There is an urgent need to find reliable and accessible blood-based biomarkers for early diagnosis of Parkinson's disease (PD) correlating with clinical symptoms and displaying predictive potential to improve future clinical trials. This led us to a conduct large-scale proteomics approach using an advanced high-throughput proteomics technology to create a proteomic profile for PD. Over 1300 proteins were measured in serum samples from a de novo Parkinson's (DeNoPa) cohort made up of 85 deep clinically phenotyped drug-naïve de novo PD patients and 93 matched healthy controls (HC) with longitudinal clinical follow-up available of up to 8 years. The analysis identified 73 differentially expressed proteins (DEPs) of which 14 proteins were confirmed as stable potential diagnostic markers using machine learning tools. Among the DEPs identified, eight proteins-ALCAM, contactin 1, CD36, DUS3, NEGR1, Notch1, TrkB, and BTK- significantly correlated with longitudinal clinical scores including motor and non-motor symptom scores, cognitive function and depression scales, indicating potential predictive values for progression in PD among various phenotypes. Known functions of these proteins and their possible relation to the pathophysiology or symptomatology of PD were discussed and presented with a particular emphasis on the potential biological mechanisms involved, such as cell adhesion, axonal guidance and neuroinflammation, and T-cell activation. In conclusion, with the use of advance multiplex proteomic technology, a blood-based protein signature profile was identified from serum samples of a well-characterized PD cohort capable of potentially differentiating PD from HC and predicting clinical disease progression of related motor and non-motor PD symptoms. We thereby highlight the need to validate and further investigate these markers in future prospective cohorts and assess their possible PD-related mechanisms.

To develop a simplified smell test for identifying patients with Parkinson’s disease (PD), we reevaluated the Sniffin’-Sticks-Identification-Test (SST-ID) and University-of-Pennsylvania-Smell-Identification-Test (UPSIT), using three case-control studies. These included 301 patients with PD or dementia with Lewy bodies (DLB), 68 subjects with multiple-system atrophy (MSA) or progressive supranuclear palsy (PSP), and 281 healthy controls (HC). Scents were ranked by area-under-the-curve values for group classification and results leveraged by 8 published studies with 5853 individuals. PD/DLB patients showed markedly worse olfaction than controls, whereas scores for MSA/PSP subjects were intermediate. We identified and validated a subset of 7 shared odorants that performed similarly to the traditional 16-scent SST-ID and 40-scent UPSIT tests in distinguishing PD/DLB from HC. There, the identification of 4 or fewer scents out of 7 served as an effective cut-off between the two groups. We also identified a critical role for distractors (from correct answers) and age on olfaction performance.

L1 cell adhesion molecule (L1CAM)-positive extracellular vesicles (EVs) are being explored as a potential source of biomarkers for Parkinson’s disease (PD) in peripheral blood. However, their utility remains controversial. In this study, we sought to investigate the proteome composition of L1CAM⁺-EVs isolated from human blood plasma and evaluate their potential as biomarkers for PD. L1CAM⁺-EVs were extracted from blood plasma using direct immunoprecipitation by employing magnetic beads coupled to an anti-L1CAM antibody. The Proximity Extension Assay platform, Olink Explore 3072, was used to analyze samples from 60 individuals: 20 healthy controls (HC), 20 patients with isolated REM sleep behavior disorder (iRBD), and 20 PD patients. Targeted proteomic analysis identified 2841 proteins in L1CAM⁺-EVs, of which 203 exhibited differential expression across groups. Although these changes were not statistically significant, after correction for multiple testing, a combination of 12 proteins could discriminate between PD and HC. Moreover, several proteins displayed trends toward upregulation or downregulation in PD and iRBD when compared with HC. These preliminary findings suggest that L1CAM⁺-EVs proteins show some potential as biomarkers for PD; however, further investigation and validation studies are required.

