In Vivo Diagnosis of Synucleinopathies: A Comparative Study of Skin Biopsy and RT-QuIC.
| Title: | In Vivo Diagnosis of Synucleinopathies: A Comparative Study of Skin Biopsy and RT-QuIC. |
|---|---|
| Authors: | Donadio V; From the IRCCS Istituto delle Scienze Neurologiche di Bologna (V.D., A.I., G.R., E.F., V.V., S.C., M.M., C.S., M.S.M., P.A., R.L.), Italy; and Departments of Pathology and Neurology (Z.W., W.Z.), Case Western Reserve University School of Medicine, Cleveland, OH. vincenzo.donadio@unibo.it.; Wang Z; From the IRCCS Istituto delle Scienze Neurologiche di Bologna (V.D., A.I., G.R., E.F., V.V., S.C., M.M., C.S., M.S.M., P.A., R.L.), Italy; and Departments of Pathology and Neurology (Z.W., W.Z.), Case Western Reserve University School of Medicine, Cleveland, OH.; Incensi A; From the IRCCS Istituto delle Scienze Neurologiche di Bologna (V.D., A.I., G.R., E.F., V.V., S.C., M.M., C.S., M.S.M., P.A., R.L.), Italy; and Departments of Pathology and Neurology (Z.W., W.Z.), Case Western Reserve University School of Medicine, Cleveland, OH.; Rizzo G; From the IRCCS Istituto delle Scienze Neurologiche di Bologna (V.D., A.I., G.R., E.F., V.V., S.C., M.M., C.S., M.S.M., P.A., R.L.), Italy; and Departments of Pathology and Neurology (Z.W., W.Z.), Case Western Reserve University School of Medicine, Cleveland, OH.; Fileccia E; From the IRCCS Istituto delle Scienze Neurologiche di Bologna (V.D., A.I., G.R., E.F., V.V., S.C., M.M., C.S., M.S.M., P.A., R.L.), Italy; and Departments of Pathology and Neurology (Z.W., W.Z.), Case Western Reserve University School of Medicine, Cleveland, OH.; Vacchiano V; From the IRCCS Istituto delle Scienze Neurologiche di Bologna (V.D., A.I., G.R., E.F., V.V., S.C., M.M., C.S., M.S.M., P.A., R.L.), Italy; and Departments of Pathology and Neurology (Z.W., W.Z.), Case Western Reserve University School of Medicine, Cleveland, OH.; Capellari S; From the IRCCS Istituto delle Scienze Neurologiche di Bologna (V.D., A.I., G.R., E.F., V.V., S.C., M.M., C.S., M.S.M., P.A., R.L.), Italy; and Departments of Pathology and Neurology (Z.W., W.Z.), Case Western Reserve University School of Medicine, Cleveland, OH.; Magnani M; From the IRCCS Istituto delle Scienze Neurologiche di Bologna (V.D., A.I., G.R., E.F., V.V., S.C., M.M., C.S., M.S.M., P.A., R.L.), Italy; and Departments of Pathology and Neurology (Z.W., W.Z.), Case Western Reserve University School of Medicine, Cleveland, OH.; Scaglione C; From the IRCCS Istituto delle Scienze Neurologiche di Bologna (V.D., A.I., G.R., E.F., V.V., S.C., M.M., C.S., M.S.M., P.A., R.L.), Italy; and Departments of Pathology and Neurology (Z.W., W.Z.), Case Western Reserve University School of Medicine, Cleveland, OH.; Stanzani Maserati M; From the IRCCS Istituto delle Scienze Neurologiche di Bologna (V.D., A.I., G.R., E.F., V.V., S.C., M.M., C.S., M.S.M., P.A., R.L.), Italy; and Departments of Pathology and Neurology (Z.W., W.Z.), Case Western Reserve University School of Medicine, Cleveland, OH.; Avoni P; From the IRCCS Istituto delle Scienze Neurologiche di Bologna (V.D., A.I., G.R., E.F., V.V., S.C., M.M., C.S., M.S.M., P.A., R.L.), Italy; and Departments of Pathology and Neurology (Z.W., W.Z.), Case Western Reserve University School of Medicine, Cleveland, OH.; Liguori R; From the IRCCS Istituto delle Scienze Neurologiche di Bologna (V.D., A.I., G.R., E.F., V.V., S.C., M.M., C.S., M.S.M., P.A., R.L.), Italy; and Departments of Pathology and Neurology (Z.W., W.Z.), Case Western Reserve University School of Medicine, Cleveland, OH.; Zou W; From the IRCCS Istituto delle Scienze Neurologiche di Bologna (V.D., A.I., G.R., E.F., V.V., S.C., M.M., C.S., M.S.M., P.A., R.L.), Italy; and Departments of Pathology and Neurology (Z.W., W.Z.), Case Western Reserve University School of Medicine, Cleveland, OH. |
