Relevance of Aβ42/40 Ratio for Detection of Alzheimer Disease Pathology in Clinical Routine: The PLMR Scale
Background: Cerebrospinal fluid (CSF) biomarkers (Aβ peptides and tau proteins) improved the diagnosis of Alzheimer’s disease (AD) in research and clinical settings. We previously described the PLM-scale (Paris-Lille-Montpellier study), which combines Aβ42, tau, and phosphorylated ptau(181) biomarke...
| Main Authors: | , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Frontiers Media S.A.
2018-05-01
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| Series: | Frontiers in Aging Neuroscience |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/article/10.3389/fnagi.2018.00138/full |
| _version_ | 1819133146748157952 |
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| author | Sylvain Lehmann Sylvain Lehmann Constance Delaby Constance Delaby Guilaine Boursier Cindy Catteau Nelly Ginestet Laurent Tiers Aleksandra Maceski Sophie Navucet Claire Paquet Julien Dumurgier Eugeen Vanmechelen Hugo Vanderstichele Audrey Gabelle Audrey Gabelle Audrey Gabelle |
| author_facet | Sylvain Lehmann Sylvain Lehmann Constance Delaby Constance Delaby Guilaine Boursier Cindy Catteau Nelly Ginestet Laurent Tiers Aleksandra Maceski Sophie Navucet Claire Paquet Julien Dumurgier Eugeen Vanmechelen Hugo Vanderstichele Audrey Gabelle Audrey Gabelle Audrey Gabelle |
| author_sort | Sylvain Lehmann |
| collection | DOAJ |
| description | Background: Cerebrospinal fluid (CSF) biomarkers (Aβ peptides and tau proteins) improved the diagnosis of Alzheimer’s disease (AD) in research and clinical settings. We previously described the PLM-scale (Paris-Lille-Montpellier study), which combines Aβ42, tau, and phosphorylated ptau(181) biomarkers in an easy to use and clinically relevant way. The purpose of this work is to evaluate an optimized PLMR-scale (PLM ratio scale) that now includes the Aβ42/Aβ40 ratio to detect AD versus non-AD (NAD) participants in clinical routine of memory centers.Methods: Both scales were compared using 904 participants with cognitive impairment recruited from two independent cohorts (Mtp-1 and Mtp-2). The CSF Aβ42/Aβ40 ratio was measured systematically in Mtp-1, and only on biologically discordant cases in Mtp-2. Two different ELISA kit providers were also employed. The distribution of AD and NAD patients and the discrepancies of biomarker profiles were computed. Receiver Operating Characteristic curves were used to represent clinical sensitivity and specificity for AD detection. The classification of patients with the net reclassification index (NRI) was also evaluated.Results: Nine hundred and four participants (342 AD and 562 NAD) were studied; 400 in Mtp-1 and 504 in Mtp-2. For AD patients, the mean CSF Aβ42 and CSF Aβ42/40 ratio was 553 ± 216 pg/mL and 0.069 ± 0.022 pg/mL in Mtp-1 and 702 ± 335 pg/mL and 0.045 ± 0.020 pg/mL in Mtp-2. The distribution of AD and NAD differed between the PLM and the PLMR scales (p < 0.0001). The percentage AD well-classified (class 3) increased with PLMR from 38 to 83% in Mpt-1 and from 33 to 53% in Mpt-2. A sharp reduction of the discordant profiles going from 34 to 16.3% and from 37.5 to 19.8%, for Mtp-1 and Mtp-2 respectively, was also observed. The AUC of the PLMR scale was 0.94 in Mtp-1 and 0.87 in Mtp-2. In both cohorts, the PLMR outperformed CSF Aβ42 or Aβ42/40 ratio. The diagnostic performance was improved with the PLMR with an NRI equal to 44.3% in Mtp-1 and 28.8% in Mtp-2.Conclusion: The integration of the Aβ42/Aβ40 ratio in the PLMR scale resulted in an easy-to-use tool which reduced the discrepancies in biologically doubtful cases and increased the confidence in the diagnosis in memory center. |