Background Alterations in neurofilament light chain (NfL), reflecting axonal damage, have been proposed as a biomarker for neurological disorders including Parkinson’s disease (PD). Methods We measured NfL concentrations by immunoassay in (1) a set of longitudinal CSF samples from 82 PD, 14 other neurodegenerative disorders (OND), and 53 healthy controls (HC); (2) A cross-sectional cohort with paired CSF and serum samples from subjects with 151 PD, 344 OND, and 20 HC, and (3a) a large longitudinal validation cohort with serum samples from 375 PD, 178 HC, and 57 prodromal Lewy Body disorder with hyposmia or isolated REM sleep behaviour disorder (iRBD), (3b) 216 symptomatic and 298 asymptomatic LRRK2, GBA, and SNCA mutation carriers in the Parkinson’s Progression Markers Initiative (PPMI). Mean differences in serum NfL levels between diagnostic groups, and correlation with motor signs, cognitive measures and dopamine transporter imaging, were assessed. Linear mixed effects models were used to assess longitudinal changes in log10 (NfL) in relation to demographic, clinical, and imaging variables. Findings In the longitudinal cohort (1) NfL in CSF increased over time and was significantly positively correlated with MDS-UPDRS III motor and total scores in the PD group (p=0·0231 and 0·0081). In the cross-sectional cohort (2) the paired CSF and serum NfL samples were highly correlated (Spearman’s rank ). In the large validation cohort (3a) mean baseline serum NfL was higher in PD (13 ±7·2pg/ml), hyposmics (15±15·1pg/ml), and iRBD (17±8pg/ml) compared with HC (12±6·7pg/ml) but was highest in the seven OND cases (18±7pg/ml). In the genetic cohort (3b), serum NfL levels were lower in asymptomatic than in symptomatic mutation carriers. There was a significant (age-adjusted) longitudinal increase in serum NfL in PD compared with HC. Serum NfL values were significantly positively associated with longitudinal MDS-UPDRS motor and total scores, as well as age. Interpretation We identified NfL as the first blood-based PD progression biomarker. NfL levels in serum samples are increased in PD compared to HC, increase significantly over time in PD, and correlate with a clinical measure of disease severity. Although the specificity of NfL in PD is low and additional, more specific biomarkers are needed, serum NfL is the first blood-based biomarker candidate that could support disease stratification (PD vs. OND), track clinical progression, and might be used to assess responsiveness to neuroprotective treatments.

BACKGROUND: Time to mechanical thrombectomy (MT) is a critical predictor of functional outcomes in large vessel occlusion stroke. This study compares 2 large vessel occlusion stroke treatment approaches: the one-stop management approach (OSM), in which patients are directly transferred to the angiosuite for flat detector computed tomography and MT, versus the conventional approach, which includes multidetector CT before MT. METHODS: Between March 2014 and December 2019, 205 patients with acute ischemic stroke with a National Institutes of Health Stroke Scale (NIHSS) score of ≥7 and symptom onset ≤4.5 hours underwent large vessel occlusion stroke-treatment using the OSM approach at the University Medical Center Göttingen, Germany. After confirmation of LVO, eligible patients received intravenous thrombolysis followed by MT. Ordinal regression corrected for all confounders. Primary end points included door-to-groin and door-to-reperfusion times, NIHSS at discharge, NIHSS improvement, and modified Rankin Scale at 90 days. Propensity score matching accounted for age, sex, NIHSS, thrombolysis, Thrombolysis in Cerebral Ischemia score, and post-MT intracranial hemorrhage. Treatment times were noncensored. RESULTS: Compared with 2470 patients from the German Stroke Registry treated conventionally (non-OSM group), OSM patients had significantly shorter door-to-groin (33.33±±17.91 versus 95.73±±158.33 minutes; P <0.001) and door-to-reperfusion (78.06±±30.33 versus 147.47±±165.32 minutes; P <0.001) times. While baseline NIHSS was similar, OSM patients showed greater NIHSS improvement and better modified Rankin Scale at 90 days (OR, 2.26 [95% CI, 1.16–4.42]; P <0.05). CONCLUSIONS: In this observational trial, direct angiosuite transfer for large vessel occlusion stroke treatment reduces periprocedural times and is associated with improved functional outcomes compared with a conventional approach using multidetector CT before MT. REGISTRATION: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT03356392.