High-precision plasma β-amyloid 42/40 predicts current and future brain amyloidosis
OBJECTIVEWe examined whether plasma β-amyloid (Aβ)42/Aβ40, as measured by a high-precision assay, accurately diagnosed brain amyloidosis using amyloid PET or CSF p-tau181/Aβ42 as reference standards. METHODSUsing an immunoprecipitation and liquid chromatography–mass spectrometry assay, we measured A...
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| Veröffentlicht in: | Neurology 2019-10, Vol.93 (17), p.e1647-e1659 |
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| creator | Schindler, Suzanne E Bollinger, James G Ovod, Vitaliy Mawuenyega, Kwasi G Li, Yan Gordon, Brian A Holtzman, David M Morris, John C Benzinger, Tammie L.S Xiong, Chengjie Fagan, Anne M Bateman, Randall J |
| description | OBJECTIVEWe examined whether plasma β-amyloid (Aβ)42/Aβ40, as measured by a high-precision assay, accurately diagnosed brain amyloidosis using amyloid PET or CSF p-tau181/Aβ42 as reference standards.
METHODSUsing an immunoprecipitation and liquid chromatography–mass spectrometry assay, we measured Aβ42/Aβ40 in plasma and CSF samples from 158 mostly cognitively normal individuals that were collected within 18 months of an amyloid PET scan.
RESULTSPlasma Aβ42/Aβ40 had a high correspondence with amyloid PET status (receiver operating characteristic area under the curve [AUC] 0.88, 95% confidence interval [CI] 0.82–0.93) and CSF p-tau181/Aβ42 (AUC 0.85, 95% CI 0.79–0.92). The combination of plasma Aβ42/Aβ40, age, and APOE ε4 status had a very high correspondence with amyloid PET (AUC 0.94, 95% CI 0.90–0.97). Individuals with a negative amyloid PET scan at baseline and a positive plasma Aβ42/Aβ40 ( |
| doi_str_mv | 10.1212/WNL.0000000000008081 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_pubme</sourceid><recordid>TN_cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_6946467</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>2268317423</sourcerecordid><originalsourceid>FETCH-LOGICAL-c5081-297d66f5d292525f3ca4b94f00e98ac07b4557e517030686c5902e2fdeb851d23</originalsourceid><addsrcrecordid>eNp9kc1O3DAUha2qVZlC3wBVXnYT8L-dDRJC_Ekj2IBgZzmOw5g68WAnjHgtHoRnwtVMEbDo3dzF_c65RzoA7GK0hwkm-zcX8z30bhRS-AuYYU5EJSi5_QpmCBFVUSXVFviR8z1C5Sjr72CLYioxF_UMXJ35u0W1TM767OMAl8Hk3sCX58r0TyH6FjKyzxAsROvtmKGdUnLDCM3Qwm4ap-Rgk4wf4IaP2ecd8K0zIbufm70Nrk-Or47Oqvnl6fnR4byyvIStSC1bITrekppwwjtqDWtq1iHkamUskg3jXDqOJaJIKGF5jYgjXesaxXFL6DY4WPsup6Z3rS25kgl6mXxv0pOOxuuPl8Ev9F181KJmgglZDH5vDFJ8mFwede-zdSGYwcUpa0KEolgyQgvK1qhNMefkurc3GOm_hehSiP5cSJH9eh_xTfSvgQKoNbCKYXQp_wnTyiW9cCaMi_97vwLc_Jhf</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>2268317423</pqid></control><display><type>article</type><title>High-precision plasma β-amyloid 42/40 predicts current and future brain amyloidosis</title><source>MEDLINE</source><source>Alma/SFX Local Collection</source><source>Journals@Ovid Complete</source><creator>Schindler, Suzanne E ; Bollinger, James G ; Ovod, Vitaliy ; Mawuenyega, Kwasi G ; Li, Yan ; Gordon, Brian A ; Holtzman, David M ; Morris, John C ; Benzinger, Tammie L.S ; Xiong, Chengjie ; Fagan, Anne M ; Bateman, Randall J</creator><creatorcontrib>Schindler, Suzanne E ; Bollinger, James G ; Ovod, Vitaliy ; Mawuenyega, Kwasi G ; Li, Yan ; Gordon, Brian A ; Holtzman, David M ; Morris, John C ; Benzinger, Tammie L.S ; Xiong, Chengjie ; Fagan, Anne M ; Bateman, Randall J</creatorcontrib><description>OBJECTIVEWe examined whether plasma β-amyloid (Aβ)42/Aβ40, as measured by a high-precision assay, accurately diagnosed brain amyloidosis using amyloid PET or CSF p-tau181/Aβ42 as reference standards.
