Synukleinopatie a jejich laboratorní biomarkery

Česká verzia

Authors: R. Novobilský ^1,2; P. Kušnierová ^1,3; P. Bártová ^1,2; O. Volný ^1,2; M. Sabela ^1,2; M. Bar ^1,2
Authors place of work: Katedra klinických neurověd, LF OU, Ostrava ¹; Neurologická klinika FN Ostrava ²; Ústav laboratorní medicíny, FN Ostrava ³
Published in the journal: Cesk Slov Neurol N 2021; 84(6): 535-539
Category: Review Article
doi: https://doi.org/10.48095/cccsnn2021535

Summary

Neurodegenerative diseases represent a large and heterogeneous group of disorders. Their common feature is the deposition of a certain pathological protein in brain tissue. The location and distribution of abnormally constituted α-synuclein deposits in central and peripheral nervous system define each respective disorder. The location and distribution of a-synuclein deposits define each respective disorder. Synucleinopathies currently include Parkinson‘s disease, Parkinson‘s disease with dementia, Lewy body dementia, multiple system atrophy, pure autonomic failure, and idiopathic REM sleep disorder. The detection of α-synuclein alone in these diseases has the effect in differentiating them from other neurodegenerative diseases; however, its specificity in the differential diagnosis of individual synucleinopathies is relatively low. Therefore, it is necessary to look for other diagnostic biomarkers that would contribute to the early and accurate diagnosis of individual diseases. At the same time, it is not just a matter of looking for new markers, but also of looking for more available biological samples or body fluids in which these biomarkers can be effectively detected. In the introduction of this review there is a brief description of each disorder and subsequently there is a brief overview of mostly diagnostic laboratory biomarkers. We first present the cerebrospinal fluid biomarkers that reflect the direct neuropathological changes, and then several biomarkers found in peripheral tissues.

Keywords:

multiple system atrophy – biomarkers – Parkinson‘s disease – α-synuclein – Lewy bodies – pure autonomic failure

Zdroje

1. Högl B, Stefani A, Videnovic A. Idiopathic REM sleep behaviour disorder and neurodegeneration – an update. Nat Rev Neurol 2018; 14 (1): 40–55. doi: 10.1038/nrneurol.2017.157.

2. Holec SAM, Woerman AL. Evidence of distinct a-synuclein strains underlying disease heterogeneity. Acta Neuropathol 2021; 142 (1): 73–86. doi: 10.1007/s00401-020-02163-5.

3. George JM. The synucleins. Genome Biol 2002; 3 (1): REVIEWS3002. doi: 10.1186/gb-2001-3-1-reviews3002.

4. Spinelli KJ, Taylor JK, Osterberg VR et al. Presynaptic alpha-synuclein aggregation in a mouse model of Parkinson’s disease. J Neurosci 2014; 34 (6): 2037–2050. doi: 10.1523/JNEUROSCI.2581-13.2014.

5. Marques O, Outeiro TF. Alpha-synuclein: from secretion to dysfunction and death. Cell Death Dis 2012; 3 (7): e350. doi: 10.1038/cddis.2012.94.

6. Ottolini D, Calí T, Szabò I et al. Alpha-synuclein at the intracellular and the extracellular side: functional and dysfunctional implications. Biol Chem 2017; 398 (1): 77–100. doi: 10.1515/hsz-2016-0201.

7. Tu PH, Galvin JE, Baba M et al. Glial cytoplasmic inclusions in white matter oligodendrocytes of multiple system atrophy brains contain insoluble a-synuclein. Ann Neurol 1998; 44 (3): 415–422. doi: 10.1002/ana. 410440324.

8. Spillantini MG, Schmidt ML, Lee VMY et al. Alpha-synuclein in Lewy bodies. Nature 1997; 388 (6645): 839–840. doi: 10.1038/42166.

9. Forman MS, Trojanowski JQ, Lee VM. Neurodegenerative diseases: a decade of discoveries paves the way for therapeutic breakthroughs. Nat Med 2004; 10 (10): 1055–1063. doi: 10.1038/nm1113.

10. Lee KW, Chen W, Junn E et al. Enhanced phosphatase activity attenuates a-synucleinopathy in a mouse model. J Neurosci 2011; 31 (19): 6963–6971. doi: 10.1523/JNEUROSCI.6513-10.2011.

