Diagnostic Value of the CSF α-Synuclein Real-Time Quaking-Induced Conversion Assay at the Prodromal MCI Stage of Dementia With Lewy Bodies.

Aged Biomarkers / cerebrospinal fluid Cognitive Dysfunction / cerebrospinal fluid Early Diagnosis Female Fluorescent Antibody Technique Humans Lewy Body Disease / cerebrospinal fluid Male Middle Aged alpha-Synuclein / cerebrospinal fluid

Journal

Neurology
ISSN: 1526-632X
Titre abrégé: Neurology
Pays: United States
ID NLM: 0401060

Informations de publication

Date de publication:
31 08 2021
Historique:
received: 09 11 2020
accepted: 03 06 2021
pubmed: 3 7 2021
medline: 2 10 2021
entrez: 2 7 2021
Statut: ppublish

Résumé

To investigate whether the CSF α-synuclein (α-syn) real-time quaking-induced conversion (RT-QuIC) assay accurately identifies patients with mild cognitive impairment (MCI) due to probable Lewy body (LB) disease. We applied α-syn RT-QuIC to 289 CSF samples obtained from 2 independent cohorts, including 81 patients with probable MCI-LB (age 70.7 ± 6.6 years, 13.6% female, Mini-Mental State Examination [MMSE] score 26.1 ± 2.4), 120 with probable MCI due to Alzheimer disease (AD) (age 68.6 ± 7.4 years, 45.8% female, MMSE score 25.5 ± 2.8), and 30 with unspecified MCI (age 65.4 ± 9.3 years, 30.0% female, MMSE score 27.0 ± 3.0). Fifty-eight individuals with no cognitive decline or evidence of neurodegenerative disease and 121 individuals lacking brain α-syn deposits at the neuropathologic examination were used as controls. RT-QuIC identified patients with MCI-LB against cognitively unimpaired controls with 95% sensitivity, 97% specificity, and 96% accuracy and showed 98% specificity in neuropathologic controls. The accuracy of the test for MCI-LB was consistent between the 2 cohorts (97.3% vs 93.7%). Thirteen percent of patients with MCI-AD also had a positive test; of note, 44% of them developed 1 core or supportive clinical feature of dementia with Lewy bodies (DLB) at follow-up, suggesting an underlying LB copathology. These findings indicate that CSF α-syn RT-QuIC is a robust biomarker for prodromal DLB. Further studies are needed to fully explore the added value of the assay to the current research criteria for MCI-LB. This study provides Class III evidence that CSF α-syn RT-QuIC accurately identifies patients with MCI-LB.

Identifiants

DOI: 10.1212/WNL.0000000000012438 PMID: 34210822 PMC: PMC8408510
pubmed: 34210822
pii: WNL.0000000000012438
doi: 10.1212/WNL.0000000000012438
pmc: PMC8408510
doi:

Substances chimiques

Biomarkers 0
alpha-Synuclein 0

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

e930-e940

Informations de copyright

Written work prepared by employees of the Federal Government as part of their official duties is, under the U.S. Copyright Act, a “work of the United States Government” for which copyright protection under Title 17 of the United States Code is not available. As such, copyright does not extend to the contributions of employees of the Federal Government.

Auteurs

Marcello Rossi (M)

From IRCCS (M.R., S.B., C.Q., A.M., M.S.-M., C.Z., S.C., P.P.), Istituto delle Scienze Neurologiche di Bologna; Department of Experimental, Diagnostic and Specialty Medicine (S.B., P.P.) and Department of Biomedical and Neuromotor Sciences (L.S., S.C.), University of Bologna, Italy; Neurochemistry Laboratory, Department of Clinical Chemistry (C.E.T.), and Department of Neurology (M.v.d.B., W.M.V.d.F., A.W.L.), Alzheimer Center Amsterdam, Amsterdam Neuroscience, Vrije Universiteit Amsterdam, Amsterdam UMC, the Netherlands; and LPVD (B.C.), Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, NIH, Hamilton, MT.
ORCID: 0000-0002-8125-6571

