{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Rissman RA"],"funding":["NIA NIH HHS","NINDS NIH HHS"],"pagination":["1214-1224"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC10916957"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["20(2)"],"pubmed_abstract":["<h4>Introduction</h4>Incorporating blood-based Alzheimer's disease biomarkers such as tau and amyloid beta (Aβ) into screening algorithms may improve screening efficiency.<h4>Methods</h4>Plasma Aβ, phosphorylated tau (p-tau)181, and p-tau217 concentration levels from AHEAD 3-45 study participants were measured using mass spectrometry. Tau concentration ratios for each proteoform were calculated to normalize for inter-individual differences. Receiver operating characteristic (ROC) curve analysis was performed for each biomarker against amyloid positivity, defined by > 20 Centiloids. Mixture of experts analysis assessed the value of including tau concentration ratios into the existing predictive algorithm for amyloid positron emission tomography status.<h4>Results</h4>The area under the receiver operating curve (AUC) was 0.87 for Aβ42/Aβ40, 0.74 for phosphorylated variant p-tau181 ratio (p-tau181/np-tau181), and 0.92 for phosphorylated variant p-tau217 ratio (p-tau217/np-tau217). The Plasma Predicted Centiloid (PPC), a predictive model including p-tau217/np-tau217, Aβ42/Aβ40, age, and apolipoprotein E improved AUC to 0.95.<h4>Discussion</h4>Including plasma p-tau217/np-tau217 along with Aβ42/Aβ40 in predictive algorithms may streamline screening preclinical individuals into anti-amyloid clinical trials.<h4>Clinicaltrials</h4>gov Identifier: NCT04468659 HIGHLIGHTS: The addition of plasma phosphorylated variant p-tau217 ratio (p-tau217/np-tau217) significantly improved plasma biomarker algorithms for identifying preclinical amyloid positron emission tomography positivity. Prediction performance at higher NAV Centiloid levels was improved with p-tau217/np-tau217. All models generated for this study are incorporated into the Plasma Predicted Centiloid (PPC) app for public use."],"journal":["Alzheimer's & dementia : the journal of the Alzheimer's Association"],"pubmed_title":["Plasma Aβ42/Aβ40 and phospho-tau217 concentration ratios increase the accuracy of amyloid PET classification in preclinical Alzheimer's disease."],"pmcid":["PMC10916957"],"funding_grant_id":["R01 AG061848","RF1 AG073979","U24 AG057437","U19 AG078109","R01 AG053798","R01 AG050595","R01 AG054029","R01 AG058533","R01 AG018440","R37 AG018440","K99 AG070390","R01 AG073979","R25 NS117367","P30 AG066530","R56 AG058533","R01 AG058252","R44 AG059489"],"pubmed_authors":["Sachdev P","Yarasheski KE","Langford O","Ngolab J","Braunstein JB","Rafii MS","Jimenez-Maggiora G","AHEAD 3-45 Study team","Raman R","Donohue MC","Abdel-Latif S","Kirmess KM","Johnson KA","Aisen PS","Sperling RA","Wente-Roth T","Rissman RA","West T","Meyer MR","Winston CN","Irizarry M"],"additional_accession":[]},"is_claimable":false,"name":"Plasma Aβ42/Aβ40 and phospho-tau217 concentration ratios increase the accuracy of amyloid PET classification in preclinical Alzheimer's disease.","description":"<h4>Introduction</h4>Incorporating blood-based Alzheimer's disease biomarkers such as tau and amyloid beta (Aβ) into screening algorithms may improve screening efficiency.<h4>Methods</h4>Plasma Aβ, phosphorylated tau (p-tau)181, and p-tau217 concentration levels from AHEAD 3-45 study participants were measured using mass spectrometry. Tau concentration ratios for each proteoform were calculated to normalize for inter-individual differences. Receiver operating characteristic (ROC) curve analysis was performed for each biomarker against amyloid positivity, defined by > 20 Centiloids. Mixture of experts analysis assessed the value of including tau concentration ratios into the existing predictive algorithm for amyloid positron emission tomography status.<h4>Results</h4>The area under the receiver operating curve (AUC) was 0.87 for Aβ42/Aβ40, 0.74 for phosphorylated variant p-tau181 ratio (p-tau181/np-tau181), and 0.92 for phosphorylated variant p-tau217 ratio (p-tau217/np-tau217). The Plasma Predicted Centiloid (PPC), a predictive model including p-tau217/np-tau217, Aβ42/Aβ40, age, and apolipoprotein E improved AUC to 0.95.<h4>Discussion</h4>Including plasma p-tau217/np-tau217 along with Aβ42/Aβ40 in predictive algorithms may streamline screening preclinical individuals into anti-amyloid clinical trials.<h4>Clinicaltrials</h4>gov Identifier: NCT04468659 HIGHLIGHTS: The addition of plasma phosphorylated variant p-tau217 ratio (p-tau217/np-tau217) significantly improved plasma biomarker algorithms for identifying preclinical amyloid positron emission tomography positivity. Prediction performance at higher NAV Centiloid levels was improved with p-tau217/np-tau217. All models generated for this study are incorporated into the Plasma Predicted Centiloid (PPC) app for public use.","dates":{"release":"2024-01-01T00:00:00Z","publication":"2024 Feb","modification":"2025-08-24T03:09:13.82Z","creation":"2025-08-24T03:09:13.82Z"},"accession":"S-EPMC10916957","cross_references":{"pubmed":["37932961"],"doi":["10.1002/alz.13542"]}}