11. Goedert M, Masuda-Suzukake M, Falcon B. Like prions: the propagation of aggregated tau and a-synuclein in neurodegeneration. Brain 2017; 140 (2): 266–278. doi: 10.1093/brain/aww230.

12. Alim MA, Hossain MS, Arima K et al. Tubulin seeds alpha-synuclein fibril formation. J Biol Chem 2002; 277 (3): 2112–2117. doi: 10.1074/jbc.M102981200.

13. Zhou RM, Huang YX, Li XL et al. Molecular interaction of a-synuclein with tubulin influences on the polymerization of microtubule in vitro and structure of microtubule in cells. Mol Biol Rep 2010; 37 (7): 3183–3192. doi: 10.1007/s11033-009-9899-2.

14. Garcia-Reitböck P, Anichtchik O, Bellucci A et al. SNARE protein redistribution and synaptic failure in a transgenic mouse model of Parkinson’s disease. Brain 2010; 133 (7): 2032–2044. doi: 10.1093/brain/awq132.

15. Nemani VM, Lu W, Berge V et al. Increased expression of alpha-synuclein reduces neurotransmitter release by inhibiting synaptic vesicle reclustering after endocytosis. Neuron 2010; 65 (1): 66–79. doi: 10.1016/j.neuron.2009.12.023.

16. Mazzulli JR, Xu YH, Sun Y et al. Gaucher disease glucocerebrosidase and a-synuclein form a bidirectional pathogenic loop in synucleinopathies. Cell 2011; 146 (1): 37–52. doi: 10.1016/j.cell.2011.06.001.

17. Choubey V, Safiulina D, Vaarmann A et al. Mutant A53T alpha-synuclein induces neuronal death by increasing mitochondrial autophagy. J Biol Chem 2011; 286 (12): 10814–10824. doi: 10.1074/jbc.M110.132514.

18. Dasari AKR, Kayed R, Wi S et al. Tau interacts with the c-terminal region of a-synuclein, promoting formation of toxic aggregates with distinct molecular conformations. Biochemistry 2019; 58 (25): 2814–2821. doi: 10.1021/acs.biochem.9b00215.

19. Hirsch EC, Vyas S, Hunot S. Neuroinflammation in Parkinson’s disease. Park Relat Disord 2012; 18 (Suppl 1): S210–S212. doi: 10.1016/s1353-8020 (11) 70065-7.

20. Blum-Degena D, Müller T, Kuhn W et al. Interleukin-1beta and interleukin-6 are elevated in the cerebrospinal fluid of Alzheimer’s and de novo Parkinson’s disease patients. Neurosci Lett 1995; 202 (1–2): 17–20. doi: 10.1016/0304-3940 (95) 12192-7.

21. Mogi M, Harada M, Riederer P et al. Tumor necrosis factor-alpha (TNF-alpha) increases both in the brain and in the cerebrospinal fluid from parkinsonian patients. Neurosci Lett 1994; 165 (1–2): 208–210. doi: 10.1016/0304-3940 (94) 90746-3.

22. Moore DJ, West AB, Dawson VL et al. Molecular pathophysiology of Parkinson’s disease. Annu Rev Neurosci 2005; 28: 57–87. doi: 10.1146/annurev.neuro.28.061604.135718.

23. Braak H, Ghebremedhin E, Rüb U et al. Stages in the development of Parkinson’s disease-related pathology. Cell Tissue Res 2004; 318 (1): 121–134. doi: 10.1007/s00441-004-0956-9.

24. Mollenhauer B, Locascio JJ, Schulz-Schaeffer W et al. a-Synuclein and tau concentrations in cerebrospinal fluid of patients presenting with parkinsonism: a cohort study. Lancet Neurol 2011; 10 (3): 230–240. doi: 10.1016/S1474-4422 (11) 70014-X.

25. Hughes AJ, Daniel SE, Ben-Shlomo Y et al. The accuracy of diagnosis of parkinsonian syndromes in a specialist movement disorder service. Brain 2002; 125 (4): 861–870. doi: 10.1093/brain/awf080.

26. Palma JA, Norcliffe-Kaufmann L, Kaufmann H. Diagnosis of multiple system atrophy. Auton Neurosci 2018; 211: 15–25. doi: 10.1016/j.autneu.2017.10.007.

27. Fanciulli A, Stankovic I, Krismer F et al. Multiple system atrophy. Int Rev Neurobiol 2019; 149: 137–192. doi: 10.1016/bs.irn.2019.10.004.

