Validad diagnóstica de biomarcadores en la enfermedad de Parkinson: una revisión sistemática y metaanálisis

Costa, Maria Fernanda Baeta Neves Alonso da; Reisdorfer, Emilene; Kempfer, Silvana Silveira; Fernandes, Gisele Cristina Manfrini; Porporatti, André Luís; Canto, Graziela De Luca

doi:10.1590/0034-7167-2017-0822

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REVIEW • Rev. Bras. Enferm. 71 (6) • Nov-Dec 2018 • https://doi.org/10.1590/0034-7167-2017-0822 copiar

Validad diagnóstica de biomarcadores en la enfermedad de Parkinson: una revisión sistemática y metaanálisis

Autoría SCIMAGO INSTITUTIONS RANKINGS

RESUMEN

Objetivo:

Identificar los biomarcadores para la enfermedad de Parkinson, el líquido cefalorraquídeo, la sangre, la saliva y la orina.

Método:

Los estudios fueron recolectados en las bases de datos Cochrane, LILACS, PubMed, SCOPUS, WEB OF SCIENCE, OpenGrey, ProQuest y Google Scholar, a partir del 3 de mayo de 2016 y actualizados el 20 de marzo de 2017. Se seleccionaron 22 estudios, evaluados por la Quality Assessment Tool for Diagnostic Accuracy Studies y el Review Manager 5.3.

Resultados:

La evidencia muestra que los anticuerpos séricos pueden ser utilizados como biomarcadores altamente específicos y precisos para el diagnóstico de la enfermedad de Parkinson en su inicio. Los biomarcadores en el líquido cefalorraquídeo están relacionados con el aumento de la severidad motora, la inestabilidad postural, el disturbio de la marcha y la declinación cognitiva.

Conclusión:

Los anticuerpos séricos y cefalorraquídeos pueden utilizarse como biomarcadores de diagnóstico al inicio de la enfermedad.

Descriptores:
Revisión; Enfermedad de Parkinson; Diagnóstico; Biomarcadores; Sangre

