Aged
• Parkinson Disease (cerebrospinal fluid, complications, genetics)
• Peptide Fragments (cerebrospinal fluid)
• alpha-Synuclein (cerebrospinal fluid, genetics)
• tau Proteins (cerebrospinal fluid)