Objectives. To identify changes in the biochemical composition of the plasma in a group of patients at risk of developing Parkinson’s disease (PD) at the prodromal stage in comparison with age-matched controls. Materials and methods. Subjects in the risk group were selected on the basis of the having impairments to sleep, olfaction, and peristalsis. The risk group consisted of 12 people and the control group of eight people. Results. The results showed that of seven catecholamines and their metabolites, the only blood change was in the L-dihydroxyphenylalanine (L-DOPA) level, which decreased in the risk group from the level in controls. A decreased L-DOPA concentration is regarded as a marker for selective degeneration of central and peripheral catecholaminergic neurons in PD. In contrast to L-DOPA, the blood concentrations of seven of 12 sphingomyelins increased. Given that changes in sphingomyelin metabolism are linked with apoptosis, autophagy, and synucleinopathies, increases in their concentrations in the risk group are regarded as indicators of systemic degeneration of central and peripheral neurons. Furthermore, the risk group showed a tendency to decreased urate concentrations, which are endogenous neuroprotectors. Conclusions. The results obtained here suggest that changes in blood L-DOPA, sphingomyelin, and urate levels can serve as diagnostic markers for the development of PD at the prodromal stage.
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References
R. B. Postuma, D. Berg, M. Stern, et al., “MDS clinical diagnostic criteria for Parkinson’s disease,” Mov. Disord., 30, No. 12, 1591–1601 (2015), https://doi.org/10.1002/mds.26424.
M. R. Nodel, “The impact of neuropsychiatric impairments on quality of life of patients with Parkinson’s disease,” Nevrol. Zh., 20, No. 1, 20–25 (2015), https://doi.org/10.18821/1560-9545-2015-20-1-20-27.
M. R. Nodel, Yu. V. Ukraintseva, and N. N. Yakhno, “Rapid eye movements sleep behavioral disorder in Parkinson’s disease,” Nevrol. Zh., 20, No. 6, 28–34 (2015), https://doi.org/10.17116/jnevro20171179115-20.
E. A. Katunina, E. P. Il’ina, G. I. Sadekova, and E. I. Gaisenyuk, “Approaches to early diagnosis of Parkinson’s disease,” Zh. Nevrol. Psikhiatr., 119, No. 6, 119–127 (2019), https://doi.org/10.17116/jnevro2019119061119.
E. Bezard and C. E. Gross, “Compensatory mechanisms in experimental and human parkinsonism: towards a dynamic approach,” Prog. Neurobiol., 55, No. 2, 93–116 (1998), https://doi.org/10.1016/s0301-0082(98)00006-9.
J. Blesa, I. Trigo-Damas, M. Dileone, et al., “Compensatory mechanisms in Parkinson’s disease: Circuits adaptations and role in disease modification,” Exp. Neurol., 298, Part B, 148–161 (2017), https://doi.org/10.1016/j.expneurol.2017.10.002.
Y. Agid, “Parkinson’s disease: pathophysiology,” Lancet, 337, No. 8753, 1321–1324 (1991), https://doi.org/10.1016/0140-6736(91)92989-f.
M. Ugrumov, “Development of early diagnosis of Parkinson’s disease: illusion or reality?” CNS Neurosci. Ther., 26, No. 10, 997–1009 (2020), https://doi.org/10.1111/cns.13429.
B. S. Connolly and A. E. Lang, “Pharmacological treatment of Parkinson disease: a review,” JAMA, 311, No. 16, 1670–1683 (2014), https://doi.org/10.1001/jama.2014.3654.
D. S. Goldstein, “Dysautonomia in Parkinson disease,” Compr. Physiol., 4, No. 2, 805–826 (2014), https://doi.org/10.1002/cphy.c130026.
H. Braak, K. Del Tredici, U. Rüb, et al., “Staging of brain pathology related to sporadic Parkinson’s disease,” Neurobiol. Aging, 24, No. 2, 197–211 (2003), https://doi.org/10.1016/s0197-4580(02)00065-9.
