LECCIÓN

3

MÓDULO

2

Biomarcadores en la enfermedad de Parkinson: Laboratorio

Dr. Íñigo Ruiz Barrio

Servicio de Neurología, Hospital de la Santa Creu i Sant Pau, Barcelona

Referencias bibliográficas

  1. Beach TG, Adler CH. Importance of low diagnostic Accuracy for early Parkinson's disease. Mov Disord. 2018 Oct;33(10):1551-4. [Pubmed]
  2. Sperling RA, Aisen PS, Beckett LA, Bennett DA, Craft S, Fagan AM, et al. Toward defining the preclinical stages of Alzheimer's disease: recommendations from the National Institute on Aging-Alzheimer's Association workgroups on diagnostic guidelines for Alzheimer's disease. Alzheimers Dement. 2011 May;7(3):280-92. [Pubmed]
  3. Mahlknecht P, Seppi K, Poewe W. The Concept of Prodromal Parkinson's Disease. J Parkinsons Dis. 2015;5(4):681-97. [Pubmed]
  4. Tolosa E, Garrido A, Scholz SW, Poewe W. Challenges in the diagnosis of Parkinson's disease. Lancet Neurol. 2021 May;20(5):385-97. [Pubmed]
  5. Heinzel S, Berg D, Gasser T, Chen H, Yao C, Postuma RB; MDS Task Force on the Definition of Parkinson's Disease. Update of the MDS research criteria for prodromal Parkinson's disease. Mov Disord. 2019 Oct;34(10):1464-70. [Pubmed]
  6. Berg D, Postuma RB, Adler CH, Bloem BR, Chan P, Dubois B, et al. MDS research criteria for prodromal Parkinson's disease. Mov Disord. 2015 Oct;30(12):1600-11. [Pubmed]
  7. Gómez-Benito M, Granado N, García-Sanz P, Michel A, Dumoulin M, Moratalla R. Modeling Parkinson's Disease With the Alpha-Synuclein Protein. Front Pharmacol. 2020 Apr 23;11:356. [Pubmed]
  8. Leak RK, Frosch MP, Beach TG, Halliday GM. Alpha-synuclein: prion or prion-like? Acta Neuropathol. 2019 Oct;138(4):509-14. [Pubmed]
  9. Kordower JH, Chu Y, Hauser RA, Freeman TB, Olanow CW. Lewy body-like pathology in long-term embryonic nigral transplants in Parkinson's disease. Nat Med. 2008 May;14(5):504-6. [Pubmed]
  10. Kordower JH, Dodiya HB, Kordower AM, Terpstra B, Paumier K, Madhavan L, et al. Transfer of host-derived α synuclein to grafted dopaminergic neurons in rat. Neurobiol Dis. 2011 Sep;43(3):552-7. [Pubmed]
  11. Li JY, Englund E, Holton JL, Soulet D, Hagell P, Lees AJ, et al. Lewy bodies in grafted neurons in subjects with Parkinson's disease suggest host-to-graft disease propagation. Nat Med. 2008 May;14(5):501-3. [Pubmed]
  12. Li JY, Englund E, Widner H, Rehncrona S, Björklund A, Lindvall O, Brundin P. Characterization of Lewy body pathology in 12- and 16-year-old intrastriatal mesencephalic grafts surviving in a patient with Parkinson's disease. Mov Disord. 2010 Jun 15;25(8):1091-6. [Pubmed]
  13. Peelaerts W, Bousset L, Van der Perren A, Moskalyuk A, Pulizzi R, Giugliano M, et al. α-Synuclein strains cause distinct synucleinopathies after local and systemic administration. Nature. 2015 Jun 18;522(7556):340-4. [Pubmed]
  14. Lohmann S, Bernis ME, Tachu BJ, Ziemski A, Grigoletto J, Tamgüney G. Oral and intravenous transmission of α-synuclein fibrils to mice. Acta Neuropathol. 2019 Oct;138(4):515-33. [Pubmed]
  15. Van Den Berge N, Ferreira N, Gram H, Mikkelsen TW, Alstrup AKO, Casadei N, et al. Evidence for bidirectional and trans-synaptic parasympathetic and sympathetic propagation of alpha-synuclein in rats. Acta Neuropathol. 2019 Oct;138(4):535-50. [Pubmed]
  16. Volpicelli-Daley LA, Luk KC, Patel TP, Tanik SA, Riddle DM, Stieber A, et al. Exogenous α-synuclein fibrils induce Lewy body pathology leading to synaptic dysfunction and neuron death. Neuron. 2011 Oct 6;72(1):57-71. [Pubmed]
