Antibody biomarker for de novo Parkinson disease: attempted validation (original) (raw)
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Blood biomarker for Parkinson disease: peptoids
npj Parkinson's Disease, 2016
Parkinson disease (PD) is the second most common neurodegenerative disease. Because dopaminergic neuronal loss begins years before motor symptoms appear, a biomarker for the early identification of the disease is critical for the study of putative neuroprotective therapies. Brain imaging of the nigrostriatal dopamine system has been used as a biomarker for early disease along with cerebrospinal fluid analysis of α-synuclein, but a less costly and relatively non-invasive biomarker would be optimal. We sought to identify an antibody biomarker in the blood of PD patients using a combinatorial peptoid library approach. We examined serum samples from 75 PD patients, 25 de novo PD patients, and 104 normal control subjects in the NINDS Parkinson's Disease Biomarker Program. We identified a peptoid, PD2, which binds significantly higher levels of IgG3 antibody in PD versus control subjects (P o 0.0001) and is 68% accurate in identifying PD. The PD2 peptoid is 84% accurate in identifying de novo PD. Also, IgG3 levels are significantly higher in PD versus control serum (P o 0.001). Finally, PD2 levels are positively correlated with the United Parkinson's Disease Rating Scale score (r = 0.457, P o 0001), a marker of disease severity. The PD2 peptoid may be useful for the early-stage identification of PD, and serve as an indicator of disease severity. Additional studies are needed to validate this PD biomarker.
Pilot study: peripheral biomarkers for diagnosing sporadic Parkinson’s disease
Journal of Neural Transmission, 2010
The need for an early and differential diagnosis of Parkinson's disease (PD) is undoubtedly one of the main quests of the century. An early biomarker would enable therapy to begin sooner and would, hopefully, slow or better prevent progression of the disease. We performed transcript profiling via quantitative RT-PCR in RNA originating from peripheral blood samples. The groups were de novo (n = 11) and medicated PD (n = 94) subjects and healthy controls (n = 34), while for negative control Alzheimer's disease (AD; n = 14) subjects were recruited as an additional neurodegenerative disease. The results were retested on a second recruitment consisting 22 medicated PD subjects versus 33 controls and 12 AD. Twelve transcripts were chosen as candidate genes, according to previous postmortem brain profiling. Multiple analyses resulted in four significant genes: proteasome (prosome, macropain) subunit-alpha type-2 (PSMA2; p = 0.0002, OR = 1.15 95% CI 1.07-1.24), laminin, beta-2 (laminin S) (LAMB2; p = 0.0078, OR = 2.26 95% CI 1.24-4.14), aldehyde dehydrogenase 1 family-member A1 (ALDH1A1; p = 0.016, OR = 1.05 95% CI 1.01-1.1), and histone cluster-1 H3e (HIST1H3E; p = 0.03, OR = 0.975 95% CI 0.953-0.998) differentiating between medicated PD subjects versus controls. Using these four biomarkers for PD diagnosis, we achieved sensitivity and specificity of more than 80%. These biomarkers might be specific for PD diagnosis, since in AD subjects no significant results were observed. In the second validation, three genes (PSMA2, LAMB2 and ALDH1A1) demonstrated high reproducibility. This result supports previous studies of gene expression profiling and may facilitate the development of biomarkers for early diagnosis of PD.
Targeted Discovery and Validation of Plasma Biomarkers of Parkinson’s Disease
J. Proteome Res., 2014
Despite extensive research, an unmet need remains for protein biomarkers of Parkinson's disease (PD) in peripheral body fluids, especially blood, which is easily accessible clinically. The discovery of such biomarkers is challenging, however, due to the enormous complexity and huge dynamic range of human blood proteins, which are derived from nearly all organ systems, with those originating specifically from the central nervous system (CNS) being exceptionally low in abundance. In this investigation of a relatively large cohort (∼300 subjects), selected reaction monitoring (SRM) assays (a targeted approach) were used to probe plasma peptides derived from glycoproteins previously found to be altered in the CNS based on PD diagnosis or severity. Next, the detected peptides were interrogated for their diagnostic sensitivity and specificity as well as the correlation with PD severity, as determined by the Unified Parkinson's Disease Rating Scale (UPDRS). The results revealed that 12 of the 50 candidate glycopeptides were reliably and consistently identified in plasma samples, with three of them displaying significant differences among diagnostic groups. A combination of four peptides (derived from PRNP, HSPG2, MEGF8, and NCAM1) provided an overall area under curve (AUC) of 0.753 (sensitivity: 90.4%; specificity: 50.0%). Additionally, combining two peptides (derived from MEGF8 and ICAM1) yielded significant correlation with PD severity, that is, UPDRS (r = 0.293, p = 0.004). The significance of these results is at least twofold: (1) it is possible to use a targeted approach to identify otherwise very difficult to detect CNS related biomarkers in peripheral blood and (2) the novel biomarkers, if validated in independent cohorts, can be employed to assist with clinical diagnosis of PD as well as monitoring disease progression.
