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Related Experiment Video

Updated: Jun 20, 2025

Hybrid PET/MRI Imaging of Alzheimer's Disease Based on 18F-AV-1451
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Predicting continuous amyloid PET values with CSF tau phosphorylation occupancies.

Julie K Wisch1, Brian A Gordon2,3, Nicolas R Barthélemy1,4

  • 1Department of Neurology, Washington University in St. Louis, St. Louis, Missouri, USA.

Alzheimer'S & Dementia : the Journal of the Alzheimer'S Association
|July 23, 2024
PubMed
Summary

Cerebrospinal fluid tau biomarkers show varying accuracy in predicting Alzheimer's disease amyloid PET. Novel tau isoforms offer better prediction across a wider range of amyloid levels.

Keywords:
CSF tau occupancyPETbiomarker concordancemachine learningnovel biomarkers

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Area of Science:

  • Neuroscience
  • Biochemistry

Background:

  • Cerebrospinal fluid (CSF) tau phosphorylation correlates with Alzheimer's disease (AD) pathology, including cortical amyloid.
  • Relationships between CSF tau phosphorylation and amyloid burden can be complex and non-linear.

Purpose of the Study:

  • To evaluate the predictive performance of 10 CSF tau phosphorylation sites for continuous amyloid positron emission tomography (PET) values using artificial neural networks.
  • To identify optimal CSF tau biomarkers for assessing amyloid burden in Alzheimer's disease.

Main Methods:

  • Mass spectrometry was used to measure CSF tau phosphorylation occupancies at 10 sites in 346 individuals.
  • Artificial neural networks were employed to predict synthetic amyloid PET scans generated from biomarker data.

Main Results:

  • CSF pT217/T217 demonstrated low predictive error (13%) but a limited predictive range (63 Centiloids).
  • CSF pT231/T231 showed higher error (19%) but a broader predictive range (87 Centiloids).

Conclusions:

  • A trade-off exists between CSF tau biomarker sensitivity at lower amyloid levels and range of prediction.
  • Novel tau phosphorylation isoforms can predict cortical amyloid burden, with pT217/T217 being accurate for low-amyloid individuals, while traditional biomarkers correlate with higher amyloid levels.