Simone Baiardi (S)

From IRCCS (M.R., S.B., C.Q., A.M., M.S.-M., C.Z., S.C., P.P.), Istituto delle Scienze Neurologiche di Bologna; Department of Experimental, Diagnostic and Specialty Medicine (S.B., P.P.) and Department of Biomedical and Neuromotor Sciences (L.S., S.C.), University of Bologna, Italy; Neurochemistry Laboratory, Department of Clinical Chemistry (C.E.T.), and Department of Neurology (M.v.d.B., W.M.V.d.F., A.W.L.), Alzheimer Center Amsterdam, Amsterdam Neuroscience, Vrije Universiteit Amsterdam, Amsterdam UMC, the Netherlands; and LPVD (B.C.), Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, NIH, Hamilton, MT.
ORCID: 0000-0002-7702-7856

Charlotte E Teunissen (CE)

From IRCCS (M.R., S.B., C.Q., A.M., M.S.-M., C.Z., S.C., P.P.), Istituto delle Scienze Neurologiche di Bologna; Department of Experimental, Diagnostic and Specialty Medicine (S.B., P.P.) and Department of Biomedical and Neuromotor Sciences (L.S., S.C.), University of Bologna, Italy; Neurochemistry Laboratory, Department of Clinical Chemistry (C.E.T.), and Department of Neurology (M.v.d.B., W.M.V.d.F., A.W.L.), Alzheimer Center Amsterdam, Amsterdam Neuroscience, Vrije Universiteit Amsterdam, Amsterdam UMC, the Netherlands; and LPVD (B.C.), Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, NIH, Hamilton, MT.
ORCID: 0000-0002-4061-0837

Corinne Quadalti (C)

From IRCCS (M.R., S.B., C.Q., A.M., M.S.-M., C.Z., S.C., P.P.), Istituto delle Scienze Neurologiche di Bologna; Department of Experimental, Diagnostic and Specialty Medicine (S.B., P.P.) and Department of Biomedical and Neuromotor Sciences (L.S., S.C.), University of Bologna, Italy; Neurochemistry Laboratory, Department of Clinical Chemistry (C.E.T.), and Department of Neurology (M.v.d.B., W.M.V.d.F., A.W.L.), Alzheimer Center Amsterdam, Amsterdam Neuroscience, Vrije Universiteit Amsterdam, Amsterdam UMC, the Netherlands; and LPVD (B.C.), Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, NIH, Hamilton, MT.

Marleen van de Beek (M)

From IRCCS (M.R., S.B., C.Q., A.M., M.S.-M., C.Z., S.C., P.P.), Istituto delle Scienze Neurologiche di Bologna; Department of Experimental, Diagnostic and Specialty Medicine (S.B., P.P.) and Department of Biomedical and Neuromotor Sciences (L.S., S.C.), University of Bologna, Italy; Neurochemistry Laboratory, Department of Clinical Chemistry (C.E.T.), and Department of Neurology (M.v.d.B., W.M.V.d.F., A.W.L.), Alzheimer Center Amsterdam, Amsterdam Neuroscience, Vrije Universiteit Amsterdam, Amsterdam UMC, the Netherlands; and LPVD (B.C.), Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, NIH, Hamilton, MT.

Angela Mammana (A)

From IRCCS (M.R., S.B., C.Q., A.M., M.S.-M., C.Z., S.C., P.P.), Istituto delle Scienze Neurologiche di Bologna; Department of Experimental, Diagnostic and Specialty Medicine (S.B., P.P.) and Department of Biomedical and Neuromotor Sciences (L.S., S.C.), University of Bologna, Italy; Neurochemistry Laboratory, Department of Clinical Chemistry (C.E.T.), and Department of Neurology (M.v.d.B., W.M.V.d.F., A.W.L.), Alzheimer Center Amsterdam, Amsterdam Neuroscience, Vrije Universiteit Amsterdam, Amsterdam UMC, the Netherlands; and LPVD (B.C.), Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, NIH, Hamilton, MT.

