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Clinical utility of plasma Aβ42/40 ratio by LC-MS/MS in Alzheimer's disease assessment
Darren M Weber1, Steven W Taylor1, Robert J Lagier1
1Quest Diagnostics Nichols Institute, San Juan Capistrano, CA, United States.
Introduction:
Plasma Aβ42/40 ratio can help predict amyloid PET status, but its clinical utility in Alzheimer's disease (AD) assessment is unclear.
Methods:
Aβ42/40 ratio was measured by LC-MS/MS for 250 specimens with associated amyloid PET imaging, diagnosis, and demographic data, and for 6,192 consecutive clinical specimens submitted for Aβ42/40 testing.
Results:
High diagnostic sensitivity and negative predictive value (NPV) for Aβ-PET positivity were observed, consistent with the clinical performance of other plasma LC-MS/MS assays, but with greater separation between Aβ42/40 values for individuals with positive vs. negative Aβ-PET results. Assuming a moderate prevalence of Aβ-PET positivity, a cutpoint was identified with 99% NPV, which could help predict that AD is likely not the cause of patients' cognitive impairment and help reduce PET evaluation by about 40%.
Conclusion:
High-throughput plasma Aβ42/40 LC-MS/MS assays can help identify patients with low likelihood of AD pathology, which can reduce PET evaluations, allowing for cost savings.
Insights
Plasma amyloid-beta 42/40 ratio (Aβ42/40) shows promise in predicting amyloid PET status for Alzheimer's disease (AD). This biomarker test can help identify patients unlikely to have AD pathology, potentially reducing costly PET scans.
Area of Science:
- Biochemistry
- Neurology
- Medical Diagnostics
Background:
- The plasma amyloid-beta 42/40 ratio (Aβ42/40) is a potential biomarker for predicting amyloid Positron Emission Tomography (PET) status.
- Its clinical utility in the assessment of Alzheimer's disease (AD) requires further clarification.
Purpose of the Study:
- To evaluate the diagnostic performance of plasma Aβ42/40 ratio using liquid chromatography-tandem mass spectrometry (LC-MS/MS).
- To determine the clinical utility of plasma Aβ42/40 in predicting amyloid PET positivity and aiding in Alzheimer's disease assessment.
Main Methods:
- Aβ42/40 ratio was measured using LC-MS/MS in 250 specimens with available amyloid PET imaging and diagnostic data.
- The assay was also performed on 6,192 clinical specimens submitted for Aβ42/40 testing.
Main Results:
- The plasma Aβ42/40 assay demonstrated high diagnostic sensitivity and negative predictive value (NPV) for Aβ-PET positivity.
- A specific cutpoint achieved 99% NPV, indicating a low likelihood of AD pathology.
- This approach could potentially reduce PET evaluations by approximately 40%.
Conclusions:
- High-throughput plasma Aβ42/40 LC-MS/MS assays are effective in identifying patients with a low probability of AD pathology.
- These assays can aid in reducing the need for PET evaluations, leading to significant cost savings.
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