Relationship between Plasma Level of Beta-amyloid, Alpha-synuclein, and Tau Protein with Cognitive Impairment in Parkinson Disease
DOI:
https://doi.org/10.3889/oamjms.2022.7940Keywords:
Alpha-synuclein, Beta-amyloid, Cognitive impairment, Parkinson’s disease, Tau proteinAbstract
Background: Most people with Parkinson’s disease will develop dementia along with their illness development. There are several overlapping brain pathological features in patients with Parkinson's and Alzheimer's disease. These features are related with beta-amyloid findings, alpha-synuclein and tau protein.
Aim: This study was designed to determine the relationship between beta-amyloid, alpha-synuclein and tau protein plasma level with cognitive impairment in Parkinson’s disease.
Materials and Methods: This was an observational with case-control design study. Total of 62 patients with Parkinson’s disease and 20 healthy controls were included in this study. Parkinson’s disease group was divided into 2 subgroups, patient with and without cognitive impairment based on Montreal Cognitive Assessment Indonesian version (MoCA-Ina) score. The plasma levels of beta-amyloid, alpha-synuclein, and tau protein were measured by using enzyme-linked immunoassay technique. Student’s t-test was used to analyze normally distributed data of plasma level differences between groups (Parkinson’s disease group; control group) and subgroups (Parkinson disease with and without cognitive impairment). If the data was not normally distributed, we used Mann-Whitney test. The level of significancy was <0.05 (p value <0.05).
Results: The result demonstrated significant differences in beta-amyloid, alpha-synuclein, and tau protein plasma level between Parkinson’s disease and control group (p<0.05). We also found significant differences of beta-amyloid plasma level between Parkinson’s with and without cognitive impairment subgroups (p<0.05), but none in other parameters (p>0.05).
Conclusion: Low plasma levels of beta-amyloid 42 (Aβ42) are associated with cognitive impairment in patients with Parkinson’s disease.
Downloads
Metrics
Plum Analytics Artifact Widget Block
References
Aarsland D, Andersen K, Larsen JP, Lolk A, Nielsen H, Kragh-Sørensen P. Risk of dementia in Parkinson’s disease: A community-based, prospective study. Neurology. 2001;56(6):730-6. https://doi.org/10.1212/wnl.56.6.730 PMid:11274306
Emre M, Aarsland D, Brown R, Burn DJ, Duyckaerts C, Mizuno Y, et al. Clinical diagnostic criteria for dementia associated with Parkinson’s disease. Mov Disord. 2007;22(12):1689-707. https://doi.org/10.1002/mds.21507 PMid:17542011
Levy G, Schupf N, Tang MX, Cote LJ, Louis ED, Mejia H, et al. Combined effect of age and severity on the risk of dementia in Parkinson’s disease. Ann Neurol. 2002;51(6):722-9. https://doi.org/10.1002/ana.10219 PMid:12112078
Aarsland D, Beyer MK, Kurz MW. Dementia in Parkinson’s disease. Curr Opin Neurol. 2008;21(6):676-82. https://doi.org/10.1097/WCO.0b013e3283168df0 PMid:18989112
Hely MA, Reid WG, Adena MA, Halliday GM, Morris JG. The Sydney multicenter study of Parkinson’s disease: the inevitability of dementia at 20 years. Mov Disord. 2008;23(6):837-44. https:// doi.org/10.1002/mds.21956 PMid:18307261
Halliday G, Hely M, Reid W, Morris J. The progression of pathology in longitudinally followedpatients with Parkinson’s disease. Acta Neuropathol. 2008;115(4):409-15. https://doi.org/10.1007/s00401-008-0344-8 PMid:18231798