28. Walker L, Stefanis L, Attems J. Clinical and neuropathological differences between Parkinson’s disease, Parkinson’s disease dementia and dementia with Lewy bodies – current issues and future directions. J Neurochem 2019; 150 (5): 467–474. doi: 10.1111/jnc.14698.

29. McKeith IG, Boeve BF, Dickson DW et al. Diagnosis and management of dementia with Lewy bodies. Neurology 2017; 89 (1): 88–100. doi: 10.1212/WNL.0000000000004058.

30. Larsson V, Torisson G, Londos E. Relative survival in patients with dementia with Lewy bodies and Parkinson’s disease dementia. PLoS One 2018; 13 (8): e0202044. doi: 10.1371/journal.pone.0202044.

31. Williams-Gray CH, Mason SL, Evans JR et al. The CamPaIGN study of Parkinson’s disease: 10-year outlook in an incident population-based cohort. J Neurol Neurosurg Psychiatry 2013; 84 (11): 1258–1264. doi: 10.1136/jnnp-2013-305277.

32. Svenningsson P, Westman E, Ballard C et al. Cognitive impairment in patients with Parkinson’s disease: diagnosis, biomarkers, and treatment. Lancet Neurol 2012; 11 (8): 697–707. doi: 10.1016/S1474-4422 (12) 70152-7.

33. Hepp DH, Vergoossen DLE, Huisman E et al. Distribution and load of amyloid-b pathology in Parkinson disease and dementia with Lewy bodies. J Neuropathol Exp Neurol 2016; 75 (10): 936–945. doi: 10.1093/jnen/nlw070.

34. Olichney JM, Galasko D, Salmon DP et al. Cognitive decline is faster in Lewy body variant than in Alzheimer’s disease. Neurology 1998; 51 (2): 351–357. doi: 10.1212/WNL.51.2.351.

35. Kraybill ML, Larson EB, Tsuang DW et al. Cognitive differences in dementia patients with autopsy-verified AD, Lewy body pathology, or both. Neurology 2005; 64 (12): 2069–2073. doi: 10.1212/01.WNL.0000165987.89198.65.

36. Tokuda T, Salem SA, Allsop D et al. Decreased a-synuclein in cerebrospinal fluid of aged individuals and subjects with Parkinson’s disease. Biochem Biophys Res Commun 2006; 349 (1): 162–166. doi: 10.1016/j.bbrc.2006.08.024.

37. Mollenhauer B, Cullen V, Kahn I et al. Direct quantification of CSF a-synuclein by ELISA and first cross-sectional study in patients with neurodegeneration. Exp Neurol 2008; 213 (2): 315–325. doi: 10.1016/j.expneurol.2008.06.004.

38. Hong Z, Shi M, Chung KA et al. DJ-1 and alpha-synuclein in human cerebrospinal fluid as biomarkers of Parkinson’s disease. Brain 2010; 133 (3): 713–726. doi: 10.1093/brain/awq008.

39. Kasuga K, Tokutake T, Ishikawa A et al. Differential levels of alpha-synuclein, beta-amyloid42 and tau in CSF between patients with dementia with Lewy bodies and Alzheimer’s disease. J Neurol Neurosurg Psychiatry 2010; 81 (6): 608–610. doi: 10.1136/jnnp.2009.197483.

40. Lim X, Yeo JM, Green A et al. The diagnostic utility of cerebrospinal fluid alpha-synuclein analysis in dementia with Lewy bodies – a systematic review and meta-analysis. Parkinsonism Relat Disord 2013; 19 (10): 851–858. doi: 10.1016/j.parkreldis.2013.06.008.

41. Brunnström H, Hansson O, Zetterberg H et al. Correlations of CSF tau and amyloid levels with Alzheimer pathology in neuropathologically verified dementia with Lewy bodies. Int J Geriatr Psychiatry 2013; 28 (7): 738–744. doi: 10.1002/gps.3881.

42. Mulugeta E, Londos E, Ballard C et al. CSF amyloid b38 as a novel diagnostic marker for dementia with Lewy bodies. J Neurol Neurosurg Psychiatry 2011; 82 (2): 160–164. doi: 10.1136/jnnp.2009.199398.

43. Gmitterová K, Gawinecka J, Llorens F et al. Cerebrospinal fluid markers analysis in the differential diagnosis of dementia with Lewy bodies and Parkinson’s disease dementia. Eur Arch Psychiatry Clin Neurosci 2020; 270 (4): 461–470. doi: 10.1007/s00406-018-0928-9.

