O1-7-4-1Genome-wide association study identifies common variants at four loci as genetic risk factors for Parkinson's disease

There is no well-established in vivo marker of nigral degeneration in Parkinson's disease (PD) An ideal imaging marker would directly mirror the loss of substantia nigra dopaminergic neurones, which is most prominent in sub-regions called nigrosomes High-resolution, iron-sensitive, magnetic resonance imaging (MRI) at 7T allows direct nigrosome-1 visualisation in healthy people but not in PD Here, we investigated the feasibility of nigrosome-1 detection using 3T - susceptibility-weighted (SWI) MRI and the diagnostic accuracy that can be achieved for diagnosing PD in a clinical population 114 high-resolution 3T – SWI-scans were reviewed consisting of a prospective case-control study in 19 subjects (10 PD, 9 controls) and a retrospective cross-sectional study in 95 consecutive patients undergoing routine clinical SWI-scans (>50 years, 9 PD, 81 non-PD, 5 non-diagnostic studies excluded) Two raters independently classified subjects into PD and non-PD according to absence or presence of nigrosome-1, followed by consensus reading Diagnostic accuracy was assessed against clinical diagnosis as gold standard Absolute inter- and intra-rater agreement was ≥94% (kappa≥082, p<0001) In the prospective study 8/9 control and 8/10 PD; and in the retrospective study 77/81 non-PD and all 9 PD subjects were correctly classified Diagnostic accuracy of the retrospective cohort was: sensitivity 100%, specificity 95%, NPV 1, PPV 069 and accuracy 96% which dropped to 91% when including non-diagnostic scans (‘intent to diagnose’) The healthy nigrosome-1 can be readily depicted on high-resolution 3T - SWI giving rise to a ‘swallow tail’ appearance of the dorsolateral substantia nigra, and this feature is lost in PD Visual radiological assessment yielded a high diagnostic accuracy for PD vs an unselected clinical control population Assessing the substantia nigra on SWI for the typical ‘swallow tail’ appearance has potential to become a new and easy applicable 3T MRI diagnostic tool for nigral degeneration in PD

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The 'swallow tail' appearance of the healthy nigrosome - a new accurate test of Parkinson's disease: a case-control and retrospective cross-sectional MRI study at 3T

Parkinson's disease (PD) is a common neurodegenerative disorder, characterized pathologically by the presence of α-synuclein (α-syn)-rich Lewy bodies. As clinical diagnosis of PD is challenging, misdiagnosis is common, highlighting the need for disease-specific and early stage biomarkers. Both early diagnosis of PD and adequate tracking of disease progression could significantly improve outcomes for patients, particularly in regard to existing and future disease modifying treatments. Given its critical roles in PD pathogenesis, α-syn may be useful as a biomarker of PD. The aim of this review is, therefore, to summarize the efficacy of tissue and body fluid α-syn measurements in the detection of PD as well as monitoring disease progression. In comparison to solid tissue specimens and biopsies, biofluid α-syn levels may be the most promising candidates in PD diagnosis and progression based on specificity, sensitivity and availability. Although α-syn has been tested most extensively in cerebrospinal fluid (CSF), the relatively invasive procedure for collecting CSF is not suitable in most clinical settings, leading to investigation of plasma, blood and saliva as alternatives. The exploration of combined biomarkers, along with α-syn, to improve diagnostic accuracy is also likely required.

Alpha-Synuclein as a Biomarker for Parkinson's Disease.

Progression of Parkinson’s disease (PD) is highly variable, indicating that differences between slow and rapid progression forms could provide valuable information for improved early detection and management Unfortunately, this represents a complex problem due to the heterogeneous nature of humans in regards to demographic characteristics, genetics, diet, environmental exposures and health behaviors In this pilot study, we employed high resolution mass spectrometry-based metabolic profiling to investigate the metabolic signatures of slow versus rapidly progressing PD present in human serum Archival serum samples from PD patients obtained within 3 years of disease onset were analyzed via dual chromatography-high resolution mass spectrometry, with data extraction by xMSanalyzer and used to predict rapid or slow motor progression of these patients during follow-up Statistical analyses, such as false discovery rate analysis and partial least squares discriminant analysis, yielded a list of statistically significant metabolic features and further investigation revealed potential biomarkers In particular, N8-acetyl spermidine was found to be significantly elevated in the rapid progressors compared to both control subjects and slow progressors Our exploratory data indicate that a fast motor progression disease phenotype can be distinguished early in disease using high resolution mass spectrometry-based metabolic profiling and that altered polyamine metabolism may be a predictive marker of rapidly progressing PD

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Serum metabolomics of slow vs. rapid motor progression Parkinson's disease: a pilot study.

This study followed 89 patients with Parkinson disease (PD) who had either normal sleep without hallucinations, sleep fragmentation only, vivid dreams/nightmares, hallucinations with insight, or hallucinations without insight. The increasing prevalence and progressive severity of hallucinations followed a different pattern of progression from sleep disorders; though sleep aberrations were common in those with hallucinations, sleep problems did not predict hallucinations in PD.

Chuantao Zuo

Papers

Biomarkers of Parkinson's disease: current status and future perspectives.

Biomarkers of Parkinson's disease