Blood biomarkers indicate that the preclinical stages of Alzheimer's disease present overlapping molecular features
It is still debated whether non-specific preclinical symptoms of Alzheimer’s disease (AD) can have diagnostic relevance. We followed the evolution from cognitively normal to AD by NMR-based metabolomics of blood sera. Multivariate statistical analysis of the NMR profiles yielded models that discrimi...
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description | It is still debated whether non-specific preclinical symptoms of Alzheimer’s disease (AD) can have diagnostic relevance. We followed the evolution from cognitively normal to AD by NMR-based metabolomics of blood sera. Multivariate statistical analysis of the NMR profiles yielded models that discriminated subjective memory decline (SMD), mild cognitive impairment (MCI) and AD. We validated a panel of six statistically significant metabolites that predicted SMD, MCI and AD in a blind cohort with sensitivity values ranging from 88 to 95% and receiver operating characteristic values from 0.88 to 0.99. However, lower values of specificity, accuracy and precision were observed for the models involving SMD and MCI, which is in line with the pathological heterogeneity indicated by clinical data. This excludes a “linear” molecular evolution of the pathology, pointing to the presence of overlapping “gray-zones” due to the reciprocal interference of the intermediate stages. Yet, the clear difference observed in the metabolic pathways of each model suggests that pathway dysregulations could be investigated for diagnostic purposes. |
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We followed the evolution from cognitively normal to AD by NMR-based metabolomics of blood sera. Multivariate statistical analysis of the NMR profiles yielded models that discriminated subjective memory decline (SMD), mild cognitive impairment (MCI) and AD. We validated a panel of six statistically significant metabolites that predicted SMD, MCI and AD in a blind cohort with sensitivity values ranging from 88 to 95% and receiver operating characteristic values from 0.88 to 0.99. However, lower values of specificity, accuracy and precision were observed for the models involving SMD and MCI, which is in line with the pathological heterogeneity indicated by clinical data. This excludes a “linear” molecular evolution of the pathology, pointing to the presence of overlapping “gray-zones” due to the reciprocal interference of the intermediate stages. 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We followed the evolution from cognitively normal to AD by NMR-based metabolomics of blood sera. Multivariate statistical analysis of the NMR profiles yielded models that discriminated subjective memory decline (SMD), mild cognitive impairment (MCI) and AD. We validated a panel of six statistically significant metabolites that predicted SMD, MCI and AD in a blind cohort with sensitivity values ranging from 88 to 95% and receiver operating characteristic values from 0.88 to 0.99. However, lower values of specificity, accuracy and precision were observed for the models involving SMD and MCI, which is in line with the pathological heterogeneity indicated by clinical data. This excludes a “linear” molecular evolution of the pathology, pointing to the presence of overlapping “gray-zones” due to the reciprocal interference of the intermediate stages. Yet, the clear difference observed in the metabolic pathways of each model suggests that pathway dysregulations could be investigated for diagnostic purposes.</description><subject>692/4017</subject><subject>692/53/2423</subject><subject>Aged</subject><subject>Alzheimer Disease - blood</subject><subject>Alzheimer Disease - classification</subject><subject>Alzheimer Disease - pathology</subject><subject>Biomarkers - blood</subject><subject>Cognitive Dysfunction - blood</subject><subject>Cognitive Dysfunction - pathology</subject><subject>Disease Progression</subject><subject>Female</subject><subject>Humanities and Social Sciences</subject><subject>Humans</subject><subject>Magnetic Resonance Imaging</subject><subject>Male</subject><subject>Middle Aged</subject><subject>multidisciplinary</subject><subject>ROC Curve</subject><subject>Science</subject><subject>Science (multidisciplinary)</subject><issn>2045-2322</issn><issn>2045-2322</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2020</creationdate><recordtype>article</recordtype><sourceid>C6C</sourceid><sourceid>EIF</sourceid><recordid>eNp9kctu1TAQhiNERavSF-gCeQebgC_xbYNUKm5SJTbt2vJxJue4OHHwJJUOT1_TU6qywQt75Pnm94z_pjln9D2jwnzAjklrWsppq5kRvN2_aE447WTLBecvn8XHzRniLa1Lctsx-6o5FtxqwbQ9afBTyrknm5hHX35CQRKnPga_AFl2fqkbkLlASHGqt4ng4reAJA_kIv3eQRyhvEXSRwSPDyTCtJB8ByX5eY7Tlow5QViTL2QAv6yVeN0cDT4hnD2ep83Nl8_Xl9_aqx9fv19eXLWh69TSDr0OvaRMB2s2gmor68jSBKWppMZY6gVQzXwnghqo9MB76aVWlDOrwHhx2nw86M7rZoQ-1M6KT24usc66d9lH929miju3zXdOSyaNUlXg3aNAyb9WwMWNEQOk5CfIKzpe-1RKKmYryg9oKBmxwPD0DKPuj2HuYJirhrkHw9y-Fr153uBTyV97KiAOANbUtIXibvNapvpp_5O9B8ZwpCg</recordid><startdate>20200924</startdate><enddate>20200924</enddate><creator>Di