Publications by authors named "Skrinak R"

Aggregation of misfolded α-synuclein (aSyn) within the brain is the pathologic hallmark of Lewy body diseases (LBD), including Parkinson's disease (PD) and dementia with Lewy bodies (DLB). Evidence exists for aSyn "strains" - conformations with distinct biological properties. However, biomarkers for PD vs.

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Spread and aggregation of misfolded α-synuclein (aSyn) within the brain is the pathologic hallmark of Lewy body diseases (LBD), including Parkinson's disease (PD) and dementia with Lewy bodies (DLB). While evidence exists for multiple aSyn protein conformations, often termed "strains" for their distinct biological properties, it is unclear whether PD and DLB result from aSyn strain differences, and biomarkers that differentiate PD and DLB are lacking. Moreover, while pathological forms of aSyn have been detected outside the brain ( in skin, gut, blood), the functional significance of these peripheral aSyn species is unclear.

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Background: The GPNMB single-nucleotide polymorphism rs199347 and GBA1 variants both associate with Lewy body disorder (LBD) risk. GPNMB encodes glycoprotein nonmetastatic melanoma protein B (GPNMB), a biomarker for GBA1-associated Gaucher's disease.

Objective: The aim of this study was to determine whether GPNMB levels (1) differ in LBD with and without GBA1 variants and (2) associate with rs199347 genotype.

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Many risk loci for Parkinson's disease (PD) have been identified by genome-wide association studies (GWASs), but target genes and mechanisms remain largely unknown. We linked the GWAS-derived chromosome 7 locus (sentinel single-nucleotide polymorphism rs199347) to through colocalization analyses of expression quantitative trait locus and PD risk signals, confirmed by allele-specific expression studies in the human brain. In cells, glycoprotein nonmetastatic melanoma protein B (GPNMB) coimmunoprecipitated and colocalized with α-synuclein (aSyn).

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Objective: Using a multi-cohort, discovery-replication-validation design, we sought new plasma biomarkers that predict which individuals with Parkinson's disease (PD) will experience cognitive decline.

Methods: In 108 discovery cohort PD individuals and 83 replication cohort PD individuals, we measured 940 plasma proteins on an aptamer-based platform. Using proteins associated with subsequent cognitive decline in both cohorts, we trained a logistic regression model to predict which patients with PD showed fast (> = 1 point drop/year on Montreal Cognitive Assessment [MoCA]) versus slow (< 1 point drop/year on MoCA) cognitive decline in the discovery cohort, testing it in the replication cohort.

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Article Synopsis
  • Parkinson's disease (PD) is a common neurodegenerative condition with around 5 million affected globally, and current treatments don’t modify the disease; researchers aimed to identify blood biomarkers to better diagnose and predict PD progression.
  • The study utilized plasma samples from two groups—96 participants with PD and 45 healthy controls—analyzing over 1,000 proteins to identify potential biomarkers by comparing protein levels across groups while considering factors like age and sex.
  • Four biomarkers were significantly linked to PD and confirmed in a larger follow-up study, including bone sialoprotein (BSP) and osteomodulin (OMD), reinforcing their potential as useful indicators for the disease.
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