P. Mahlknecht, K. Seppi, and W. Poewe, “The concept of prodromal Parkinson’s disease,” J. Parkinsons Dis., 5, No. 4, 681–697 (2015), https://doi.org/10.3233/JPD-150685.
R. B. Postuma and D. Berg, “Advances in markers of prodromal Parkinson disease,” Nat. Rev. Neurol., 12, No. 11, 622–634 (2016), https://doi.org/10.1038/nrneurol.2016.152.
C. Pont-Sunyer, A. Hotter, C. Gaig, et al., “The onset of nonmotor symptoms in Parkinson’s disease (the ONSET PD study),” Mov. Disord., 30, No. 2, 229–237 (2015), https://doi.org/10.1002/mds.26077.
M. O. Izawa, H. Miwa, Y. Kajimoto, and T. Kondo, “Combination of transcranial sonography, olfactory testing, and MIBG myocardial scintigraphy as a diagnostic indicator for Parkinson’s disease,” Eur. J. Neurol., 19, No. 3, 411–416 (2012), https://doi.org/10.1111/j.1468-1331.2011.03533.x.
H. Y. Shin, E. Y. Joo, S. T. Kim, et al., “Comparison study of olfactory function and substantia nigra hyperechogenicity in idiopathic REM sleep behavior disorder, Parkinson’s disease and normal control,” Neurol. Sci., 34, No. 6, 935–940 (2013), https://doi.org/10.1007/s10072-012-1164-0.
M. Eller and D. R. Williams, “Biological fluid biomarkers in neurodegenerative parkinsonism,” Nat. Rev. Neurol., 5, No. 10, 561–570 (2009), https://doi.org/10.1038/nrneurol.2009.135.
W. Le, J. Dong, S. Li, and A.D. Korczyn, “Can biomarkers help the early diagnosis of Parkinson’s disease?” Neurosci. Bull., 33, No. 5, 535–542 (2017), https://doi.org/10.1007/s12264-017-0174-6.
A. Kim, R. Nigmatullina, Z. Zalyalova, et al., “Upgraded methodology for the development of early diagnosis of Parkinson’s Disease based on searching blood markers in patients and experimental models,” Mol. Neurobiol., 56, No. 5, 3437–3450 (2019), https://doi.org/10.1007/s12035-018-1315-2.
K. Stiasny-Kolster, G. Mayer, S. Schäfer, et al., “The REM sleep behavior disorder screening questionnaire – a new diagnostic instrument,” Mov. Disord., 22, No. 16, 2386–2393 (2007), https://doi.org/10.1002/mds.21740.
S. Fahn and R. L. Elton, S. “UPDRS Development Committee. The Unified Parkinson’s Disease Rating Scale,” in: Recent Developments in Parkinson’s Disease, S. Fahn et al. (eds.), Macmillan Healthcare Information; Florham, NJ (1987), 2nd ed., pp. 153–163, 293–304.
M. Visser, J. Marinus, A. M. Stiggelbout, and J. J. Van Hilten, “Assessment of autonomic dysfunction in Parkinson’s disease: the SCOPA-AUT,” Mov. Disord., 19, No. 11, 1306–1312 (2004), https://doi.org/10.1002/mds.20153.
A. S. Zigmond and R. P. Snaith, “The Hospital Anxiety and Depression Scale,” Acta Psychiatr. Scand., 67, No. 6, 361–370 (1983), https://doi.org/10.1111/j.1600-0447.1983.tb09716.x.
S. E. Starkstein, H. S. Mayberg, T. J. Preziosi, et al., “Reliability, validity, and clinical correlates of apathy in Parkinson’s disease,” J. Neuropsychiatry Clin. Neurosci., 4, No. 2, 134–139 (1992), https://doi.org/10.1176/jnp.4.2.134.
R. G. Brown, A. Dittner, L. Findley, and S. C. Wessely, “The Parkinson Fatigue Scale,” Parkinsonism Relat. Disord., 11, No. 1, 49–55 (2005), https://doi.org/10.1016/j.parkreldis.2004.07.007.
