F-APN-1607 Tau Positron Emission Tomography Imaging for Evaluating Disease Progression in Alzheimer's Disease.

Purpose: F-APN-1607 is a novel tau positron emission tomography (PET) tracer characterized with high binding affinity for 3- and 4-repeat tau deposits. The aim was to analyze the spatial distribution of F-APN-1607 PET imaging in Alzheimer's disease (AD) subjects with different stages and to investigate the relationship between the change of tau deposition and overall disease progression.

Methods: We retrospectively analyzed the F-APN-1607 PET imaging of 31 subjects with clinically and imaging defined as AD. According to the Mini-Mental State Examination (MMSE) score, patients were divided into three groups, namely, mild (≥21, = 7), moderate (10-20, = 16), and severe (≤9, = 8). PET imaging was segmented to 70 regions of interest (ROIs) and extracted the standard uptake value (SUV) of each ROI. SUV ratio (SUVR) was calculated from the ratio of SUV in different brain regions to the cerebellar cortex. The regions were defined as positive and negative with unsupervised cluster analysis according to SUVR. The SUVRs of each region were compared among groups with the one-way ANOVA or Kruskal-Wallis test. Furthermore, the correlations between MMSE score and regional SUVR were calculated with Pearson or Spearman correlation analysis.

Results: There were no significant differences among groups in gender (χ = 3.814, = 0.161), age of onset ( = 0.170), age ( = 0.109), and education level ( = 0.065). With the disease progression, the F-APN-1607 PET imaging showed the spread of tau deposition from the hippocampus, posterior cingulate gyrus (PCG), and lateral temporal cortex (LTC) to the parietal and occipital lobes, and finally to the frontal lobe. Between the mild and moderate groups, the main brain areas with significant differences in F-APN-1607 uptake were supplementary motor area (SMA), cuneus, precuneus, occipital lobule, paracentral lobule, right angular gyrus, and parietal, which could be used for early disease progression assessment ( < 0.05). There were significant differences in the frontal lobe, right temporal lobe, and fusiform gyrus between the moderate and severe groups, which might be suitable for the late-stage disease progression assessment ( < 0.05).

Conclusion: F-APN-1607 PET may serve as an effective imaging marker for visualizing the change pattern of tau protein deposition in AD patients, and its uptake level in certain brain regions is closely related to the severity of cognitive impairment. These indicate the potential of F-APN-1607 PET for the evaluation of the progression of AD.