| Source: | Neurology [Neurology] 2021 May 18; Vol. 96 (20), pp. e2513-e2524. Date of Electronic Publication: 2021 Apr 09. |
| Publication Type: | Comparative Study; Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't |
| Language: | English |
| Journal Info: | Publisher: Lippincott Williams & Wilkins Country of Publication: United States NLM ID: 0401060 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1526-632X (Electronic) Linking ISSN: 00283878 NLM ISO Abbreviation: Neurology Subsets: MEDLINE |
| Imprint Name(s): | Publication: Hagerstown, MD : Lippincott Williams & Wilkins; Original Publication: Minneapolis. |
| MeSH Terms: | Protein Aggregates*; Peripheral Nerves/*metabolism ; Skin/*metabolism ; Synucleinopathies/*diagnosis ; alpha-Synuclein/*metabolism; Alzheimer Disease/metabolism ; Alzheimer Disease/pathology ; Lewy Body Disease/diagnosis ; Lewy Body Disease/metabolism ; Lewy Body Disease/pathology ; Multiple System Atrophy/diagnosis ; Multiple System Atrophy/metabolism ; Multiple System Atrophy/pathology ; Parkinson Disease/diagnosis ; Parkinson Disease/metabolism ; Parkinson Disease/pathology ; Parkinson Disease, Secondary/metabolism ; Parkinson Disease, Secondary/pathology ; Peripheral Nerves/pathology ; Skin/innervation ; Skin/pathology ; Supranuclear Palsy, Progressive/metabolism ; Supranuclear Palsy, Progressive/pathology ; Synucleinopathies/metabolism ; Synucleinopathies/pathology ; TDP-43 Proteinopathies/metabolism ; TDP-43 Proteinopathies/pathology ; Tauopathies/metabolism ; Tauopathies/pathology ; alpha-Synuclein/cerebrospinal fluid ; Aged ; Female ; Fluorescent Antibody Technique ; Humans ; Male ; Middle Aged ; Reproducibility of Results ; Sensitivity and Specificity |
| Abstract: | Objective: To determine whether (1) immunofluorescence is a reproducible technique in detecting misfolded α-synuclein in skin nerves and subsequently whether (2) immunofluorescence and real-time quaking-induced conversion (RT-QuIC) (both in skin and CSF) show a comparable in vivo diagnostic accuracy in distinguishing synucleinopathies from non-synucleinopathies in a large cohort of patients.; Methods: We prospectively recruited 90 patients fulfilling clinical and instrumental diagnostic criteria for all synucleinopathies variants and non-synucleinopathies (mainly including Alzheimer disease, tauopathies, and vascular parkinsonism or dementia). Twenty-four patients with mainly peripheral neuropathies were used as controls. Patients underwent skin biopsy for immunofluorescence and RT-QuIC; CSF was examined in patients who underwent lumbar puncture for diagnostic purposes. Immunofluorescence and RT-QuIC analysis were made blinded to the clinical diagnosis.; Results: Immunofluorescence showed reproducible results between 2 pairs of neighboring skin samples. Both immunofluorescence and RT-QuIC showed high sensitivity and specificity in discriminating synucleinopathies from non-synucleinopathies and controls but immunofluorescence presented higher diagnostic accuracy. Immunofluorescence presented a good level of