Z. S. Nasreddine, N. A. Phillips, V. Bédirian, et al., “The Montreal Cognitive Assessment, MoCA: a brief screening tool for mild cognitive impairment [published correction appears in J. Am. Geriatr. Soc., 67, No. 9, 1991 (2019)].,” J. Am. Geriatr. Soc., 53, No. 4, 695–699 (2005), https://doi.org/10.1111/j.1532-5415.2005.53221.x.
S. Choi-Kwon, S. W. Han, S. U. Kwon, and J. S. Kim, “Poststroke fatigue: characteristics and related factors,” Cerebrovasc. Dis., 19, No. 2, 84–90 (2005), https://doi.org/10.1159/000082784.
D. Berg, R. B. Postuma, C. H. Adler, et al., “MDS research criteria for prodromal Parkinson’s disease,” Mov. Disord., 30, No. 12, 1600–1611 (2015), https://doi.org/10.1002/mds.26431.
E. A. Kozina, A. R. Kim, A. Y. Kurina, and M. V. Ugrumov, “Cooperative synthesis of dopamine by non-dopaminergic neurons as a compensatory mechanism in the striatum of mice with MPTP-induced Parkinsonism,” Neurobiol. Dis., 98, 108–121 (2017), https://doi.org/10.1016/j.nbd.2016.12.005.
E. G. Bligh and W. J. Dyer, “A rapid method of total lipid extraction and purification,” Can. J. Biochem. Physiol., 37, No. 8, 911–917 (1959), https://doi.org/10.1139/o59-099.
C. A. Antoniades and R. A. Barker, “The search for biomarkers in Parkinson’s disease: a critical review,” Expert Rev. Neurother., 8, No. 12, 1841–1852 (2008), https://doi.org/10.1586/14737175.8.12.1841.
Z. Yu, T. Stewart, J. Aasly, et al., “Combining clinical and biofluid markers for early Parkinson’s disease detection,” Ann. Clin. Transl.Neurol., 5, No. 1, 109–114 (2017), https://doi.org/10.1002/acn3.509.
T. Li and W. Le, “Biomarkers for Parkinson’s disease: How good are they?” Neurosci. Bull., 36, No. 2, 183–194 (2020), https://doi.org/10.1007/s12264-019-00433-1.
O. B. Tysnes and A. Storstein, “Epidemiology of Parkinson’s disease,” J. Neural Transm. (Vienna), 124, No. 8, 901–905 (2017), https://doi.org/10.1007/s00702-017-1686-y.
B. L. B. Marino, L. R. de Souza, K. P. A. Sousa, et al., “Parkinson’s disease: A review from pathophysiology to treatment,” Mini Rev. Med. Chem., 20, No. 9, 754–767 (2020), https://doi.org/10.2174/1389557519666191104110908.
A. V. Alessenko and E. Albi, “Exploring sphingolipid implications in neurodegeneration,” Front. Neurol., 11, 437 (2020), https://doi.org/10.3389/fneur.2020.00437.
G. F. Nixon, “Sphingolipids in infl ammation: pathological implications and potential therapeutic targets,” Br. J. Pharmacol., 158, No. 4, 982–993 (2009), https://doi.org/10.1111/j.1476-5381.2009.00281.x.
G. H. Norris and C. N. Blesso, “Dietary and endogenous sphingolipid metabolism in chronic inflammation,” Nutrients, 9, No. 11, 1180 (2017), https://doi.org/10.3390/nu9111180.
M. J. Jembrek, P. R. Hof, and G. Šimić, “Ceramides in Alzheimer’s Disease: key mediators of neuronal apoptosis induced by oxidative stress and Aβ accumulation,” Oxid. Med. Cell. Longev., 2015, 346783 (2015), https://doi.org/10.1155/2015/346783.
