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Specific associations between plasma biomarkers and postmortem amyloid plaque and tau tangle loads
Gemma Salvadó1, Rik Ossenkoppele1,2,3, Nicholas J Ashton4,5,6
1Clinical Memory Research Unit, Department of Clinical Sciences, Malmö, Lund University, Lund, Sweden.
EMBO Molecular Medicine
|March 13, 2023
Summary
Plasma biomarkers like p-tau217 and Aβ42/40 show promise for detecting Alzheimer's disease (AD) pathology. Combining these biomarkers offers the highest accuracy in predicting AD neuropathological changes and plaque load.
Area of Science:
- Neurology
- Biomarker Discovery
- Neurodegenerative Diseases
Background:
- Plasma biomarkers for Alzheimer's disease (AD) are emerging, but their direct correlation with neuropathology requires further investigation.
- Understanding the relationship between plasma biomarkers and in vivo brain pathology is crucial for accurate AD diagnosis and monitoring.
Purpose of the Study:
- To investigate and compare the independent associations between multiple plasma biomarkers (p-tau181, p-tau217, p-tau231, Aβ42/40, GFAP, NfL) and neuropathologic measures of amyloid plaques and tau tangles.
- To determine the optimal combination of plasma biomarkers for predicting Alzheimer's disease neuropathological change (ADNC).
Main Methods:
- Analysis of antemortem plasma samples and postmortem neuropathological examination from 105 participants in the Arizona Study of Aging and Neurodegenerative Disorders (AZSAND).
- Statistical correlation analyses were performed to assess associations between plasma biomarkers and neuropathologic measures of plaque and tangle loads.
- A predictive model combining p-tau217 and Aβ42/40 was evaluated for its accuracy in predicting ADNC and plaque/tangle loads.
Main Results:
- Plasma Aβ42/40 ratio and p-tau231 were associated with amyloid plaques, while GFAP was associated with tau tangles.
- Plasma p-tau217 and p-tau181 showed associations with both amyloid plaques and tau tangles.
- A combined model of p-tau217 and Aβ42/40 achieved the highest accuracy (AUC=0.89) for predicting ADNC and plaque load (R²=0.55). P-tau217 alone was optimal for predicting tangle load (R²=0.45).
Conclusions:
- Plasma p-tau217 and Aβ42/40 ratio are strongly associated with core Alzheimer's disease neuropathologic features.
- A combination of plasma p-tau217 and Aβ42/40 assays may serve as an optimal non-invasive tool for assessing Alzheimer's-related pathology in vivo.
- These findings support the potential of plasma biomarkers in improving the diagnosis and management of Alzheimer's disease.
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