| first_indexed | 2024-12-22T09:42:40Z |
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| institution | Directory Open Access Journal |
| issn | 1663-4365 |
| language | English |
| last_indexed | 2024-12-22T09:42:40Z |
| publishDate | 2018-05-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Aging Neuroscience |
| spelling | doaj.art-ad80b40a8fb742abb4f089e76dce60d72022-12-21T18:30:38ZengFrontiers Media S.A.Frontiers in Aging Neuroscience1663-43652018-05-011010.3389/fnagi.2018.00138325959Relevance of Aβ42/40 Ratio for Detection of Alzheimer Disease Pathology in Clinical Routine: The PLMR ScaleSylvain Lehmann0Sylvain Lehmann1Constance Delaby2Constance Delaby3Guilaine Boursier4Cindy Catteau5Nelly Ginestet6Laurent Tiers7Aleksandra Maceski8Sophie Navucet9Claire Paquet10Julien Dumurgier11Eugeen Vanmechelen12Hugo Vanderstichele13Audrey Gabelle14Audrey Gabelle15Audrey Gabelle16Laboratoire de Biochimie Protéomique Clinique, Institute of Regenerative Medicine and Biotherapies, Centre Hospitalier Universitaire de Montpellier, Montpellier, FranceUniversité de Montpellier, Montpellier, FranceLaboratoire de Biochimie Protéomique Clinique, Institute of Regenerative Medicine and Biotherapies, Centre Hospitalier Universitaire de Montpellier, Montpellier, FranceUniversité de Montpellier, Montpellier, FranceLaboratoire de Biochimie Protéomique Clinique, Institute of Regenerative Medicine and Biotherapies, Centre Hospitalier Universitaire de Montpellier, Montpellier, FranceLaboratoire de Biochimie Protéomique Clinique, Institute of Regenerative Medicine and Biotherapies, Centre Hospitalier Universitaire de Montpellier, Montpellier, FranceLaboratoire de Biochimie Protéomique Clinique, Institute of Regenerative Medicine and Biotherapies, Centre Hospitalier Universitaire de Montpellier, Montpellier, FranceLaboratoire de Biochimie Protéomique Clinique, Institute of Regenerative Medicine and Biotherapies, Centre Hospitalier Universitaire de Montpellier, Montpellier, FranceLaboratoire de Biochimie Protéomique Clinique, Institute of Regenerative Medicine and Biotherapies, Centre Hospitalier Universitaire de Montpellier, Montpellier, FranceDépartement de Neurologie, Centre Mémoire de Ressources et de Recherche de Montpellier, Montpellier University Hospital, Centre Hospitalier Universitaire de Montpellier, Montpellier, FranceGroupe Hospitalier Lariboisière Fernand-Widal, INSERM U942, Centre de Neurologie Cognitive, Université Paris Diderot, Paris, FranceGroupe Hospitalier Lariboisière Fernand-Widal, INSERM U942, Centre de Neurologie Cognitive, Université Paris Diderot, Paris, FranceADx NeuroSciences, Ghent, BelgiumADx NeuroSciences, Ghent, BelgiumLaboratoire de Biochimie Protéomique Clinique, Institute of Regenerative Medicine and Biotherapies, Centre Hospitalier Universitaire de Montpellier, Montpellier, FranceUniversité de Montpellier, Montpellier, FranceDépartement de Neurologie, Centre Mémoire de Ressources et de Recherche de Montpellier, Montpellier University Hospital, Centre Hospitalier Universitaire de Montpellier, Montpellier, FranceBackground: Cerebrospinal fluid (CSF) biomarkers (Aβ peptides and tau proteins) improved the diagnosis of Alzheimer’s disease (AD) in research and clinical settings. We previously described the PLM-scale (Paris-Lille-Montpellier study), which combines Aβ42, tau, and phosphorylated ptau(181) biomarkers in an easy to use