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Cardiac biomarkers are enzymes, proteins, and hormones released into the blood when cardiac cells are injured. They are powerful tools for triaging.
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Dried Blood Spot Collection of Health Biomarkers to Maximize Participation in Population Studies
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Biomarkers.

Yishu Chao1, Trevor A Chadwick1, Karly Cody2

  • 1University of California, Berkeley, Berkeley, CA, USA.

Alzheimer'S & Dementia : the Journal of the Alzheimer'S Association
|December 25, 2025
PubMed
Summary
This summary is machine-generated.

Off-target signal (OTS) in tau PET imaging, particularly with the PI2620 tracer, can lead to false positives in amyloid-negative individuals. This highlights the need to carefully assess OTS in quantitative tau PET analyses for accurate disease staging.

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Area of Science:

  • Neuroimaging
  • Molecular Imaging
  • Alzheimer's Disease Research

Background:

  • Quantitative tau Positron Emission Tomography (PET) imaging is crucial for staging neurodegenerative diseases.
  • Off-target signal (OTS) from tau PET ligands can potentially confound quantitative analyses.
  • Understanding the impact of OTS on disease staging is essential for accurate diagnosis and treatment monitoring.

Purpose of the Study:

  • To investigate the influence of off-target signal (OTS) associated with tau PET ligands on quantitative disease staging.
  • To determine if and how OTS affects tau positivity rates in different amyloid statuses.

Main Methods:

  • Utilized tau PET (MK6240, PI2620, FTP) and MRI scans from individuals over 55 years old.
  • Harmonized pipelines were used for scan processing, with tau PET scans normalized by the inferior cerebellum.
  • Off-target signal (OTS) regions of interest (ROIs) were defined and applied, and amyloid status was determined using global beta-amyloid (Ab) SUVRs.

Main Results:

  • Distinct OTS patterns were observed for each tracer: MK6240 showed meningeal binding, PI2620 exhibited skull, meningeal, and white matter OTS, and FTP had elevated signal in basal ganglia and white matter.
  • For PI2620, significant interaction effects between tau and amyloid status were found in all OTS ROIs, particularly in amyloid-negative (Ab-) individuals.
  • These interactions suggest that OTS may contribute to false positives in tau PET imaging, especially in the Ab- group.

Conclusions:

  • Elevated OTS was detected in the tau-positive, amyloid-negative (T+Ab-) group for the PI2620 tracer.
  • OTS may lead to false-positive tau positivity in cognitively unimpaired amyloid-negative subjects.
  • Further visual inspection of scans is recommended to quantify the rate of OTS-related false tau positivity.