Hamilton RL. Lewy bodies in Alzheimer’s disease: A neuropathological review of 145 cases using alpha-synuclein immunohistochemistry. Brain Pathol. 2000;10(3):378-84. https://doi.org/10.1111/j.1750-3639.2000.tb00269.x PMid:10885656
Mikolaenko I, Pletnikova O, Kawas CH, O’Brien R, Resnick SM, Crain B, et al. Alpha-synuclein lesions in normal aging, Parkinson disease, and Alzheimer disease: Evidence from the Baltimore longitudinal study of aging (BLSA). J Neuropathol Exp Neurol. 2005;64:156-62. https://doi.org/10.1093/jnen/64.2.156
Iseki E. Dementia with Lewy bodies: Reclassification of pathological subtypes and boundary with Parkinson’s disease or Alzheimer’s disease. Neuropathology. 2004;24(1):72-8. https://doi.org/10.1111/j.1440-1789.2003.00530.x PMid:15068176
Irwin DJ, White MT, Toledo JB, Xie SX, Robinson JL, Van Deerlin V, et al. Neuropathologic substrates of Parkinson disease dementia. Ann Neurol. 2012;72(4):587-98. https://doi.org/10.1002/ana.23659 PMid:23037886
Jellinger KA, Attems J. Prevalence and impact of vascular and Alzheimer pathologies in Lewy body disease. Acta Neuropathol. 2008;115:427-36. https://doi.org/10.1007/s00401-008-0347-5
Compta Y, Parkkinen L, O’Sullivan SS, Vandrovcova J, Holton JL, Collins C, et al. Lewy and Alzheimer-type pathologies in Parkinson’s disease dementia: Which is more important? Brain. 2011;134(Pt 5):1493-505. https://doi.org/10.1093/brain/awr031 PMid:21596773
Howlett DR, Whitfield D, Johnson M, Attems J, O’Brien JT, Aarsland D, et al. Regional multiple pathology scores are associated with cognitive decline in lewy body dementias. Brain Pathol. 2015;25(4):401-8. https://doi.org/10.1111/bpa.12182 PMid:25103200
Hughes AJ, Daniel SE, Kilford L, Lees AJ. Accuracy of clinical diagnosis of idiopathic Parkinson’s disease: A clinicopathological study of 100 cases. J Neurol Neurosurg Psychiatry. 1992;55(3):181-4. https://doi.org/10.1136/jnnp.55.3.181 PMid:1564476
Chen NC, Chen HL, Li SH, Chang YH, Chen MH, Tsai NW, et al. Plasma levels of α-Synuclein, Aβ-40 and T-tau as biomarkers to predict cognitive impairment in Parkinson’s Disease. Front Aging Neurosci. 2020;12:112. https://doi.org/10.3389/fnagi.2020.00112 PMid:32410983
Goldman JG, Andrews H, Amara A, Naito A, Alcalay RN, Shaw LM, et al. Cerebrospinal fluid, plasma, and saliva in the BioFIND study: Relationships among biomarkers and Parkinson’s disease Features. Mov Disord. 2018;33:282-8. https://doi.org/10.1002/mds.27232
Litvan I, Goldman JG, Tröster AI, Schmand BA, Weintraub D, Petersen RC, et al. Diagnostic criteria for mild cognitive impairment in Parkinson’s disease: Movement disorder society task force guidelines. Mov Disord. 2012;27(3):349-56. https://doi.org/10.1002/mds.24893 PMid:22275317
Spillantini MG, Crowther RA, Jakes R, Hasegawa M, Goedert M. Alpha-Synuclein in filamentous inclusions of Lewy bodies from Parkinson’s disease and dementia with lewy bodies. Proc Natl Acad Sci U S A. 1998;95(11):6469-73. https://doi.org/10.1073/pnas.95.11.6469 PMid:9600990
Vivacqua G, Yin JJ, Casini A, Li X, Li YH, D’Este L, et al. Immunolocalization of alpha-synuclein in the rat spinal cord by two novel monoclonal antibodies. Neuroscience. 2009;158(4):1478-87. https://doi.org/10.1016/j.neuroscience.2008.12.001 PMid:19118601