44. Siderowf A, Xie SX, Hurtig H et al. CSF amyloid beta 1–42 predicts cognitive decline in Parkinson disease. Neurology 2010; 75 (12): 1055–1061. doi: 10.1212/ WNL.0b013e3181f39a78.

45. Liguori C, Paoletti FP, Placidi F et al. CSF biomarkers for early diagnosis of synucleinopathies: focus on idiopathic RBD. Curr Neurol Neurosci Rep 2019; 19 (2): 3. doi: 10.1007/s11910-019-0918-y.

46. El-Agnaf OMA, Salem SA, Paleologou KE et al. Detection of oligomeric forms of alpha-synuclein protein in human plasma as a potential biomarker for Parkinson’s disease. FASEB J 2006; 20 (3): 419–425. doi: 10.1096/fj.03-1449com.

47. Sun ZF, Xiang XS, Chen Z et al. Increase of the plasma a-synuclein levels in patients with multiple system atrophy. Mov Disord 2014; 29 (3): 375–379. doi: 10.1002/mds.25688.

48. Rossi M, Candelise N, Baiardi S et al. Ultrasensitive RT-QuIC assay with high sensitivity and specificity for Lewy body-associated synucleinopathies. Acta Neuropathol 2020; 140 (1): 49–62. doi: 10.1007/s00401-020-02160-8.

49. Shahnawaz M, Mukherjee A, Pritzkow S et al. Discriminating a-synuclein strains in Parkinson’s disease and multiple system atrophy. Nature 2020; 578 (7794): 273–277. doi: 10.1038/s41586-020-1984-7.

50. De Luca CMG, Elia AE, Portaleone SM et al. Efficient RT-QuIC seeding activity for a-synuclein in olfactory mucosa samples of patients with Parkinson’s disease and multiple system atrophy. Transl Neurodegener 2019; 8: 24. doi: 10.1186/s40035-019-0164-x.

51. Waragai M, Nakai M, Wei J et al. Plasma levels of DJ-1 as a possible marker for progression of sporadic Parkinson’s disease. Neurosci Lett 2007; 425 (1): 18–22. doi: 10.1016/j.neulet.2007.08.010.

52. Hall S, Janelidze S, Zetterberg H et al. Cerebrospinal fluid levels of neurogranin in Parkinsonian disorders. Mov Disord 2020; 35 (3): 513–518. doi: 10.1002/mds. 27950.

53. Jellinger KA. Neuropathology of sporadic Parkinson’s disease: evaluation and changes of concepts. Mov Disord 2012; 27 (1): 8–30. doi: 10.1002/mds.23795.

54. Janelidze S, Hertze J, Zetterberg H et al. Cerebrospinal fluid neurogranin and YKL-40 as biomarkers of Alzheimer’s disease. Ann Clin Transl Neurol 2015; 3 (1): 12–20. doi: 10.1002/acn3.266.

55. Wang SY, Chen W, Xu W et al. Neurofilament light chain in cerebrospinal fluid and blood as a biomarker for neurodegenerative diseases: a systematic review and meta-analysis. J Alzheimers Dis 2019; 72 (4): 1353–1361. doi: 10.3233/JAD-190615.

56. Singer W, Schmeichel AM, Shahnawaz M et al. Alpha-synuclein oligomers and neurofilament light chain predict phenoconversion of pure autonomic failure. Ann Neurol 2021; 89 (6): 1212–1220. doi: 10.1002/ana.26 089.

57. Hansson O, Janelidze S, Hall S et al. Blood-based NfL: a biomarker for differential diagnosis of parkinsonian disorder. Neurology 2017; 88 (10): 930–937. doi: 10.1212/WNL. 0000000000003680.

58. Qiang JK, Wong YC, Siderowf A et al. Plasma apolipoprotein A1 as a biomarker for Parkinson disease. Ann Neurol 2013; 74 (1): 119–127. doi: 10.1002/ana.23872.

59. Kataoka H, Sugie K. Serum adiponectin levels between patients with Parkinson’s disease and those with PSP. Neurol Sci 2020; 41 (5): 1125–1131. doi: 10.1007/s10072-019-04216-4.

60. Brajkovic L, Kostic V, Sobic-Saranovic D et al. The utility of FDG-PET in the differential diagnosis of Parkinsonism. Neurol Res 2017; 39 (8): 675–684. doi: 10.1080/01616412.2017.1312211.