  17. Luk KC, Kehm V, Carroll J, Zhang B, O'Brien P, Trojanowski JQ, Lee VM. Pathological α-synuclein transmission initiates Parkinson-like neurodegeneration in nontransgenic mice. Science. 2012 Nov 16;338(6109):949-53. [Pubmed]
  18. Nimmo JT, Kelly L, Verma A, Carare RO, Nicoll JAR, Dodart JC. Amyloid-β and α-Synuclein Immunotherapy: From Experimental Studies to Clinical Trials. Front Neurosci. 2021 Sep 1;15:733857. [Pubmed]
  19. Simonsen AH, Kuiperij B, El-Agnaf OM, Engelborghs S, Herukka SK, Parnetti L, et al. The utility of α-synuclein as biofluid marker in neurodegenerative diseases: a systematic review of the literature. Biomark Med. 2016;10(1):19-34. [Pubmed]
  20. Cariulo C, Martufi P, Verani M, Azzollini L, Bruni G, Weiss A, et al. Phospho-S129 Alpha-Synuclein Is Present in Human Plasma but Not in Cerebrospinal Fluid as Determined by an Ultrasensitive Immunoassay. Front Neurosci. 2019 Aug 22;13:889. [Pubmed]
  21. Alhajj M, Farhana A. Enzyme Linked Immunosorbent Assay. StatPearls. 2022 Feb 2. Disponible en: [Enlace]
  22. Mollenhauer B, Locascio JJ, Schulz-Schaeffer W, Sixel-Döring F, Trenkwalder C, Schlossmacher MG. α-Synuclein and tau concentrations in cerebrospinal fluid of patients presenting with parkinsonism: a cohort study. Lancet Neurol. 2011 Mar;10(3):230-40. Erratum in: Lancet Neurol. 2011 Apr;10(4):297. [Pubmed]
  23. Parnetti L, Chiasserini D, Bellomo G, Giannandrea D, De Carlo C, Qureshi MM, et al. Cerebrospinal fluid Tau/α-synuclein ratio in Parkinson's disease and degenerative dementias. Mov Disord. 2011 Jul;26(8):1428-35. [Pubmed]
  24. El-Agnaf OM, Salem SA, Paleologou KE, Curran MD, Gibson MJ, Court JA, et al. Detection of oligomeric forms of alpha-synuclein protein in human plasma as a potential biomarker for Parkinson's disease. FASEB J. 2006 Mar;20(3):419-25. [Pubmed]
  25. Lin CH, Liu HC, Yang SY, Yang KC, Wu CC, Chiu MJ. Plasma pS129-α-Synuclein Is a Surrogate Biofluid Marker of Motor Severity and Progression in Parkinson's Disease. J Clin Med. 2019 Oct 3;8(10):1601. [Pubmed]
  26. Vivacqua G, Suppa A, Mancinelli R, Belvisi D, Fabbrini A, Costanzo M, et al. Salivary alpha-synuclein in the diagnosis of Parkinson's disease and Progressive Supranuclear Palsy. Parkinsonism Relat Disord. 2019 Jun;63:143-8. [Pubmed]
  27. Sasaki A, Arawaka S, Sato H, Kato T. Sensitive western blotting for detection of endogenous Ser129-phosphorylated α-synuclein in intracellular and extracellular spaces. Sci Rep. 2015 Sep 18;5:14211. [Pubmed]
  28. Cao Z, Wu Y, Liu G, Jiang Y, Wang X, Wang Z, Feng T. α-Synuclein in salivary extracellular vesicles as a potential biomarker of Parkinson's disease. Neurosci Lett. 2019 Mar 23;696:114-20. [Pubmed]
  29. Hong Z, Shi M, Chung KA, Quinn JF, Peskind ER, Galasko D, et al. DJ-1 and alpha-synuclein in human cerebrospinal fluid as biomarkers of Parkinson's disease. Brain. 2010 Mar;133(Pt 3):713-26. [Pubmed]
  30. Vacchi E, Pinton S, Kaelin-Lang A, Melli G. Targeting Alpha Synuclein Aggregates in Cutaneous Peripheral Nerve Fibers by Free-floating Immunofluorescence Assay. J Vis Exp. 2019 Jun 25;(148). [Pubmed]
  31. Kim JY, Illigens BM, McCormick MP, Wang N, Gibbons CH. Alpha-Synuclein in Skin Nerve Fibers as a Biomarker for Alpha-Synucleinopathies. J Clin Neurol. 2019 Apr;15(2):135-42. [Pubmed]
  32. Donadio V, Wang Z, Incensi A, Rizzo G, Fileccia E, Vacchiano V, et al. In Vivo Diagnosis of Synucleinopathies: A Comparative Study of Skin Biopsy and RT-QuIC. Neurology. 2021 May 18;96(20):e2513-e2524. Erratum in: Neurology. 2022 Jul 5;99(1):40-42. [Pubmed]
