Parkinson's Progression Markers Initiative Archive

Symptom frequency and mean scores over 7 years were determined. At baseline, greater SCOPA-AUT total score was associated with lower UPSIT scores (r = −0.209, p = 0.006) and with greater total MDS-UDPRS III score (r = 0.218, p = 0.004).

Clinically relevant milestones occur frequently, even in early PD. Milestones were significantly associated with baseline clinical and biological markers, but not with symptomatic treatment. Further studies are necessary to validate these results, further assess the stability of milestones, and explore translating them into an outcome measure suitable for observational and therapeutic studies.

The study provides preliminary evidence that alterations in the dopamine system predict the development of clinically-relevant, cognitive impairment in Parkinson’s disease. If replicated and determined to be causative, they demonstrate that the dopamine system is instrumental to cognitive health status throughout the disease course.

These data support the utility of BMP as a target modulation biomarker in therapeutic trials of genetic and sPD but not as a prognostic or disease progression biomarker.

The objective was to develop updated percentiles, based on substantially larger samples than previous norms, to more finely discriminate age- and sex-specific University of Pennsylvania Smell Identification Test (UPSIT) performance among ≥50-year-old adults who may be candidates for studies of prodromal neurodegenerative diseases.

Our results demonstrate that the assay classifies PD patients with high sensitivity and specificity, provides information about molecular heterogeneity, and detects prodromal individuals prior to diagnosis. These findings suggest a crucial role for αSyn-SAA in therapeutic development, both to identify pathologically defined subgroups of PD patients and to establish biomarker-defined at-risk cohorts.

Published: This paper sought to assess a Lewy body dementia case control cohort for pathogenic variants in GRN and identify mutations among patients.

Published: This paper examines the role of heterozygous Parkin mutations in three large independent case control cohorts.  

Published: This paper explores the role of the Y chromosome in PD by analyzing whole genome sequencing data from multiple sources.

Published: In this paper, the authors linked multiple homozygous loss-of-function mutations in the endocannabinoid 2-AG synthase diacylglcerol lipase beta (DAGLB) to early onset autosomal recessive PD using genetic knockdown and pharmacological inhibition of 2-AG in substantia nigra dopaminergic neurons.  

Published: NUS1 was recently associated with PD in the Chinese population. Here, the authors used large-scale PD case-control cohorts to assess NUS1 variants in individuals of European ancestry.

Published: This paper examines the H1 haplotype of the MAPT 17q.21.31 locus to better understand its contribution to PD. The authors found three novel H1 sub-haplotype blocks across the 17q.21.31 locus that is associated with PD risk.  

Published: The authors explored the molecular roles of alpha-synuclein and found that it directly modulates processing bodies (P-bodies), organelles that are involved in mRNA turnover and storage.

Published: In this paper, the authors completed a comprehensive assessment of Parkin mutations at population-scale to understand the prevalence of heterozygous Parkin mutations.  

Published: In this paper, the authors sought to find transcriptome-wide biomarkers in blood that could predict cognitive decline and identify PD patients at risk of developing cognitive impairments. Using transcriptome-wide longitudinal gene expression modeling analysis, they identified blood-based five transcripts associated with cognitive decline.

Preprint: The authors analyzed cerebrospinal fluid and plasma from Alzheimer's patients using various assays to understand which protein markers in these biofluids may be reliable biomarkers for AD pathophysiology.  

Preprint: The authors aimed to investigate the genetic etiology of dystonia-parkinsonism through examining individuals with DAT SPECT scans without evidence of dopamine defects (SWEDD). They found pathogenic variants in parkinsonian-dystonia genes occurred in more than 10% of SWEDD individuals.

Published: This article assessed an established biomarker panel, validated in Alzheimer’s Disease, in a PD cohort.

Published: This study aimed to quantifiy multiple metabolites in CSF from PD versus healthy control subjects (HCs), including longitudinal analysis.

Published: This article uses an optimized high-throughput αS-SAA (based on a previously described α-Syn protein misfolding cyclic amplification (PMCA) assay)2, 5, 6 that detects αSyn aggregates in CSF, to evaluate 140 blinded samples from the Parkinson's Progression Markers Initiative (PPMI).