Volume : 12, Issue : 01, January – 2025
Title:
INFLAMMATION BIOMARKERS FOR PARKINSON’S DISEASE
Authors :
Dr. Asad Mumtaz, Dr. Adnan Mahmood, Dr. Sana Umar Afridi
Abstract :
Parkinson Disease (PD) is caused by degeneration of dopaminergic neurons. Clinically it is characterized by bradykinesia, rigidity and resting tremors. Pathologically it is characterized by the alpha synuclein(α-SN) aggregate which is its central hallmark. The aetiology of the PD includes exposure to the environmental toxins, low serum urate, genes and sporadic forms of the disease. Till date PD is a clinical diagnosis and with varying degrees of misdiagnosis rate. However almost 80% dopaminergic neurons disintegrated when motor signs begin to appear. Therefore, there is urgent need for the biomarkers that indicate death of the dopaminergic neurons and provide accuracy in diagnosis. Since cerebrospinal fluid (CSF) and imaging biomarkers are already available with varying and inconsistent results. These biomarkers mainly focused exclusively on neuronal proteins (e.g., α-synuclein, tau, and β-amyloid) as these proteins are hallmarks of the pathogenic process. Genetic biomarkers have also significantly contributed in exploring the physiological and pathological process. Most important them is leucine rich repeat kinase (LRRK2) which has role in both sporadic and familial forms of the disease. Inflammation appears also to be an important player in PD pathogenesis. Immune alterations have been reported in the peripheral immune system, with altered cytokine levels and monocyte and lymphocyte subsets. Degeneration of dopaminergic neurons that releases of reactive oxygen species (ROS), chronic activation of microglia, and mitochondrial dysfunction all seems to contribute towards the neuroinflammation observed in the PD patients. Though interaction of different immune cells in the central nervous system (CNS) with microglia and astrocyte has been documented but the exact pathology is unknown. The crosstalk between immune system of the CNS and peripheral immune system via blood brain barrier (BBB) results in generation of cytokines and chemokines that are useful inflammatory biomarkers. Importantly expression of LRRK2 in different immune cells of innate and adaptive immunity and its upregulation via lipopolysaccharide (LPS) further strengths the role of inflammation in the PD pathogenesis. Besides this, T and B lymphocytes infiltration in the brain have been found that play important role in the microglial pathogenesis but exact pathology is uncertain yet. The handling of modified α-SN oligomers disturbs the whole inflammatory pathway and thus releasing different cytokines that aggravates the inflammation. This review focuses on recent advancement in inflammation biomarkers with potential pharmacological.
Cite This Article:
Please cite this article in press Asad Mumtaz et al., Inflammation Biomarkers For Parkinson’s Disease.,Indo Am. J. P. Sci, 2025; 12 (01).
Number of Downloads : 10
References:
1-CH Williams‐Gray, R Wijeyekoon. Serum immune markers and disease progression in an incident Parkinson’s disease cohort (ICICLE‐PD).Disorders, 2016 – Wiley Online
Library.
2-Jean-Marc Taymans, Eugénie Mutez, Matthieu Drouyer, William Sibran and Marie-Christine Chartier-Harlin. LRRK2 detection in human biofluids: potential use as a Parkinson’s disease biomarker? Biochemical Society Transactions (2017) 45 207–212
3- Philippe Rizek MD, Niraj Kumar MD DM, Mandar S. Jog MD. An update on the diagnosis and treatment of Parkinson disease. CMAJ 2016. DOI:10.1503
4-Barbara Schormair, David Kemlink, Brit Mollenhauer, Ondrej Fiala, Gerrit Machetanz , Jan Roth, Riccardo Berutti, Tim M. Strom, Bernhard Haslinger , Claudia Trenkwalder , Daniela Zahorakova, Pavel Martasek , Evzen Ruzicka, Juliane Winkelmann. Diagnostic exome sequencing in early-onset Parkinson’s disease confirms VPS13C as a rare cause of autosomal-recessive Parkinson’s disease. Clin Genet. 2017 Sep 1. doi: 10.1111/cge.13124
5-J Campolo, R De Maria, L Cozzi, M Parolini. Antioxidant and inflammatory biomarkers for the identification of prodromal Parkinson’s disease- Journal of the , 2016
– Elsevier
6-Trezzi JP1,2, Galozzi S3, Jaeger C1, Barkovits K3, Brockmann K4,5, Maetzler W4,5, Berg D4,5,6, Marcus K3, Betsou F2, Hiller K1,7,8, Mollenhauer B9,10.Distinct metabolomic signature in cerebrospinal fluid in early parkinson’s disease. Mov Disord. 2017 Aug 26.