Y. Kiraz, A. Adan, M. Kartal Yandim, and Y. Baran, “Major apoptotic mechanisms and genes involved in apoptosis,” Tumour Biol., 37, No. 7, 8471–8486 (2016), https://doi.org/10.1007/s13277-016-5035-9.
C. Y. Mao, J. Yang, H. Wang, et al., “SMPD1 variants in Chinese Han patients with sporadic Parkinson’s disease,” Parkinsonism Relat. Disord., 34, 59–61 (2017), https://doi.org/10.1016/j.parkreldis.2016.10.014.
J. N. Foo, H. Liany, J. X. Bei, et al., “Rare lysosomal enzyme gene SMPD1 variant (p.R591C) associates with Parkinson’s disease,” Neurobiol. Aging, 34, No. 12, 37–42 (2013), https://doi.org/10.1016/j.neurobiolaging.2013.06.010.
W. S. Kim and G. M. Halliday, “Changes in sphingomyelin level affect alpha-synuclein and ABCA5 expression,” J. Parkinsons Dis., 2, No. 1, 41–46 (2012), https://doi.org/10.3233/JPD-2012-11059.
W. A. den Jager, “Sphingomyelin in Lewy inclusion bodies in Parkinson’s disease,” Arch. Neurol., 21, No. 6, 615–619 (1969), https://doi.org/10.1001/archneur.1969.00480180071006.
M. Vila and S. Przedborski, “Targeting programmed cell death in neurodegenerative diseases,” Nat. Rev. Neurosci., 4, No. 5, 365–375 (2003), https://doi.org/10.1038/nrn1100.
N. Simola, M. Morelli, and A. R. Carta, “The 6-hydroxydopamine model of Parkinson’s disease,” Neurotox. Res., 11, No. 3–4, 151–167 (2007), https://doi.org/10.1007/BF03033565.
F. Cicchetti, J. Drouin-Ouellet, an R. E. Gross, “Environmental toxins and Parkinson’s disease: what have we learned from pesticide-induced animal models?” Trends. Pharmacol. Sci., 30, No. 9, 475–483 (2009), https://doi.org/10.1016/j.tips.2009.06.005.
L. C. Guedes, R. B. Chan, M. A. Gomes, et al., “Serum lipid alterations in GBA-associated Parkinson’s disease,” Parkinsonism Relat. Disord., 44, 58–65 (2017), https://doi.org/10.1016/j.parkreldis.2017.08.026.
S. Cipriani, X. Chen, and M. A. Schwarzschild, “Urate: a novel biomarker of Parkinson’s disease risk, diagnosis and prognosis,” Biomark Med., 4, No. 5, 701–712 (2010), https://doi.org/10.2217/bmm.10.94.
M. Wen, B. Zhou, Y. H. Chen, et al., “Serum uric acid levels in patients with Parkinson’s disease: A meta-analysis,” PLoS One, 12, No. 3, e0173731 (2017), https://doi.org/10.1371/journal.pone.0173731.
R. Uribe-San Martín, P. Venegas Francke, F. López Illanes, et al., “Plasma urate in REM sleep behavior disorder,” Mov. Disord., 28, No. 8, 1150–1151 (2013), https://doi.org/10.1002/mds.25441.
D. J. van Wamelen, R. N. Taddei, A. Calvano, et al., “Serum uric acid levels and non-motor symptoms in Parkinson’s disease,” J. Parkinsons Dis., 10, No. 3, 1003–1010 (2020), https://doi.org/10.3233/jpd-201988.
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Translated from Zhurnal Nevrologii i Psikhiatrii imeni S. S. Korsakova, Vol. 120, No. 12, Iss. 1, pp. 7–17, December, 2020.
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Gusev, E.I., Katunina, E.A., Martinov, M.Y. et al. Development of Early Diagnosis of Parkinson’s Disease Using Premotor Symptoms and Blood Changes as Biomarkers. Neurosci Behav Physi 51, 1050–1058 (2021). https://doi.org/10.1007/s11055-021-01164-5
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DOI: https://doi.org/10.1007/s11055-021-01164-5