Michelangelo Stanzani-Maserati (M)

From IRCCS (M.R., S.B., C.Q., A.M., M.S.-M., C.Z., S.C., P.P.), Istituto delle Scienze Neurologiche di Bologna; Department of Experimental, Diagnostic and Specialty Medicine (S.B., P.P.) and Department of Biomedical and Neuromotor Sciences (L.S., S.C.), University of Bologna, Italy; Neurochemistry Laboratory, Department of Clinical Chemistry (C.E.T.), and Department of Neurology (M.v.d.B., W.M.V.d.F., A.W.L.), Alzheimer Center Amsterdam, Amsterdam Neuroscience, Vrije Universiteit Amsterdam, Amsterdam UMC, the Netherlands; and LPVD (B.C.), Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, NIH, Hamilton, MT.

Wiesje M Van der Flier (WM)

From IRCCS (M.R., S.B., C.Q., A.M., M.S.-M., C.Z., S.C., P.P.), Istituto delle Scienze Neurologiche di Bologna; Department of Experimental, Diagnostic and Specialty Medicine (S.B., P.P.) and Department of Biomedical and Neuromotor Sciences (L.S., S.C.), University of Bologna, Italy; Neurochemistry Laboratory, Department of Clinical Chemistry (C.E.T.), and Department of Neurology (M.v.d.B., W.M.V.d.F., A.W.L.), Alzheimer Center Amsterdam, Amsterdam Neuroscience, Vrije Universiteit Amsterdam, Amsterdam UMC, the Netherlands; and LPVD (B.C.), Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, NIH, Hamilton, MT.
ORCID: 0000-0001-8766-6224

Luisa Sambati (L)

From IRCCS (M.R., S.B., C.Q., A.M., M.S.-M., C.Z., S.C., P.P.), Istituto delle Scienze Neurologiche di Bologna; Department of Experimental, Diagnostic and Specialty Medicine (S.B., P.P.) and Department of Biomedical and Neuromotor Sciences (L.S., S.C.), University of Bologna, Italy; Neurochemistry Laboratory, Department of Clinical Chemistry (C.E.T.), and Department of Neurology (M.v.d.B., W.M.V.d.F., A.W.L.), Alzheimer Center Amsterdam, Amsterdam Neuroscience, Vrije Universiteit Amsterdam, Amsterdam UMC, the Netherlands; and LPVD (B.C.), Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, NIH, Hamilton, MT.

Corrado Zenesini (C)

From IRCCS (M.R., S.B., C.Q., A.M., M.S.-M., C.Z., S.C., P.P.), Istituto delle Scienze Neurologiche di Bologna; Department of Experimental, Diagnostic and Specialty Medicine (S.B., P.P.) and Department of Biomedical and Neuromotor Sciences (L.S., S.C.), University of Bologna, Italy; Neurochemistry Laboratory, Department of Clinical Chemistry (C.E.T.), and Department of Neurology (M.v.d.B., W.M.V.d.F., A.W.L.), Alzheimer Center Amsterdam, Amsterdam Neuroscience, Vrije Universiteit Amsterdam, Amsterdam UMC, the Netherlands; and LPVD (B.C.), Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, NIH, Hamilton, MT.

Byron Caughey (B)

From IRCCS (M.R., S.B., C.Q., A.M., M.S.-M., C.Z., S.C., P.P.), Istituto delle Scienze Neurologiche di Bologna; Department of Experimental, Diagnostic and Specialty Medicine (S.B., P.P.) and Department of Biomedical and Neuromotor Sciences (L.S., S.C.), University of Bologna, Italy; Neurochemistry Laboratory, Department of Clinical Chemistry (C.E.T.), and Department of Neurology (M.v.d.B., W.M.V.d.F., A.W.L.), Alzheimer Center Amsterdam, Amsterdam Neuroscience, Vrije Universiteit Amsterdam, Amsterdam UMC, the Netherlands; and LPVD (B.C.), Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, NIH, Hamilton, MT.