  33. Beach TG, Corbillé AG, Letournel F, Kordower JH, Kremer T, Munoz DG, et al. Multicenter Assessment of Immunohistochemical Methods for Pathological Alpha-Synuclein in Sigmoid Colon of Autopsied Parkinson's Disease and Control Subjects. J Parkinsons Dis. 2016 Oct 19;6(4):761-70. [Pubmed]
  34. Malek N, Swallow D, Grosset KA, Anichtchik O, Spillantini M, Grosset DG. Alpha-synuclein in peripheral tissues and body fluids as a biomarker for Parkinson's disease - a systematic review. Acta Neurol Scand. 2014 Aug;130(2):59-72. [Pubmed]
  35. Iranzo A, Fairfoul G, Ayudhaya ACN, Serradell M, Gelpi E, Vilaseca I, et al. Detection of α-synuclein in CSF by RT-QuIC in patients with isolated rapid-eye-movement sleep behaviour disorder: a longitudinal observational study. Lancet Neurol. 2021 Mar;20(3):203-12. [Pubmed]
  36. Stefani A, Iranzo A, Holzknecht E, Perra D, Bongianni M, Gaig C, et al.; SINBAR (Sleep Innsbruck Barcelona) group. Alpha-synuclein seeds in olfactory mucosa of patients with isolated REM sleep behaviour disorder. Brain. 2021 May 7;144(4):1118-26. [Pubmed]
  37. Jiang C, Hopfner F, Katsikoudi A, Hein R, Catli C, Evetts S, et al. Serum neuronal exosomes predict and differentiate Parkinson's disease from atypical parkinsonism. J Neurol Neurosurg Psychiatry. 2020 Jul;91(7):720-9. [Pubmed]
  38. Shahnawaz M, Tokuda T, Waragai M, Mendez N, Ishii R, Trenkwalder C, et al. Development of a Biochemical Diagnosis of Parkinson Disease by Detection of α-Synuclein Misfolded Aggregates in Cerebrospinal Fluid. JAMA Neurol. 2017 Feb 1;74(2):163-72. [Pubmed]
  39. Wang Z, Becker K, Donadio V, Siedlak S, Yuan J, Rezaee M, et al. Skin α-Synuclein Aggregation Seeding Activity as a Novel Biomarker for Parkinson Disease. JAMA Neurol. 2020 Sep 28;78(1):1-11. Erratum in: JAMA Neurol. 2021 Jan 1;78(1):120. [Pubmed]
  40. Rossi M, Candelise N, Baiardi S, Capellari S, Giannini G, Orrù CD, et al. Ultrasensitive RT-QuIC assay with high sensitivity and specificity for Lewy body-associated synucleinopathies. Acta Neuropathol. 2020 Jul;140(1):49-62. Erratum in: Acta Neuropathol. 2020 Aug;140(2):245. [Pubmed]
  41. Manne S, Kondru N, Jin H, Serrano GE, Anantharam V, Kanthasamy A, et al. Blinded RT-QuIC Analysis of α-Synuclein Biomarker in Skin Tissue From Parkinson's Disease Patients. Mov Disord. 2020 Dec;35(12):2230-9. [Pubmed]
  42. Luan M, Sun Y, Chen J, Jiang Y, Li F, Wei L, et al. Diagnostic Value of Salivary Real-Time Quaking-Induced Conversion in Parkinson's Disease and Multiple System Atrophy. Mov Disord. 2022 May;37(5):1059-63. [Pubmed]
  43. Manne S, Kondru N, Jin H, Anantharam V, Huang X, Kanthasamy A, Kanthasamy AG. α-Synuclein real-time quaking-induced conversion in the submandibular glands of Parkinson's disease patients. Mov Disord. 2020 Feb;35(2):268-78. [Pubmed]
  44. Bongianni M, Catalán M, Perra D, Fontana E, Janes F, Bertolotti C, et al. Olfactory swab sampling optimization for α-synuclein aggregate detection in patients with Parkinson's disease. Transl Neurodegener. 2022 Jul 28;11(1):37. Erratum in: Transl Neurodegener. 2022 Aug 12;11(1):38. [Pubmed]
  45. Mollenhauer B, Dakna M, Kruse N, Galasko D, Foroud T, Zetterberg H, et al. Validation of Serum Neurofilament Light Chain as a Biomarker of Parkinson's Disease Progression. Mov Disord. 2020 Nov;35(11):1999-2008. [Pubmed]
  46. Doroszkiewicz J, Groblewska M, Mroczko B. Molecular Biomarkers and Their Implications for the Early Diagnosis of Selected Neurodegenerative Diseases. Int J Mol Sci. 2022 Apr 21;23(9):4610. [Pubmed]