and clinically relevant way. The purpose of this work is to evaluate an optimized PLMR-scale (PLM ratio scale) that now includes the Aβ42/Aβ40 ratio to detect AD versus non-AD (NAD) participants in clinical routine of memory centers.Methods: Both scales were compared using 904 participants with cognitive impairment recruited from two independent cohorts (Mtp-1 and Mtp-2). The CSF Aβ42/Aβ40 ratio was measured systematically in Mtp-1, and only on biologically discordant cases in Mtp-2. Two different ELISA kit providers were also employed. The distribution of AD and NAD patients and the discrepancies of biomarker profiles were computed. Receiver Operating Characteristic curves were used to represent clinical sensitivity and specificity for AD detection. The classification of patients with the net reclassification index (NRI) was also evaluated.Results: Nine hundred and four participants (342 AD and 562 NAD) were studied; 400 in Mtp-1 and 504 in Mtp-2. For AD patients, the mean CSF Aβ42 and CSF Aβ42/40 ratio was 553 ± 216 pg/mL and 0.069 ± 0.022 pg/mL in Mtp-1 and 702 ± 335 pg/mL and 0.045 ± 0.020 pg/mL in Mtp-2. The distribution of AD and NAD differed between the PLM and the PLMR scales (p < 0.0001). The percentage AD well-classified (class 3) increased with PLMR from 38 to 83% in Mpt-1 and from 33 to 53% in Mpt-2. A sharp reduction of the discordant profiles going from 34 to 16.3% and from 37.5 to 19.8%, for Mtp-1 and Mtp-2 respectively, was also observed. The AUC of the PLMR scale was 0.94 in Mtp-1 and 0.87 in Mtp-2. In both cohorts, the PLMR outperformed CSF Aβ42 or Aβ42/40 ratio. The diagnostic performance was improved with the PLMR with an NRI equal to 44.3% in Mtp-1 and 28.8% in Mtp-2.Conclusion: The integration of the Aβ42/Aβ40 ratio in the PLMR scale resulted in an easy-to-use tool which reduced the discrepancies in biologically doubtful cases and increased the confidence in the diagnosis in memory center.https://www.frontiersin.org/article/10.3389/fnagi.2018.00138/fullAlzheimer’s diseasebiomarkerscerebrospinal fluid (CSF)screening scale |
| spellingShingle | Sylvain Lehmann Sylvain Lehmann Constance Delaby Constance Delaby Guilaine Boursier Cindy Catteau Nelly Ginestet Laurent Tiers Aleksandra Maceski Sophie Navucet Claire Paquet Julien Dumurgier Eugeen Vanmechelen Hugo Vanderstichele Audrey Gabelle Audrey Gabelle Audrey Gabelle Relevance of Aβ42/40 Ratio for Detection of Alzheimer Disease Pathology in Clinical Routine: The PLMR Scale Frontiers in Aging Neuroscience Alzheimer’s disease biomarkers cerebrospinal fluid (CSF) screening scale |
| title | Relevance of Aβ42/40 Ratio for Detection of Alzheimer Disease Pathology in Clinical Routine: The PLMR Scale |
| title_full | Relevance of Aβ42/40 Ratio for Detection of Alzheimer Disease Pathology in Clinical Routine: The PLMR Scale |
| title_fullStr | Relevance of Aβ42/40 Ratio for Detection of Alzheimer Disease Pathology in Clinical Routine: The PLMR Scale |
| title_full_unstemmed | Relevance of Aβ42/40 Ratio for Detection of Alzheimer Disease Pathology in Clinical Routine: The PLMR Scale |
| title_short | Relevance of Aβ42/40 Ratio for Detection of Alzheimer Disease Pathology in Clinical Routine: The PLMR Scale |
| title_sort | relevance of aβ42 40 ratio for detection of alzheimer disease pathology in clinical routine the plmr scale |
| topic | Alzheimer’s disease biomarkers cerebrospinal fluid (CSF) screening scale |
| url | https://www.frontiersin.org/article/10.3389/fnagi.2018.00138/full |
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