International Journal of Molecular Sciences
Parkinson’s disease (PD) is diagnosed many years after its onset, under a significant degradation of the nigrostriatal dopaminergic system, responsible for the regulation of motor function. This explains the low effectiveness of the treatment of patients. Therefore, one of the highest priorities in neurology is the development of the early (preclinical) diagnosis of PD. The aim of this study was to search for changes in the blood of patients at risk of developing PD, which are considered potential diagnostic biomarkers. Out of 1835 patients, 26 patients were included in the risk group and 20 patients in the control group. The primary criteria for inclusion in a risk group were the impairment of sleep behavior disorder and sense of smell, and the secondary criteria were neurological and mental disorders. In patients at risk and in controls, the composition of plasma and the expression of genes of interest in lymphocytes were assessed by 27 indicators. The main changes that we found i...
Biomarkers in Parkinson s Disease - An Effective Tool for Diagnosis of PD
2021
1 Professor and HOD, Dept. of Pharmacology, Sultan-ul-Uloom College of Pharmacy, Road no.3, Banjara Hills Hyderabad 500034, Telangana, India. 2 M.Pharm, II-Year, Dept. of Pharmacology, Sultan-ul-Uloom College of Pharmacy, Road no.3, Banjara Hills, Hyderabad 500034, Telangana, India. 3 Principal and Professor, Sultan-ul-Uloom College of Pharmacy, Road no.3, Banjara Hills, Hyderabad 500034, Telangana, India.
The N-glycosylation of immunoglobulin G as a novel biomarker of Parkinson's disease
Glycobiology, 2017
The use of the emerging "omics" technologies for large scale population screening is promising in terms of predictive, preventive and personalized medicine. For Parkinson's disease, it is essential that an accurate diagnosis is obtained and disease progression can be monitored. Immunoglobulin G (IgG) has the ability to exert both anti-inflammatory and pro-inflammatory effects, and the N-glycosylation of the fragment crystallizable portion of IgG is involved in this process. This study aimed to determine whether the IgG glycome could be a candidate biomarker for Parkinson's disease. Ninety-four community-based individuals with Parkinson's disease and a sex-, age- and ethnically-matched cohort of 102 individuals with mixed phenotypes, representative of a "normally" aged Caucasian controls, were investigated. Plasma IgG glycans were analyzed by ultra-performance liquid chromatography. Overall, seven glycan peaks and 11 derived traits had statistically si...
Plasma Biomarkers Differentiate Parkinson’s Disease From Atypical Parkinsonism Syndromes
Frontiers in Aging Neuroscience, 2018
Objective: Parkinson's disease (PD) has significant clinical overlaps with atypical parkinsonism syndromes (APS), which have a poorer treatment response and a more aggressive course than PD. We aimed to identify plasma biomarkers to differentiate PD from APS. Methods: Plasma samples (n = 204) were obtained from healthy controls and from patients with PD, dementia with Lewy bodies (DLB), multiple system atrophy, progressive supranuclear palsy (PSP), corticobasal degeneration (CBD), or frontotemporal dementia (FTD) with parkinsonism (FTD-P) or without parkinsonism. We measured plasma levels of α-synuclein, total tau, p-Tau181, and amyloid beta 42 (Aβ42) by immunomagnetic reduction-based immunoassay. Results: Plasma α-synuclein level was significantly increased in patients with PD and APS when compared with controls and FTD without parkinsonism (p < 0.01). Total tau and p-Tau181 were significantly increased in all disease groups compared to controls, especially in patients with FTD (p < 0.01). A multivariate and receiver operating characteristic curve analysis revealed that a cutoff value for Aβ42 multiplied by p-Tau181 for discriminating patients with FTD from patients with PD and APS was 92.66 (pg/ml) 2 , with an area under the curve (AUC) of 0.932. An α-synuclein cutoff of 0.1977 pg/ml could separate FTD-P from FTD without parkinsonism (AUC 0.947). In patients with predominant parkinsonism, an α-synuclein cutoff of 1.388 pg/ml differentiated patients with PD from those with APS (AUC 0.87). Conclusion: Our results suggest that integrated plasma biomarkers improve the differential diagnosis of PD from APS (PSP, CBD, DLB, and FTD-P).