Alves G, Brønnick K, Aarsland D, Blennow K, Zetterberg H, Ballard C, et al. CSF amyloid-beta and tau proteins, and cognitive performance, in early and untreated Parkinson’s disease: The Norwegian ParkWest study. J Neurol Neurosurg Psychiatry. 2010;81(10):1080-6. https://doi.org/10.1136/jnnp.2009.199950 PMid:20547614
Hu X, Yang Y, Gong D. Changes of cerebrospinal fluid Aβ42, t-tau, and p-tau in Parkinson’s disease patients with cognitive impairment relative to those with normal cognition: A meta-analysis. Neurol Sci. 2017;38(11):1953-61. https://doi.org/10.1007/s10072-017-3088-1 PMid:28808876
Duran R, Barrero FJ, Morales B, Luna JD, Ramirez M, Vives F. Plasma alpha-synuclein in patients with Parkinson’s disease with and without treatment. Mov Disord. 2010;25(4):489-93. https://doi.org/10.1002/mds.22928 PMid:20063406
Lee PH, Lee G, Park HJ, Bang OY, Joo IS, Huh K. The plasma alpha-synuclein levels in patients with Parkinson’s disease and multiple system atrophy. J Neural Transm (Vienna). 2006;113(10):1435-9. https://doi.org/10.1007/s00702-005-0427-9 PMid:16465458
Gorostidi A, Bergareche A, Ruiz-Martínez J, Martí-Massó JF, Cruz M, Varghese S, et al. Αlpha-synuclein levels in blood plasma from LRRK2 mutation carriers. PLoS One. 2012;7(12):e52312. https://doi.org/10.1371/journal.pone.0052312 PMid:23300640
Li QX, Mok SS, Laughton KM, McLean CA, Cappai R, Masters CL, et al. Plasma alpha-synuclein is decreased in subjects with Parkinson’s disease. Exp Neurol. 2007;204(2):583-8. https://doi.org/10.1016/j.expneurol.2006.12.006 PMid:17258710
Bougea A, Stefanis L, Paraskevas GP, Emmanouilidou E, Vekrelis K, Kapaki E. Plasma alpha-synuclein levels in patients with Parkinson’s disease: A systematic review and meta-analysis. Neurol Sci. 2019;40(5):929-938. https://doi.org/10.1007/s10072-019-03738-1 PMid:30715632
Arai T, Ikeda K, Akiyama H, Shikamoto Y, Tsuchiya K, Yagishita S, et al. Distinct isoforms of tau aggregated in neurons and glial cells in brains of patients with Pick’s disease, corticobasal degeneration and progressive supranuclear palsy. Acta Neuropathol. 2001;101(2):167-73. https://doi.org/10.1007/s004010000283 PMid:11271372
Armstrong RA, Cairns NJ. Spatial patterns of the tau pathology in progressive supranuclear palsy. Neurol Sci. 2013;34(3):337-44. https://doi.org/10.1007/s10072-012-1006-0 PMid:22411688
Duda JE, Giasson BI, Mabon ME, Miller DC, Golbe LI, Lee VM, et al. Concurrence of alpha-synuclein and tau brain pathology in the Contursi kindred. Acta Neuropathol. 2002;104(1):7-11. https://doi.org/10.1007/s00401-002-0563-3 PMid:12070658
Kummer MP, Heneka MT. Truncated and modified amyloid-beta species. Alzheimers Res Ther. 2014;6(3):28. https://doi.org/10.1186/alzrt258 PMid:25031638
Haass C, Selkoe DJ. Soluble protein oligomers in neurodegeneration: lessons from the Alzheimer’s amyloid beta-peptide. Nat Rev Mol Cell Biol. 2007;8(2):101-12. https://doi.org/10.1038/nrm2101 PMid:17245412
Hall S, Surova Y, Öhrfelt A, Zetterberg H, Lindqvist D, Hansson O. CSF biomarkers and clinical progression of Parkinson disease. Neurology. 2015;84(1):57-63. https://doi.org/10.1212/WNL.0000000000001098 PMid:25411441
Downloads
Published
How to Cite
Issue
Section
Categories
License
Copyright (c) 2022 Yuliarni Syafrita, Attiya Istarini, Meldayeni Busra, Syarif Indra, Restu Susanti (Author)
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.
This is an open-access article distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 International License (CC BY-NC 4.0)
