Abstract
INTRODUCTION
Cerebrospinal fluid (CSF) tau phosphorylation at multiple sites is associated with cortical amyloid and other pathologic changes in Alzheimer’s disease. These relationships can be non-linear. We used an artificial neural network to assess the ability of 10 different CSF tau phosphorylation sites to predict continuous amyloid positron emission tomography (PET) values.
METHODS
CSF tau phosphorylation occupancies at 10 sites (including pT181/T181, pT217/T217, pT231/T231 and pT205/T205) were measured by mass spectrometry in 346 individuals (57 cognitively impaired, 289 cognitively unimpaired). We generated synthetic amyloid PET scans using biomarkers and evaluated their performance.
RESULTS
Concentration of CSF pT217/T217 had low predictive error (average error: 13%), but also a low predictive range (ceiling 63 Centiloids). CSF pT231/T231 has slightly higher error (average error: 19%) but predicted through a greater range (87 Centiloids).
DISCUSSION
Tradeoffs exist in biomarker selection. Some phosphorylation sites offer greater concordance with amyloid PET at lower levels, while others perform better over a greater range.
Highlights
Novel pTau isoforms can predict cortical amyloid burden.
pT217/T217 accurately predicts cortical amyloid burden in low-amyloid individuals.
Traditional CSF biomarkers correspond with higher levels of amyloid.
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This post is Copyright: Julie K. Wisch,
Brian A. Gordon,
Nicolas R. Barthélemy,
Kanta Horie,
Rachel L. Henson,
Yingxin He,
Shaney Flores,
Tammie L. S. Benzinger,
John C. Morris,
Randall J. Bateman,
Beau M. Ances,
Suzanne E. Schindler | July 23, 2024