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Cited by 157Dementia and Cognitive Impairment ResearchAlzheimer's disease research and treatmentsCerebrospinal fluid and hydrocephalus

Plasma Aβ42/Aβ40 and phospho‐tau217 concentration ratios increase the accuracy of amyloid PET classification in preclinical Alzheimer's disease

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Rissman, Robert A., Langford, Oliver, Raman, Rema, Donohue, Michael C., Abdel‐Latif, Sara, Meyer, Matthew R., Wente‐Roth, Traci, Kirmess, Kristopher M. +13 more·2024·Alzheimer's & Dementia
DOI 10.1002/alz.13542PMC PMC10916957
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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.

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Authors
Rissman, R. A., Langford, O., Raman, R., Donohue, M. C., Abdel‐Latif, S., Meyer, M. R., Wente‐Roth, T., Kirmess, K. M., Ngolab, J., Winston, C. N., Jimenez‐Maggiora, G., Rafii, M. S., Sachdev, P., West, T., Yarasheski, K. E., Braunstein, J. B., Irizarry, M., Johnson, K. A., Aisen, P. S., Sperling, R. A., & for the AHEAD 3‐45 Study team
Affiliations
  • University of Southern California (US)
  • C2N Diagnostics (United States) (US)
  • Eisai (United States) (US)
  • Brigham and Women's Hospital (US)
Corresponding author
Rissman, Robert A.
ORCID
Venue
Alzheimer's & Dementia
Publisher
Wiley
Published
2023-11-06
Volume
20
Issue
2
Pages
1214-1224
ISSN
  • 1552-5260 (ISSN-L)
  • 1552-5279
DOI
10.1002/alz.13542
PMC
PMC10916957
OpenAlex
W4388461419
Cited by
157
References
50
Citations by year
2026: 54 · 2025: 59 · 2024: 42 · 2023: 2
FWCI
31.97
Type
journal article
Language
en
Open access
Licence
Locations
  • Alzheimer s & Dementia (publishedVersion, cc-by-nc-nd)
  • PubMed Central (publishedVersion, cc-by-nc-nd)
  • PubMed (publishedVersion)
  • UNSWorks (University of New South Wales, Sydney, Australia) (submittedVersion, cc-by-nc-nd)
Funders
  • BrightFocus Foundation (R44 AG059489, GC-201711-2013978, CA2016636)
  • National Institutes of Health (CA2016636, AG054029, AG018440, AG073979, AG058533)
  • National Institute on Aging (R37AG018440, AG018440, R01AG018440, CA2016636, AG058533, AG073979, AG058252, R01AG053798, K99AG070390, R01AG061848, R01AG058252, R01AG054029, R44AG059489, RF1AG073979, R56AG058533, R01AG050595, R01AG073979, R01AG058533, U24AG057437, P30AG066530, U19AG078109)
  • National Institute of Neurological Disorders and Stroke (R25NS117367)
Topics
  • Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
  • Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Cerebrospinal fluid and hydrocephalus
Keywords
preclinical Alzheimer's disease, amyloid PET
MeSH terms
Alzheimer Disease, Amyloid, Humans, Peptide Fragments, Biomarkers, Amyloid beta-Peptides, tau Proteins, Positron-Emission Tomography

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