Biomarkers in Parkinson’s disease (recent update)
Neurochemistry International, 2013
Parkinson's disease (PD) is the second most common neurodegenerative disorder mostly affecting the 29 aging population over sixty. Cardinal symptoms including, tremors, muscle rigidity, drooping posture, 30 drooling, walking difficulty, and autonomic symptoms appear when a significant number of nigrostriatal 31 dopaminergic neurons are already destroyed. Hence we need early, sensitive, specific, and economical 32 peripheral and/or central biomarker(s) for the differential diagnosis, prognosis, and treatment of PD. 33 These can be classified as clinical, biochemical, genetic, proteomic, and neuroimaging biomarkers. Novel 34 discoveries of genetic as well as nongenetic biomarkers may be utilized for the personalized treatment of 35 PD during preclinical (premotor) and clinical (motor) stages. Premotor biomarkers including hyper-ech-36 ogenicity of substantia nigra, olfactory and autonomic dysfunction, depression, hyposmia, deafness, REM 37 sleep disorder, and impulsive behavior may be noticed during preclinical stage. Neuroimaging biomark-38 ers (PET, SPECT, MRI), and neuropsychological deficits can facilitate differential diagnosis. Single-cell pro-39 filing of dopaminergic neurons has identified pyridoxal kinase and lysosomal ATPase as biomarker genes 40 for PD prognosis. Promising biomarkers include: fluid biomarkers, neuromelanin antibodies, pathological 41 forms of a-Syn, DJ-1, amyloid b and tau in the CSF, patterns of gene expression, metabolomics, urate, as 42 well as protein profiling in the blood and CSF samples. Reduced brain regional N-acetyl-aspartate is a bio-43 marker for the in vivo assessment of neuronal loss using magnetic resonance spectroscopy and T 2 relax-44 ation time with MRI. To confirm PD diagnosis, the PET biomarkers include [ 18 F]-DOPA for estimating 45 dopaminergic neurotransmission, [ 18 F]dG for mitochondrial bioenergetics, [ 18 F]BMS for mitochondrial 46 complex-1, [ 11 C](R)-PK11195 for microglial activation, SPECT imaging with 123 Iflupane and bCIT for dopa-47 mine transporter, and urinary salsolinol and 8-hydroxy, 2-deoxyguanosine for neuronal loss. This brief 48 review describes the merits and limitations of recently discovered biomarkers and proposes coenzyme 49 Q 10 , mitochondrial ubiquinone-NADH oxidoreductase, melatonin, a-synculein index, Charnoly body, 50 and metallothioneins as novel biomarkers to confirm PD diagnosis for early and effective treatment of PD.
Journal of proteomics, 2013
Diagnosis of Parkinson's disease (PD) is currently assessed by the clinical evaluation of extrapyramidal signs. The identification of specific biomarkers would be advisable, however most studies stop at the discovery phase, with no biomarkers reaching clinical exploitation. To this purpose, we developed an automated literature analysis procedure to retrieve all the background knowledge available in public databases. The bioinformatic platform allowed us to analyze more than 51,000 scientific papers dealing with PD, containing information on 4121 proteins. Out of these, we could track back 35 PD-related proteins as present in at least two published 2-DE maps of human plasma. Then, 9 different proteins (haptoglobin, transthyretin, apolipoprotein A-1, serum amyloid P component, apolipoprotein E, complement factor H, fibrinogen γ, thrombin, complement C3) split into 32 spots were identified as a potential diagnostic pattern. Eventually, we compared the collected literature data to experimental gels from 90 subjects (45 PD patients, 45 non-neurodegenerative control subjects) to experimentally verify their potential as plasma biomarkers of PD. This article is part of a Special Issue entitled: From Genome to Proteome: Open Innovations.► An automated literature analysis procedure retrieved plasma PD biomarkers. ► 9 different proteins were identified as a potential PD diagnostic pattern. ► We verified some candidate biomarkers in 2-DE plasma maps of 90 subjects.