agreement with RT-QuIC in both skin and CSF in synucleinopathies.; Conclusions: Both immunofluorescence and RT-QuIC showed high diagnostic accuracy, although immunofluorescence displayed the better value as well as optimal reproducibility; they presented a good level of agreement in synucleinopathies, supporting the use of less invasive tests such as skin immunofluorescence or RT-QuIC instead of CSF RT-QuIC as a diagnostic tool for synucleinopathies.; Classification of Evidence: This study provides Class III evidence that immunofluorescence or RT-QuIC accurately distinguish synucleinopathies from non-synucleinopathies.; (Copyright © 2021 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.) |
| Comments: | Comment in: Neurology. 2021 May 18;96(20):925-926. doi: 10.1212/WNL.0000000000011929.. (PMID: 33858996); Erratum in: Neurology. 2022 Jul 5;99(1):40-42. doi: 10.1212/WNL.0000000000200689.. (PMID: 35379763) |
| References: | Neurology. 2017 Jul 4;89(1):88-100. (PMID: 28592453); J Neuropathol Exp Neurol. 2018 Oct 1;77(10):942-949. (PMID: 30137426); Mov Disord. 2015 Oct;30(12):1688-92. (PMID: 26175301); J Neurol Neurosurg Psychiatry. 1988 Jun;51(6):745-52. (PMID: 2841426); Eur J Neurol. 2019 Oct;26(10):1245-1251. (PMID: 30770596); Mov Disord. 2020 Sep;35(9):1649-1657. (PMID: 32557839); Mov Disord. 2019 Oct;34(10):1452-1463. (PMID: 31322768); Acta Neuropathol. 2014 Jul;128(1):99-109. (PMID: 24788821); Acta Neuropathol. 2020 Jul;140(1):49-62. (PMID: 32342188); Acta Neuropathol Commun. 2018 Feb 9;6(1):7. (PMID: 29422107); Clin Auton Res. 2019 Dec;29(6):587-593. (PMID: 31673840); J Neurol Neurosurg Psychiatry. 1994 Apr;57(4):416-8. (PMID: 8163988); Neurology. 1996 Jul;47(1):1-9. (PMID: 8710059); JAMA Neurol. 2020 Sep 28;:. (PMID: 32986090); J Neurol Sci. 2004 Nov 15;226(1-2):81-7. (PMID: 15537526); Neurology. 2008 Aug 26;71(9):670-6. (PMID: 18725592); Neurology. 2013 Feb 19;80(8):725-32. (PMID: 23390175); Mov Disord. 2010 Jan 30;25(2):149-56. (PMID: 20077476); Acta Psychiatr Scand. 1986 Jul;74(1):62-7. (PMID: 3766185); Neurology. 2015 Aug 4;85(5):404-12. (PMID: 26138942); Sci Rep. 2018 Sep 24;8(1):14246. (PMID: 30250046); Clin Neurophysiol. 2008 Mar;119(3):497-503. (PMID: 18164242); Neurology. 2007 Jan 30;68(5):384-6. (PMID: 17082464); Handb Clin Neurol. 2008;89:509-21. (PMID: 18631773); Nat Commun. 2019 Jan 16;10(1):247. (PMID: 30651538); Alzheimers Dement. 2014 Nov;10(6):713-723.e2. (PMID: 24721526); Nat Med. 2011 Feb;17(2):175-8. (PMID: 21278748); Ann Clin Transl Neurol. 2016 Aug 28;3(10):812-818. (PMID: 27752516); Hypertension. 2019 Apr;73(4):910-918. (PMID: 30798661); Neurology. 2017 Jul 25;89(4):318-326. (PMID: 28667178); Sci Transl Med. 2017 Nov 22;9(417):. (PMID: 29167394); Clin Auton Res. 2019 Dec;29(6):577-585. (PMID: 30506233) |
| Grant Information: | U01 NS112010 United States NS NINDS NIH HHS; R21 NS096626 United States NS NINDS NIH HHS; R01 NS109532 United States NS NINDS NIH HHS; R01 AG061388 United States AG NIA NIH HHS; F32 NS009532 United States NS NINDS NIH HHS |
| Substance Nomenclature: | 0 (Protein Aggregates); 0 (SNCA protein, human); 0 (alpha-Synuclein) |
| Entry Date(s): | Date Created: 20210410 Date Completed: 20210531 Latest Revision: 20240923 |
| Update Code: | 20260130 |
| PubMed Central ID: | PMC8205473 |
| DOI: | 10.1212/WNL.0000000000011935 |
| PMID: | 33837116 |
| Database: | MEDLINE |
Comparative Study; Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't