Author	Sample (N)	PD (n)	Control (n)	Biomarkers	Accuracy (%)	Sensitivity (%)	Specificity (%)
Aasly et al ⁽²³⁾23 Aasly JO, Johansen KK, Bronstad G, Waro BJ, Majbour NK, Varghese S, et al. Elevated levels of cerebrospinal fluid alpha-synuclein oligomers in healthy asymptomatic LRRK2 mutation carriers. Frontiers Aging Neurosci[Internet]. 2014[cited 2017 May 23];6:248. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4174885/pdf/fnagi-06-00248.pdf https://www.ncbi.nlm.nih.gov/pmc/article... (2014)				α-synuclein; o- α- synuclein; t-α- synuclein; LRRK2	α-synuclein: 74.00 o- α- synuclein: 79.00 t-α- synuclein; 64.00 LRRK2:66.00	α-synuclein: 65.00 o- α- synuclein: 73.00 t-α- synuclein; 53.00 LRRK2:63.00	α-synuclein:83.00 o- α- synuclein: 77.00 t-α- synuclein; 81.00 LRRK2:74.00
Aguiar et al ⁽¹³⁾13 Aguiar PMC, Severino P. Biomarkers in Parkinson Disease: global gene expression analysis in peripheral blood from patients with and without mutations in PARK2 and PARK8. Einstein[Internet]. 2010[cited 2017 May 23];8(3 Pt 1):291-7. Available from: http://apps.einstein.br/revista/arquivos/PDF/1674-Einsteinv8n3_pg291-7_eng.pdf http://apps.einstein.br/revista/arquivos... (2010)	15	10	5	PARK2 ou PARK8
Boll et al ⁽²²⁾22 Boll MC, Alcaraz-Zubeldia M, Montes S, Rios C. Free copper, ferroxidase and SOD1 activities, lipid peroxidation and NO(x) content in the CSF: a different marker profile in four neurodegenerative diseases. Neurochem Res[Internet]. 2008[cited 2017 May 28];33(9):1717-23. Available from: https://link.springer.com/article/10.1007%2Fs11064-008-9610-3 https://link.springer.com/article/10.100... (2008)	102	22	80	Cu/Zn-SOD; Lipid peroxidation assay; NOx; Celuloplasmin ferroxidase
Cao et al ⁽¹⁶⁾16 Cao XY, Lu JM, Zhao ZQ, Li MC, Lu T, An XS, Xue LJ. MicroRNA biomarkers of Parkinson's disease in serum exosome-like microvesicles. Neurosci Lett[Internet]. 2017[cited 2017 May 23];644:94-9. Available from: http://europepmc.org/abstract/med/28223160 http://europepmc.org/abstract/med/282231... (2017)	149	109	40	miR-24, mi R-30a-3p, mi R-30e-3p, miR-195, miR-223*, mi R-324-3p, mi R-331-5p, mi R-338-3p, miR-505, miR-626, miR- 15b, miR-16-2-3p, miR-19a, miR-19b, miR-29a, miR-29c, mi R-30c, miR-148b, miR-181a, miR-185, miR-221, mi R-339-5p, miR-450b-3p, and miR-1294	miR-19b, 0.75, (0.67–0.82); miR-24, 0,90 (0.85–0.94), and miR-195, 0.69 (0.61–0.77), miR-19b, miR-24 and miR-195. 0.94 (0.91–0.98).	miR-195, 82.6 miR-19b, 68.8 miR-24, 81.7 miR-19b, miR-24 and miR-195: 85.3.	miR-195, 55.0%, ; miR-19b, 77.5%; miR-24, 81.7%, miR-19b, miR-24 and miR-195: 90%
Ding et al ⁽⁵⁾5 Ding H, Huang Z, Chen M, Wang C, Chen X, Chen J, et al. Identification of a panel of five serum miRNAs as a biomarker for Parkinson's disease. Parkinsonism Relat Disord[Internet]. 2016[cited 2017 May 23];22:68-73. Available from: http://www.prd-journal.com/article/S1353-8020 (15)30038-9/pdf http://www.prd-journal.com/article/S1353... (2016)	197	106	91	hsa-miR-195 hsa-miR-15b hsa-miR-221 hsa-miR-181a hsa-miR-185	hsa-miR-195: 73.30 hsa-miR-15b: 89.70 hsa-miR-221: 85.40 hsa-miR-181a: 82.20 hsa-miR-185: 82.00	hsa-miR-195: 68.90 hsa-miR-15b: 76.90 hsa-miR-221: 75.80 hsa-miR-181a: 70.30 hsa-miR-185: 70.00	hsa-miR 195:75.80 hsa-miR 15b:86.80 hsa-miR 221:85.80 hsamiR181a:84.00 hsa-miR 185:83.00
Foulds et al ⁽²⁷⁾27 Foulds PG, Mitchell JD, Parker A, Turner R, Green G, Diggle P, et al. Phosphorylated alpha-synuclein can be detected in blood plasma and is potentially a useful biomarker for Parkinson's disease. Faseb J[Internet]. 2011[cited 2017 May 23];25(12):4127-37. Available from: http://www.fasebj.org/content/25/12/4127.long http://www.fasebj.org/content/25/12/4127... (2011)	62	32	30	phospho- α-synuclein; α-synuclein; oligo- α-synuclein; oligo- phospho- α-synuclein	oligo- phospho- α-synuclein: 62	___	___
Foulds et al ⁽²⁾2 Foulds PG, Diggle P, Mitchell JD, Parker A, Hasegawa M, Masuda-Suzukake M, et al. A longitudinal study on alpha-synuclein in blood plasma as a biomarker for Parkinson's disease. Sci Rep[Internet]. 2013[cited 2017 May 28];3:2540. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3756331/pdf/srep02540.pdf https://www.ncbi.nlm.nih.gov/pmc/article... (2013)	280	189	91	phosphorylated α-synuclein;α-synuclein;	phosphorylated α-synuclein: 71.70 α-synuclein:55.80	___	___