METHODSUsing an immunoprecipitation and liquid chromatography–mass spectrometry assay, we measured Aβ42/Aβ40 in plasma and CSF samples from 158 mostly cognitively normal individuals that were collected within 18 months of an amyloid PET scan.
RESULTSPlasma Aβ42/Aβ40 had a high correspondence with amyloid PET status (receiver operating characteristic area under the curve [AUC] 0.88, 95% confidence interval [CI] 0.82–0.93) and CSF p-tau181/Aβ42 (AUC 0.85, 95% CI 0.79–0.92). The combination of plasma Aβ42/Aβ40, age, and APOE ε4 status had a very high correspondence with amyloid PET (AUC 0.94, 95% CI 0.90–0.97). Individuals with a negative amyloid PET scan at baseline and a positive plasma Aβ42/Aβ40 (<0.1218) had a 15-fold greater risk of conversion to amyloid PET-positive compared to individuals with a negative plasma Aβ42/Aβ40 (p = 0.01).
CONCLUSIONSPlasma Aβ42/Aβ40, especially when combined with age and APOE ε4 status, accurately diagnoses brain amyloidosis and can be used to screen cognitively normal individuals for brain amyloidosis. Individuals with a negative amyloid PET scan and positive plasma Aβ42/Aβ40 are at increased risk for converting to amyloid PET-positive. Plasma Aβ42/Aβ40 could be used in prevention trials to screen for individuals likely to be amyloid PET-positive and at risk for Alzheimer disease dementia.
CLASSIFICATION OF EVIDENCEThis study provides Class II evidence that plasma Aβ42/Aβ40 levels accurately determine amyloid PET status in cognitively normal research participants.</description><identifier>ISSN: 0028-3878</identifier><identifier>EISSN: 1526-632X</identifier><identifier>DOI: 10.1212/WNL.0000000000008081</identifier><identifier>PMID: 31371569</identifier><language>eng</language><publisher>United States: American Academy of Neurology</publisher><subject>Age Factors ; Aged ; Amyloid beta-Peptides - blood ; Amyloid beta-Peptides - cerebrospinal fluid ; Amyloidosis - blood ; Amyloidosis - diagnostic imaging ; Amyloidosis - genetics ; Apolipoprotein E4 - genetics ; Biomarkers - blood ; Brain - diagnostic imaging ; Brain - metabolism ; Female ; Humans ; Longitudinal Studies ; Male ; Middle Aged ; Peptide Fragments - blood ; Peptide Fragments - cerebrospinal fluid ; Positron-Emission Tomography ; Prognosis ; tau Proteins - cerebrospinal fluid</subject><ispartof>Neurology, 2019-10, Vol.93 (17), p.e1647-e1659</ispartof><rights>2019 American Academy of Neurology</rights><rights>2019 American Academy of Neurology.