7)- Liu C, Cholerton B, Shi M, Ginghina C, Cain KC, Auinger P; Parkinson Study Group DATATOP Investigators, Zhang J.CSF tau and tau/Aβ42 predict cognitive decline in Parkinson’s disease.Parkinsonism Relat Disord. 2015 Mar;21(3):271-6. doi: 0.1016/j.parkreldis.2014.12.027.
8-D Lindqvist, S Hall, Y Surova, HM Nielsen. Cerebrospinal fluid inflammatory markers in Parkinson’s disease–associations with depression, fatigue, and cognitive impairment.Brain, behavior, and, 2013 – Elsevier.
9.Lori N. Eidson,George T. Kannarkat,Christopher J. Barnum,Jianjun Chang,Jaegwon Chung,Chelsea Caspell-Garcia,Peggy Taylor,Brit Mollenhauer,Michael G. Schlossmacher,Larry Ereshefsky,Mark Yen,Catherine Kopil,Mark Frasier,Kenneth Marek,Vicki S. Hertzberg and Malú G. Tansey. Candidate inflammatory biomarkers display unique relationships with alpha-synuclein and correlate with measures of disease severity in subjects with Parkinson’s disease. Journal of Neuroinflammation 201714:164.
10- Diane B. Miller and James P. O’Callaghan.Biomarkers of Parkinson’s disease: Present and future. Metabolism. 2015 Mar; 64(3 0 1): S40–S46.
11-Rachael A Lawson,1 Alison J Yarnall,1 Gordon W Duncan,1,2 David P Breen,3 Tien K Khoo,4,5 Caroline H Williams-Gray,3 Roger A Barker,3 David J Burn,1 On behalf of the ICICLE-PD study group. Stability of mild cognitive impairment in newly diagnosed Parkinson’s disease. J Neurol Neurosurg 2017 – jnnp.bmj.com
12- Sharvari Lotankar, Kedar S Prabhavalkar, Lokesh K Bhatt.Biomarkers for Parkinson’s Disease: Recent Advancement. Neurosci. Bull. DOI 10.1007/s12264-017-0183-5
13-Simon Sjödin , Oskar Hansson, Annika Öhrfelt , Gunnar Brinkmalm , Henrik Zetterberg, Ann Brinkmalm, Kaj Blennow . Mass Spectrometric Analysis of Cerebrospinal Fluid Ubiquitin in Alzheimer’s Disease and Parkinsonian Disorders . Proteomics Clin Appl. 2017 Oct 3. doi: 10.1002/prca.2017
14-Mollenhauer B, Caspell-Garcia CJ, Coffey CS, Taylor P, Shaw LM, Trojanowski JQ, Singleton A, Frasier M, Marek K, Galasko D; Parkinson’s Progression Marker Initiative.Longitudinal CSF biomarkers in patients with early Parkinson disease and healthy controls. Neurology 2017 Oct 13 pii: 10.1212/WNL
15- Bowman GL. Biomarkers for early detection of Parkinson disease: A scent of consistency with olfactory dysfunction. Neurology 2017;89:1–3
16-Jesper F. Havelund 1, Niels H. H. Heegaard 2,3, Nils J. K. Færgeman 1 and Jan Bert Gramsbergen. Biomarker Research in Parkinson’s Disease Using Metabolite Profiling. Metabolites 2017, 7, 42; doi:10.3390/metabo7030042
17-Han W, Sapkota S, Camicioli R, Dixon RA, Li L. Profiling novel metabolic biomarkers for Parkinson’s disease using in-depth metabolomic analysis. Mov Disord. 2017 Sep 7. doi: 10.1002/mds.27173.
