{"doi":"10.1002/alz.13542","title":"Plasma Aβ42/Aβ40 and phospho‐tau217 concentration ratios increase the accuracy of amyloid PET classification in preclinical Alzheimer's disease","abstract":"INTRODUCTION: Incorporating blood-based Alzheimer's disease biomarkers such as tau and amyloid beta (Aβ) into screening algorithms may improve screening efficiency. METHODS: 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. RESULTS: 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. DISCUSSION: Including plasma p-tau217/np-tau217 along with Aβ42/Aβ40 in predictive algorithms may streamline screening preclinical individuals into anti-amyloid clinical trials. CLINICALTRIALS: 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","year":2023,"id":315587,"datarank":3.358383703147971,"base_score":5.0106352940962555,"endowment":5.0106352940962555,"self_citation_contribution":0.7515952941144385,"citation_network_contribution":2.6067884090335323,"self_endowment_contribution":0.7515952941144385,"citer_contribution":2.6067884090335323,"corpus_percentile":null,"corpus_rank":null,"citation_count":149,"citer_count":100,"citers_with_citation_signal":84,"citers_with_endowment":84,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9265,"is_data_producer":true,"deposit_databanks":{"ClinicalTrials.gov":["NCT04468659"]},"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2023-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":363438,"name":"Oliver Langford","orcid":"0009-0006-8951-1326","position":1,"is_corresponding":false},{"id":226625,"name":"Rema Raman","orcid":"0000-0002-4096-6390","position":2,"is_corresponding":false},{"id":51716,"name":"Michael Donohue","orcid":"0000-0001-6026-2238","position":3,"is_corresponding":false},{"id":948771,"name":"Sara Abdel‐Latif","orcid":null,"position":4,"is_corresponding":false},{"id":98175,"name":"Matthew R. 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