</rights><rights>2019 American Academy of Neurology 2019 American Academy of Neurology</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c5081-297d66f5d292525f3ca4b94f00e98ac07b4557e517030686c5902e2fdeb851d23</citedby><cites>FETCH-LOGICAL-c5081-297d66f5d292525f3ca4b94f00e98ac07b4557e517030686c5902e2fdeb851d23</cites><orcidid>0000-0002-7729-1702</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>230,314,776,780,881,27901,27902</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/31371569$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Schindler, Suzanne E</creatorcontrib><creatorcontrib>Bollinger, James G</creatorcontrib><creatorcontrib>Ovod, Vitaliy</creatorcontrib><creatorcontrib>Mawuenyega, Kwasi G</creatorcontrib><creatorcontrib>Li, Yan</creatorcontrib><creatorcontrib>Gordon, Brian A</creatorcontrib><creatorcontrib>Holtzman, David M</creatorcontrib><creatorcontrib>Morris, John C</creatorcontrib><creatorcontrib>Benzinger, Tammie L.S</creatorcontrib><creatorcontrib>Xiong, Chengjie</creatorcontrib><creatorcontrib>Fagan, Anne M</creatorcontrib><creatorcontrib>Bateman, Randall J</creatorcontrib><title>High-precision plasma β-amyloid 42/40 predicts current and future brain amyloidosis</title><title>Neurology</title><addtitle>Neurology</addtitle><description>OBJECTIVEWe examined whether plasma β-amyloid (Aβ)42/Aβ40, as measured by a high-precision assay, accurately diagnosed brain amyloidosis using amyloid PET or CSF p-tau181/Aβ42 as reference standards.
METHODSUsing an immunoprecipitation and liquid chromatography–mass spectrometry assay, we measured Aβ42/Aβ40 in plasma and CSF samples from 158 mostly cognitively normal individuals that were collected within 18 months of an amyloid PET scan.
RESULTSPlasma Aβ42/Aβ40 had a high correspondence with amyloid PET status (receiver operating characteristic area under the curve [AUC] 0.88, 95% confidence interval [CI] 0.82–0.93) and CSF p-tau181/Aβ42 (AUC 0.85, 95% CI 0.79–0.92). The combination of plasma Aβ42/Aβ40, age, and APOE ε4 status had a very high correspondence with amyloid PET (AUC 0.94, 95% CI 0.90–0.97). Individuals with a negative amyloid PET scan at baseline and a positive plasma Aβ42/Aβ40 (<0.1218) had a 15-fold greater risk of conversion to amyloid PET-positive compared to individuals with a negative plasma Aβ42/Aβ40 (p = 0.01).
CONCLUSIONSPlasma Aβ42/Aβ40, especially when combined with age and APOE ε4 status, accurately diagnoses brain amyloidosis and can be used to screen cognitively normal individuals for brain amyloidosis. Individuals with a negative amyloid PET scan and positive plasma Aβ42/Aβ40 are at increased risk for converting to amyloid PET-positive. Plasma Aβ42/Aβ40 could be used in prevention trials to screen for individuals likely to be amyloid PET-positive and at risk for Alzheimer disease dementia.