Goldknopf et al ⁽²⁸⁾28 Goldknopf IL, Bryson JK, Strelets I, Quintero S, Sheta EA, Mosqueda M, et al. Abnormal serum concentrations of proteins in Parkinson's disease. Biochem Biophys Res Commun[Internet]. 2009[cited 2017 May 28];389(2):321-7. Available from: http://www.sciencedirect.com/science/article/pii/S0006291X09017392?via%3Dihub http://www.sciencedirect.com/science/art... (2009)	226	29 + 62	57 + 78	A. 57 Biomarkers; B. 21 Biomarkers		A. 57 Biomarkers: 96.40 B. 21 Biomarkers: 92.90	A. 57 Biomarkers: 93.30 B. 21 Biomarkers:93.30
Gorostidi et al ⁽²⁵⁾25 Gorostidi A, Bergareche A, Ruiz-Martinez J, Marti-Masso JF, Cruz M, Varghese S, et al. α-synuclein levels in blood plasma from LRRK2 mutation carriers. PLoS One[Internet]. 2012[cited 2017 May 28];7(12):e52312. Available from: http://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0052312&type=printable http://journals.plos.org/plosone/article... (2012)	275	166	109	LRRK2; α-synuclein; iPD		___	___
Grünblatt et al ⁽¹⁷⁾17 Grunblatt E, Zehetmayer S, Jacob CP, Muller T, Jost WH, Riederer P. Pilot study: peripheral biomarkers for diagnosing sporadic Parkinson's disease. J Neural Transm[Internet]. 2010[cited 2017 May 28];117(12):1387-93. Available from: https://link.springer.com/article/10.1007%2Fs00702-010-0509-1 https://link.springer.com/article/10.100... (2010)	139	105	34	PSMA2; LAMB2; ALDH1A1; HIST1H3E	PSMA2:87.20 LAMB2: 82.50 ALDH1A1:75.80 HIST1H3E: 72.00
Gui et al ⁽¹⁴⁾14 Gui Y, Liu H, Zhang L, Lv W, Hu X. Altered microRNA profiles in cerebrospinal fluid exosome in Parkinson disease and Alzheimer disease. Oncotarget[Internet]. 2015[cited 2017 May 28];6(35):37043-53. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4741914/pdf/oncotarget-06-37043.pdf https://www.ncbi.nlm.nih.gov/pmc/article... (2015)	74	47	27	miR-1; miR-153; miR-409-3p; miR-19b-3p; miR-10ª-5p; miR153/mir-409-3p)	miR-1: 92.00 miR-153: 78.00 miR-409-3p: 97.00 miR-19b-3p: 70.50 miR-10a-5p: 90.00	miR-1: 94.00 miR-153: 93.00 miR-409-3p: 90.00 miR-19b-3p: 94.00 miR-10a-5p: 95.00	miR-1: 94.00 miR-153: 93.00 miR-409-3p: 90.00 miR-19b-3p: 94.00 miR-10a-5p: 95.00
Han et al ⁽²⁹⁾29 Han M, Nagele E, DeMarshall C, Acharya N, Nagele R. Diagnosis of Parkinson's disease based on disease-specific autoantibody profiles in human sera. PLoS One[Internet]. 2012[cited 2017 May 23];7(2):e32383. Available from: http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0032383 http://journals.plos.org/plosone/article... (2012)	69	29	40	Autoantibody (10): NM_001544.2 NM_024754.2 BC051695.1 PHR5001 NM_006790.1 NM_032855.1 BC005858.1 NM_003141.2 BC094687.1 BC027617.1		93.10	100
Kang et al ⁽¹²⁾12 Kang JH, Irwin DJ, Chen-Plotkin AS, Siderowf A, Caspell C, Coffey CS, et al. Association of cerebrospinal fluid beta-amyloid 1-42, T-tau, P-tau181, and alpha-synuclein levels with clinical features of drug-naive patients with early Parkinson disease. JAMA Neurol[Internet]. 2013[cited 2015 Jul 23];70(10):1277-87. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4034348/pdf/nihms573438.pdf https://www.ncbi.nlm.nih.gov/pmc/article... (2013)	102	63	39	Aβ1–42; Tau [T-tau]; [P-tau181]; α-synuclein		___	___
Karlsson et al ⁽²⁴⁾24 Karlsson MK, Sharma P, Aasly J, Toft M, Skogar O, Saebo S, et al. Found in transcription: accurate Parkinson's disease classification in peripheral blood. J Parkinsons Dis[Internet]. 2013[cited 2017 May 28];3(1):19-29. Available from: https://content.iospress.com/download/journal-of-parkinsons-disease/jpd120159?id=journal-of-parkinsons-disease%2Fjpd120159 https://content.iospress.com/download/jo... (2013)	154	79	75	α-synuclein (SNCA/PARK1/4); (PRKN/PARK2); L1 (UCHL-1/PARK5); (PINK1/PARK6); DJ-1 (DJ1/PARK7); (LRRK2/PARK8); (VPS35/PARK17); (EIF4G1/PARK18)
