Correlation and Interchangeability of Amyloid, Tau, and Glucose Metabolism PET in Mild Cognitive Impairment and Alzheimer: A Review

Positron emission tomography (PET) allows for minimally invasive in vivo localization of amyloid and tau deposition, and visualization of glucose metabolism using amyloid PET, tau PET, and FDG PET. Clinically, these scans are used to determine A, T, and N (amyloid-β plaques, tau tangles, and neurodegeneration) status in Alzheimer's disease. In light of the recent anti-amyloid therapies, determination of the A, and the associated T and N status is increasingly important. This review explores the potential of a single PET scan to define multiple biomarkers. A literature search using the PubMed database and an additional citation search using Google Scholar identified 76 relevant publications up to 30 July 2025. Original work reporting amyloid, tau or FDG PET to determine two or more ATN-related biomarkers were included. Non-English, animal, and non-dementia related studies were excluded. For each study, quantitative outcomes such as correlations and ROC AUC scores were extracted and compared. Early phase amyloid and tau PET (<i>n</i> = 58) were consistently found to be good indicators of N status with a median (IQR) correlation of 0.82 (0.76-0.86). Limited research (<i>n</i> = 7) was performed for amyloid or tau PET to infer both A and T status, with tau-based studies having slightly higher ROC AUC scores (0.88-0.99) than amyloid-based studies (0.84-0.9). Initial results are promising (median ROC AUC scores of 0.88 (0.81-0.96)) but need to be validated. FDG PET was found to be less accurate for A or T status (<i>n</i> = 12) prediction (median ROC AUC scores of 0.83 (0.80-0.87)). Among the modalities, tau PET seems to be the most promising candidate for a single tracer approach to predict all three biomarkers.