Association between total amyloid beta plasma levels (AB 42/40, AB42 and AB40) and amyloid burden as measured by AB-PET SUVr levels
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Abstract
OBJECTIVE: Currently, an official diagnosis of Alzheimer’s disease (AD) involves expensive brain scans. Thus, these diagnostic tools are inefficient for targeting large populations and individuals with limited resources. The overarching objective of this thesis project was to explore the association between plasma total Aβ levels (Aβ 42/40, Aβ42 and Aβ40) and amyloid burden as measured by Aβ-PET SUVr levels in a subset of participants screened in the A4 trial. Ultimately, this project aimed to uncover if blood Aβ biomarkers yielded comparable diagnostic results to PET scans. The first goal was to utilize appropriate statistics to determine whether there is a correlation between blood-based Aβ biomarkers and PET SUVr levels. The second goal was to analyze the relationship between blood-based amyloid beta biomarkers and PET positive and negative groups. METHODS: The first statistical analysis involved a Spearman Correlation test, which aimed to explore the relationship between Aβ blood-plasma levels and PET SUVr levels. Notably, this test can determine the strength of the correlation between blood-based Aβ biomarkers and PET SUVr levels. The second statistical test was a logistic regression model that aimed to build a prediction model and assess its potential clinical utility for AD screening. Before conducting the test, the SUVr quantities were assigned into a binary positive or negative scale based on an individual’s official AD diagnosis. RESULTS: Using the Spearman Correlation, I found that the Aβ40 was not correlated with PET SUVr levels since the coefficient value (ρ) = 0.042. Conversely, the Aβ42 showed a weak negative correlation with a ρ value of -0.14. Additionally, the Aβ 42/40 ratio exhibited the strongest correlation between all three scatterplots with a ρ value of -0.29. Individuals who were APOE e4 carriers consistently exhibited elevated PET SUVr levels compared to APOE e4 non-carriers when controlling for Aβ 42/40 levels and age. Regarding the logistic regression model, the results display the logistical regression model outperformed the Aβ 42/40 biomarker when comparing sensitivity for each specificity point. However, this attribution is based on the selection of the Youden index point. Based on the Area Under the Curve (AUC), the Aβ 42/40 has an AUC of 0.67 which provides moderate accuracy. Moreover, the logistic regression model which incorporates Aβ 42/40, age, and APOE e4 status has a significantly better AUC of 0.747. CONCLUSION: In conclusion, Aβ 42 and Aβ 42/40 exhibited weak correlations with PET SUVr levels with the strongest being Aβ 42/40 ratio. Additionally, APOE e4 carriers displayed elevated PET SUVr levels for all ranges of Aβ 42/40 and age with a 95% confidence interval. Furthermore, the logistical regression model that accounted for Aβ 42/40 ratio, APOE e4 gene, and age resulted in a higher AUC compared to solely the Aβ 42/40 ratio. Ultimately, the journey toward developing effective diagnostic tools for Alzheimer's disease may require refinement of multiple blood-based biomarkers to achieve optimal predictive power and clinical utility.
Description
2024
License
Attribution-NonCommercial-NoDerivatives 4.0 International