18-Weidong Le, Jie Dong, Song Li, Amos D. Korczyn. Can Biomarkers Help the Early Diagnosis of Parkinson’s Disease? Neurosci. Bull. DOI 10.1007/s12264-017-0174-6
19- Lucilla Parnetti, Anna Castrioto, Davide Chiasserini, Emanuele Persichetti, Nicola Tambasco, Omar El-Agnaf and Paolo Calabresi. Cerebrospinal fluid biomarkers in Parkinson disease. Neurol. 9, 131–140 (2013);
20- Radu Constantinescu and Stefania Mondello. Cerebrospinal fluid biomarker candidates for Parkinsonian disorders.Fronteirs in neurology Jan 2013
21-Sushil Sharma, Carolyn Seungyoun Moon , Azza Khogali , Ali Haidous, Anthony Chabenne ,Comfort Ojo, Miriana Jelebinkov, Yousef Kurdi , Manuchair Ebadi. Biomarkers in Parkinson’s disease (recent update). Neurochemistry International 63 (2013) 201–229
22-K. Kalinderi, S. Bostantjopoulou,L. Fidani.The genetic background of Parkinson’s disease: current progress and future prospects. Acta Neurol Scand DOI: 10.1111/ane.12563
23-Guangwei Du, Mechelle M. Lewis, Christopher Sica, Lu He, James R. Connor, Lan Kong, Richard B. Mailman, and Xuemei Huang. Distinct Progression Pattern of Susceptibility MRI in the Substantia Nigra of Parkinson’s Patients. Movement Disorder. Vol. 00, No. 00, 2018
24- Marios Politis1 , Gennaro Pagano, Flavia Niccolini. Imaging in Parkinson’s Disease. International Review of Neurobiology 2017 Elsevier Inc. ISSN 0074-7742
25-Usman Saeed, Jordana Compagnone, Richard I. Aviv, Antonio P. Strafella, Sandra E. Black,
Anthony E. Lang and Mario Masellis. Imaging biomarkers in Parkinson’s disease and Parkinsonian syndromes: current and emerging concepts .Translational Neurodegeneration (2017) 6:8
26-Carina C. Ferrari and Rodolfo Tarelli.(2011).Parkinson’s Disease and Systemic Inflammation,436813:9
27-Neeraj Joshi1 | Sarika Singh. Updates on immunity and inflammation in Parkinson disease pathology. J Neuro Res. 2017;1–12.
28-Gardet, A., Benita, Y., Li, C., Sands, B.E., Ballester, I., Stevens, C., Korzenik,J.R., Rioux, J.D., Daly, M.J., Xavier, R.J. and Podolsky, D.K.(2011).LRRK2 isinvolved in the IFN-γ response and host response to pathogens.Journal of Immunology, 185:5577–5585
29-Feng Y, Li L, Sun XH.(2011).Monocytes and Alzheimer’s disease.Neuroscience Bulletin,27(2): 115-122
30- Li Chen, Mingshu Mo, Guangning Li, Luan Cen, Lei Wei, Yousheng Xiao, Xiang Chen, Shaomin Li,Xinling Yang, Shaogang Qu and Pingyi Xu. The biomarkers of immune dysregulation and inflammation response in Parkinson disease. Chen et al. Translational Neurodegeneration (2016) 5:16
30- Lindqvist D1, Hall S, Surova Y, Nielsen HM, Janelidze S, Brundin L, Hansson O. Cerebrospinal fluid inflammatory markers in Parkinson’s disease–associations with depression, fatigue, and cognitive impairment. Brain Behav Immun. 2013 Oct;33:183-9. doi: 10.1016/j.bbi.2013.07.007. Epub 2013 Jul 31.
31-Karlijn J. Doorn , Paul J. Lucassen , Hendrikus W. Boddeke , Marloes Prins , Henk W. Berendse , Benjamin Drukarch , Anne-Marie van Dam. Emerging roles of microglial activation and non-motor symptoms in Parkinson’s disease. Progress in Neurobiology 98 (2012) 222–238.
32-Natália Pessoa Rocha, Aline Silva de Miranda, and Antônio Lúcio Teixeira. Insights into Neuroinflammation in Parkinson’s Disease: From Biomarkers to Anti-Inflammatory Based Therapies. BioMed Research International Volume 2015, Article ID 628192, 12 pages.