GPNMB Biomarker Levels in GBA1 Carriers with Lewy Body Disorders.

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.

Testing for Allele-specific Expression from Human Brain Samples.

Many single nucleotide polymorphisms (SNPs) identified by genome-wide association studies exert their effects on disease risk as expression quantitative trait loci (eQTL) via allele-specific expression (ASE). While databases for probing eQTLs in tissues from normal individuals exist, one may wish to ascertain eQTLs or ASE in specific tissues or disease-states not characterized in these databases. Here, we present a protocol to assess ASE of two possible target genes (GPNMB and KLHL7) of a known genome-wide association study (GWAS) Parkinson's disease (PD) risk locus in postmortem human brain tissue from PD and neurologically normal individuals.

GPNMB confers risk for Parkinson's disease through interaction with α-synuclein.

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).

Abnormal B-Cell and Tfh-Cell Profiles in Patients With Parkinson Disease: A Cross-sectional Study.

Background And Objectives: There has been growing interest in potential roles of the immune system in the pathogenesis of Parkinson disease (PD). The aim of the current study was to comprehensively characterize phenotypic and functional profiles of circulating immune cells in patients with PD vs controls.

Methods: Peripheral blood was collected from patients with PD and age- and sex-matched neurologically normal controls (NCs) in 2 independent cohorts (discovery and validation).

Regional Brain Recovery from Acute Synaptic Injury in Simian Immunodeficiency Virus-Infected Rhesus Macaques Associates with Heme Oxygenase Isoform Expression.

Brain injury occurs within days in simian immunodeficiency virus (SIV) or human immunodeficiency virus (HIV) infection, and some recovery may occur within weeks. Inflammation and oxidative stress associate with such injury, but what drives recovery is unknown. Chronic HIV infection associates with reduced brain frontal cortex expression of the antioxidant/anti-inflammatory enzyme heme oxygenase-1 (HO-1) and increased neuroinflammation in individuals with cognitive impairment.

Omics in Neurodegenerative Disease: Hope or Hype?

The past 15 years have seen a boom in the use and integration of 'omic' approaches (limited here to genomic, transcriptomic, and epigenomic techniques) to study neurodegenerative disease in an unprecedented way. We first highlight advances in and the limitations of using such approaches in the neurodegenerative disease literature, with a focus on Alzheimer's disease (AD), Parkinson's disease (PD), frontotemporal lobar degeneration (FTLD), and amyotrophic lateral sclerosis (ALS). We next discuss how these studies can advance human health in the form of generating leads for downstream mechanistic investigation or yielding polygenic risk scores (PRSs) for prognostication.