Costanzo, Alfonso</creator><creator>Paris, Debora</creator><creator>Melck, Dominique</creator><creator>Angiolillo, Antonella</creator><creator>Corso, Gaetano</creator><creator>Maniscalco, Mauro</creator><creator>Motta, Andrea</creator><general>Nature Publishing Group UK</general><scope>C6C</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope><scope>5PM</scope><orcidid>https://orcid.org/0000-0002-8643-658X</orcidid><orcidid>https://orcid.org/0000-0001-6751-9921</orcidid></search><sort><creationdate>20200924</creationdate><title>Blood biomarkers indicate that the preclinical stages of Alzheimer's disease present overlapping molecular features</title><author>Di Costanzo, Alfonso ; Paris, Debora ; Melck, Dominique ; Angiolillo, Antonella ; Corso, Gaetano ; Maniscalco, Mauro ; Motta, Andrea</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c446t-fd7cd5017c98b3079541558c670508890a3e071a43c6f05ae2d5a57602196e8a3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2020</creationdate><topic>692/4017</topic><topic>692/53/2423</topic><topic>Aged</topic><topic>Alzheimer Disease - blood</topic><topic>Alzheimer Disease - classification</topic><topic>Alzheimer Disease - pathology</topic><topic>Biomarkers - blood</topic><topic>Cognitive Dysfunction - blood</topic><topic>Cognitive Dysfunction - pathology</topic><topic>Disease Progression</topic><topic>Female</topic><topic>Humanities and Social Sciences</topic><topic>Humans</topic><topic>Magnetic Resonance Imaging</topic><topic>Male</topic><topic>Middle Aged</topic><topic>multidisciplinary</topic><topic>ROC Curve</topic><topic>Science</topic><topic>Science (multidisciplinary)</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Di Costanzo, Alfonso</creatorcontrib><creatorcontrib>Paris, Debora</creatorcontrib><creatorcontrib>Melck, Dominique</creatorcontrib><creatorcontrib>Angiolillo, Antonella</creatorcontrib><creatorcontrib>Corso, Gaetano</creatorcontrib><creatorcontrib>Maniscalco, Mauro</creatorcontrib><creatorcontrib>Motta, Andrea</creatorcontrib><collection>Springer Nature OA Free Journals</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Scientific reports</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Di Costanzo, Alfonso</au><au>Paris, Debora</au><au>Melck, Dominique</au><au>Angiolillo, Antonella</au><au>Corso, Gaetano</au><au>Maniscalco, Mauro</au><au>Motta, Andrea</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Blood biomarkers indicate that the preclinical stages of Alzheimer's disease present overlapping molecular features</atitle><jtitle>Scientific reports</jtitle><stitle>Sci Rep</stitle><addtitle>Sci Rep</addtitle><date>2020-09-24</date><risdate>2020</risdate><volume>10</volume><issue>1</issue><spage>15612</spage><epage>15612</epage><pages>15612-15612</pages><artnum>15612</artnum><issn>2045-2322</issn><eissn>2045-2322</eissn><abstract>It is still debated whether non-specific preclinical symptoms of Alzheimer’s disease (AD) can have diagnostic relevance. We followed the evolution from cognitively normal to AD by NMR-based metabolomics of blood sera. Multivariate statistical analysis of the NMR profiles yielded models that discriminated subjective memory decline (SMD), mild cognitive impairment (MCI) and AD. We validated a panel of six statistically significant metabolites that predicted SMD, MCI and AD in a blind cohort with sensitivity values ranging from 88 to 95% and receiver operating characteristic values from 0.88 to 0.99. However, lower values of specificity, accuracy and precision were observed for the models involving SMD and MCI, which is in line with the pathological heterogeneity indicated by clinical data. This excludes a “linear” molecular evolution of the pathology, pointing to the presence of overlapping “gray-zones” due to the reciprocal interference of the intermediate stages. 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subjects | 692/4017 692/53/2423 Aged Alzheimer Disease - blood Alzheimer Disease - classification Alzheimer Disease - pathology Biomarkers - blood Cognitive Dysfunction - blood Cognitive Dysfunction - pathology Disease Progression Female Humanities and Social Sciences Humans Magnetic Resonance Imaging Male Middle Aged multidisciplinary ROC Curve Science Science (multidisciplinary) |
title | Blood biomarkers indicate that the preclinical stages of Alzheimer's disease present overlapping molecular features |
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