Khoo et al ⁽³⁰⁾30 Khoo SK, Petillo D, Kang UJ, Resau JH, Berryhill B, Linder J, et al. Plasma-based circulating MicroRNA biomarkers for Parkinson's disease. J Parkinsons Dis[Internet];2012[cited 2017 May 23];2(4):321-31. Available from: https://content.iospress.com/articles/journal-of-parkinsons-disease/jpd012144 https://content.iospress.com/articles/jo... (2012)	64	32	32	miR-626; miR-505; miR-222; k-TSP1; k- TSP2; k- TSP3; k-TSP4; k-TSP5; k-TSP1–5; k-TSP1–4; k-TSP1–3; k-TSP1,3,4	___	miR-626: 83.00 miR-505: 72.00 miR-222: 78.00 k-TSP1: 100.00 k- TSP2: 32.00 k- TSP3: 96.00 k-TSP4: 0.00 k-TSP5:0.00 k-TSP1–5: 96.00 k-TSP1–4: 96.00 k-TSP1–3: 96.00 k-TSP1,3,4: 96.00	miR-626: 100.00 miR-505: 97.00 miR-222: 73.00 k-TSP1: 56.00 k- TSP2: 00.00 k- TSP3: 9.00 k-TSP4: 100.00 k-TSP5:20.00 k-TSP1–5: 27.00 k-TSP1–4: 55.00 k-TSP1–3: 55.00 k-TSP1,3,4: 64.00
Margis et al ⁽¹⁰⁾10 Margis R, Rieder CR. Identification of blood microRNAs associated to Parkinsonis disease. J Biotechnol[Internet]. 2011[cited 2017 May 28];152(3):96-101. Available from: http://www.sciencedirect.com/science/article/pii/S0168165611000678?via%3Dihub http://www.sciencedirect.com/science/art... (2011)	16	8	8	miR-1; miR-22; miR 29a; miR-16-2; miR-26a2; miR-30a	___	___	___
Molochnikov et al ⁽¹⁸⁾18 Molochnikov L, Rabey JM, Dobronevsky E, Bonucelli U, Ceravolo R, Frosini D, et al. A molecular signature in blood identifies early Parkinson's disease. Mol Neurodegener[Internet]. 2012[cited 2017 May 28];7:26. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3424147/pdf/1750-1326-7-26.pdf https://www.ncbi.nlm.nih.gov/pmc/article... (2012)	156	92	64	SKP1A; HSPA8; PSMC4; ALDH1A1; HIP2
Park et al ⁽²¹⁾21 Park MJ, Cheon SM, Bae HR, Kim SH, Kim JW. Elevated Levels of a-Synuclein Oligomer in the Cerebrospinal Fluid of Drug-Naïve Patients with Parkinson's Disease. J Clin Neurol[Internet]. 2011[cited 2017 May 23];7(4):215-22. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3259496/pdf/jcn-7-215.pdf https://www.ncbi.nlm.nih.gov/pmc/article... (2011)	52	23	29	α- synuclein oligomer;Total α- synuclein	__	__	__
Parnetti et al ⁽¹⁹⁾19 Parnetti L, Farotti L, Eusebi P, Chiasserini D, De Carlo C, Giannandrea D, et al. Differential role of CSF alpha-synuclein species, tau, and A beta 42 in Parkinson's Disease. Frontiers Aging Neurosci[Internet]. 2014[cited 2017 May 28];6. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3978246/pdf/fnagi-06-00053.pdf https://www.ncbi.nlm.nih.gov/pmc/article... (2014)	69	44	25	Aβ142/t-tau ratio; T-α- synuclein; O-α-synuclein; O/t-α-synuclein	Aβ42/t-tau ratio: 64.00 T-α-syn: 68.00 O-α-syn: 72.00 O/t-α-syn ratio: 78.00	Aβ42/t-tau ratio: 82.00 T-α-syn: 59.00 O-α-syn: 89.00 O/t-α-syn ratio: 82.00	Aβ42/t-tau ratio:56.00 T-α-syn: 80.00 O-α-syn: 48.00 O/t-α-syn ratio: 64.00
Tokuda et al ⁽²⁶⁾26 Tokuda T, Qureshi M, Ardah M, Varghese S, Shehab S, Kasai T, et al. Detection of elevated levels of a-synuclein oligomers in CSF from patients with Parkinson disease. Neurol[Internet]. 2010[cited 2017 May 28];75(20):1766-72. Available from:http://onlinelibrary.wiley.com/o/cochrane/clcentral/articles/665/CN-00772665/frame.html. http://onlinelibrary.wiley.com/o/cochran... (2010)	60	32	28	α-synuclein; oligo/total α- synuclein	α-synuclein: 85.90 oligo/total α- synuclein: 94,80	α-synuclein: 75.00 oligo/total α- synuclein: 89.30	α-synuclein: 87.50 oligo/total α- synuclein:90.60
Vivacqua et ⁽²⁰⁾20 Vivacqua G, Latorre A, Suppa A, Nardi M, Pietracupa S, Mancinelli R, et al. Abnormal Salivary Total and Oligomeric Alpha-Synuclein in Parkinson's Disease. Plos One[Internet]. 2016[cited 2017 May 23];11(3). Available from: http://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0151156&type=printable http://journals.plos.org/plosone/article... (2016)	100	60	40	α-synuclein; oligo/total α- synuclein	__	__	__
Wang et al ⁽¹⁵⁾15 Wang X, Yu S, Li F, Feng T. Detection of alpha-synuclein oligomers in red blood cells as a potential biomarker of Parkinson's disease. Neurosci Lett[Internet]. 2015[cited 2017 May 23];599:115-9. Available from: http://www.sciencedirect.com/science/article/pii/S0304394015003870?via%3Dihub http://www.sciencedirect.com/science/art... (2015)	202	100	102	α-synuclein; oligo/total α- synuclein	76.00	79.00	64.70

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[1] CORRESPONDING AUTHOR: Maria Fernanda Baeta Neves Alonso da Costa. E-mail: fernanda.baeta@ufsc.br