CLASSIFICATION OF EVIDENCEThis study provides Class II evidence that plasma Aβ42/Aβ40 levels accurately determine amyloid PET status in cognitively normal research participants.</description><subject>Age Factors</subject><subject>Aged</subject><subject>Amyloid beta-Peptides - blood</subject><subject>Amyloid beta-Peptides - cerebrospinal fluid</subject><subject>Amyloidosis - blood</subject><subject>Amyloidosis - diagnostic imaging</subject><subject>Amyloidosis - genetics</subject><subject>Apolipoprotein E4 - genetics</subject><subject>Biomarkers - blood</subject><subject>Brain - diagnostic imaging</subject><subject>Brain - metabolism</subject><subject>Female</subject><subject>Humans</subject><subject>Longitudinal Studies</subject><subject>Male</subject><subject>Middle Aged</subject><subject>Peptide Fragments - blood</subject><subject>Peptide Fragments - cerebrospinal fluid</subject><subject>Positron-Emission Tomography</subject><subject>Prognosis</subject><subject>tau Proteins - cerebrospinal fluid</subject><issn>0028-3878</issn><issn>1526-632X</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2019</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kc1O3DAUha2qVZlC3wBVXnYT8L-dDRJC_Ekj2IBgZzmOw5g68WAnjHgtHoRnwtVMEbDo3dzF_c65RzoA7GK0hwkm-zcX8z30bhRS-AuYYU5EJSi5_QpmCBFVUSXVFviR8z1C5Sjr72CLYioxF_UMXJ35u0W1TM767OMAl8Hk3sCX58r0TyH6FjKyzxAsROvtmKGdUnLDCM3Qwm4ap-Rgk4wf4IaP2ecd8K0zIbufm70Nrk-Or47Oqvnl6fnR4byyvIStSC1bITrekppwwjtqDWtq1iHkamUskg3jXDqOJaJIKGF5jYgjXesaxXFL6DY4WPsup6Z3rS25kgl6mXxv0pOOxuuPl8Ev9F181KJmgglZDH5vDFJ8mFwede-zdSGYwcUpa0KEolgyQgvK1qhNMefkurc3GOm_hehSiP5cSJH9eh_xTfSvgQKoNbCKYXQp_wnTyiW9cCaMi_97vwLc_Jhf</recordid><startdate>20191022</startdate><enddate>20191022</enddate><creator>Schindler, Suzanne E</creator><creator>Bollinger, James G</creator><creator>Ovod, Vitaliy</creator><creator>Mawuenyega, Kwasi G</creator><creator>Li, Yan</creator><creator>Gordon, Brian A</creator><creator>Holtzman, David M</creator><creator>Morris, John C</creator><creator>Benzinger, Tammie L.S</creator><creator>Xiong, Chengjie</creator><creator>Fagan, Anne M</creator><creator>Bateman, Randall J</creator><general>American Academy of Neurology</general><general>Lippincott Williams & Wilkins</general><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/0000-0002-7729-1702</orcidid></search><sort><creationdate>20191022</creationdate><title>High-precision plasma β-amyloid 42/40 predicts current and future brain amyloidosis</title><author>Schindler, Suzanne E ; Bollinger, James G ; Ovod, Vitaliy ; Mawuenyega, Kwasi G ; Li, Yan ; Gordon, Brian A ; Holtzman, David M ; Morris, John C ; Benzinger, Tammie L.S ; Xiong, Chengjie ; Fagan, Anne M ; Bateman, Randall J</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c5081-297d66f5d292525f3ca4b94f00e98ac07b4557e517030686c5902e2fdeb851d23</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2019</creationdate><topic>Age Factors</topic><topic>Aged</topic><topic>Amyloid beta-Peptides - blood</topic><topic>Amyloid beta-Peptides - cerebrospinal fluid</topic><topic>Amyloidosis - blood</topic><topic>Amyloidosis - diagnostic imaging</topic><topic>Amyloidosis - genetics</topic><topic>Apolipoprotein E4 - genetics</topic><topic>Biomarkers - blood</topic><topic>Brain - diagnostic imaging</topic><topic>Brain - metabolism</topic><topic>Female</topic><topic>Humans</topic><topic>Longitudinal Studies</topic><topic>Male</topic><topic>Middle Aged</topic><topic>Peptide Fragments - blood</topic><topic>Peptide Fragments - cerebrospinal fluid</topic><topic>Positron-Emission Tomography</topic><topic>Prognosis</topic><topic>tau Proteins - cerebrospinal fluid</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Schindler, Suzanne E</creatorcontrib><creatorcontrib>Bollinger, James G</creatorcontrib><creatorcontrib>Ovod, Vitaliy</creatorcontrib><creatorcontrib>Mawuenyega, Kwasi