Sabina Capellari (S)

From IRCCS (M.R., S.B., C.Q., A.M., M.S.-M., C.Z., S.C., P.P.), Istituto delle Scienze Neurologiche di Bologna; Department of Experimental, Diagnostic and Specialty Medicine (S.B., P.P.) and Department of Biomedical and Neuromotor Sciences (L.S., S.C.), University of Bologna, Italy; Neurochemistry Laboratory, Department of Clinical Chemistry (C.E.T.), and Department of Neurology (M.v.d.B., W.M.V.d.F., A.W.L.), Alzheimer Center Amsterdam, Amsterdam Neuroscience, Vrije Universiteit Amsterdam, Amsterdam UMC, the Netherlands; and LPVD (B.C.), Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, NIH, Hamilton, MT.
ORCID: 0000-0003-1631-1439

Afina W Lemstra (AW)

From IRCCS (M.R., S.B., C.Q., A.M., M.S.-M., C.Z., S.C., P.P.), Istituto delle Scienze Neurologiche di Bologna; Department of Experimental, Diagnostic and Specialty Medicine (S.B., P.P.) and Department of Biomedical and Neuromotor Sciences (L.S., S.C.), University of Bologna, Italy; Neurochemistry Laboratory, Department of Clinical Chemistry (C.E.T.), and Department of Neurology (M.v.d.B., W.M.V.d.F., A.W.L.), Alzheimer Center Amsterdam, Amsterdam Neuroscience, Vrije Universiteit Amsterdam, Amsterdam UMC, the Netherlands; and LPVD (B.C.), Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, NIH, Hamilton, MT.

Piero Parchi (P)

From IRCCS (M.R., S.B., C.Q., A.M., M.S.-M., C.Z., S.C., P.P.), Istituto delle Scienze Neurologiche di Bologna; Department of Experimental, Diagnostic and Specialty Medicine (S.B., P.P.) and Department of Biomedical and Neuromotor Sciences (L.S., S.C.), University of Bologna, Italy; Neurochemistry Laboratory, Department of Clinical Chemistry (C.E.T.), and Department of Neurology (M.v.d.B., W.M.V.d.F., A.W.L.), Alzheimer Center Amsterdam, Amsterdam Neuroscience, Vrije Universiteit Amsterdam, Amsterdam UMC, the Netherlands; and LPVD (B.C.), Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, NIH, Hamilton, MT. piero.parchi@unibo.it.
ORCID: 0000-0002-9444-9524

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Classifications MeSH

questionsmedicales.fr › Personnes › Tranches d'âge › Adulte › Sujet âgé › Diagnostic Value of the CSF α-Synuclein...
questionsmedicales.fr › Facteurs biologiques › Marqueurs biologiques › Diagnostic Value of the CSF α-Synuclein...
questionsmedicales.fr › Troubles mentaux › Troubles neurocognitifs › Troubles de la cognition › Dysfonctionnement cognitif › Diagnostic Value of the CSF α-Synuclein...
questionsmedicales.fr › Diagnostic › Diagnostic précoce › Diagnostic Value of the CSF α-Synuclein...
questionsmedicales.fr › Techniques d'investigation › Techniques immunologiques › Technique d'immunofluorescence › Diagnostic Value of the CSF α-Synuclein...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Primates › Haplorhini › Catarrhini › Hominidae › Humains › Diagnostic Value of the CSF α-Synuclein...
questionsmedicales.fr › Troubles mentaux › Troubles neurocognitifs › Démence › Maladie à corps de Lewy › Diagnostic Value of the CSF α-Synuclein...
questionsmedicales.fr › Personnes › Tranches d'âge › Adulte › Adulte d'âge moyen › Diagnostic Value of the CSF α-Synuclein...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Protéines associées à la maladie de Parkinson › alpha-Synucléine › Diagnostic Value of the CSF α-Synuclein...