G</creatorcontrib><creatorcontrib>Li, Yan</creatorcontrib><creatorcontrib>Gordon, Brian A</creatorcontrib><creatorcontrib>Holtzman, David M</creatorcontrib><creatorcontrib>Morris, John C</creatorcontrib><creatorcontrib>Benzinger, Tammie L.S</creatorcontrib><creatorcontrib>Xiong, Chengjie</creatorcontrib><creatorcontrib>Fagan, Anne M</creatorcontrib><creatorcontrib>Bateman, Randall J</creatorcontrib><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>Neurology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Schindler, Suzanne E</au><au>Bollinger, James G</au><au>Ovod, Vitaliy</au><au>Mawuenyega, Kwasi G</au><au>Li, Yan</au><au>Gordon, Brian A</au><au>Holtzman, David M</au><au>Morris, John C</au><au>Benzinger, Tammie L.S</au><au>Xiong, Chengjie</au><au>Fagan, Anne M</au><au>Bateman, Randall J</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>High-precision plasma β-amyloid 42/40 predicts current and future brain amyloidosis</atitle><jtitle>Neurology</jtitle><addtitle>Neurology</addtitle><date>2019-10-22</date><risdate>2019</risdate><volume>93</volume><issue>17</issue><spage>e1647</spage><epage>e1659</epage><pages>e1647-e1659</pages><issn>0028-3878</issn><eissn>1526-632X</eissn><abstract>OBJECTIVEWe examined whether plasma β-amyloid (Aβ)42/Aβ40, as measured by a high-precision assay, accurately diagnosed brain amyloidosis using amyloid PET or CSF p-tau181/Aβ42 as reference standards.
METHODSUsing an immunoprecipitation and liquid chromatography–mass spectrometry assay, we measured Aβ42/Aβ40 in plasma and CSF samples from 158 mostly cognitively normal individuals that were collected within 18 months of an amyloid PET scan.
RESULTSPlasma Aβ42/Aβ40 had a high correspondence with amyloid PET status (receiver operating characteristic area under the curve [AUC] 0.88, 95% confidence interval [CI] 0.82–0.93) and CSF p-tau181/Aβ42 (AUC 0.85, 95% CI 0.79–0.92). The combination of plasma Aβ42/Aβ40, age, and APOE ε4 status had a very high correspondence with amyloid PET (AUC 0.94, 95% CI 0.90–0.97). Individuals with a negative amyloid PET scan at baseline and a positive plasma Aβ42/Aβ40 (<0.1218) had a 15-fold greater risk of conversion to amyloid PET-positive compared to individuals with a negative plasma Aβ42/Aβ40 (p = 0.01).
CONCLUSIONSPlasma Aβ42/Aβ40, especially when combined with age and APOE ε4 status, accurately diagnoses brain amyloidosis and can be used to screen cognitively normal individuals for brain amyloidosis. Individuals with a negative amyloid PET scan and positive plasma Aβ42/Aβ40 are at increased risk for converting to amyloid PET-positive. Plasma Aβ42/Aβ40 could be used in prevention trials to screen for individuals likely to be amyloid PET-positive and at risk for Alzheimer disease dementia.
CLASSIFICATION OF EVIDENCEThis study provides Class II evidence that plasma Aβ42/Aβ40 levels accurately determine amyloid PET status in cognitively normal research participants.</abstract><cop>United States</cop><pub>American Academy of Neurology</pub><pmid>31371569</pmid><doi>10.1212/WNL.0000000000008081</doi><orcidid>https://orcid.org/0000-0002-7729-1702</orcidid><oa>free_for_read</oa></addata></record> |
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| subjects | Age Factors Aged Amyloid beta-Peptides - blood Amyloid beta-Peptides - cerebrospinal fluid Amyloidosis - blood Amyloidosis - diagnostic imaging Amyloidosis - genetics Apolipoprotein E4 - genetics Biomarkers - blood Brain - diagnostic imaging Brain - metabolism Female Humans Longitudinal Studies Male Middle Aged Peptide Fragments - blood Peptide Fragments - cerebrospinal fluid Positron-Emission Tomography Prognosis tau Proteins - cerebrospinal fluid |
| title | High-precision plasma β-amyloid 42/40 predicts current and future brain amyloidosis |
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