Abstract
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Objectives: Longitudinal tau PET may prove useful for clinical trials, through its ability to detect patterns and rates of in vivo tau accumulation in ageing and Alzheimer’s disease (AD). Clinical trials are increasingly targeting the preclinical phase of AD. Flortaucipir studies estimate a 3% annual increase in global cortical tau SUVR in Aβ+ve cognitively impaired (CI) cohorts, whereas either no change, or low rates of increase (0.5%), have been demonstrated in Aβ+ve cognitively unimpaired (CU) cohorts. F-18 MK6240 is a novel tau tracer with high target to background binding. We aimed to evaluate regional rates of 18F-MK6240 accumulation in ageing and throughout the AD continuum.
Methods: We performed PET acquisition 90-100 minutes post injection of 185MBq (±10%) 18F-MK6240 at baseline and 12 months in 67 Aβ-ve CU, 20 Aβ+ve CU and 19 Aβ+ve CI participants. SUVR for the entorhinal cortex, amygdala, hippocampus, parahippocampus and composite ROI (Me, mesial temporal and Te, temporoparietal cortices) were generated using the cerebellar cortex as the reference region.
Results: Age did not significantly differ between the groups (mean age 74 ± 4.4 Aβ-ve CU, 76.2 ± 5.7 Aβ+ve CU, 72.5 ± 6.4 Aβ+ve CI). Aβ+ve participants had higher baseline SUVR and higher annual percentage increase in SUVR relative to Aβ-ve participants in all regions examined (Table 1) (Figure 1A-B). Regional rates of increase varied between Aβ+ve groups, with larger increases seen in Te vs Me regions for the Aβ+ve CI group (4.3% vs 1.9%), while the inverse was seen for the Aβ+ve CU group (0.7% vs 1.6%). Annual rates of increase discriminated between Aβ+ve CU and Aβ-ve CU in the amygdala (2.9% vs 1.8%) and entorhinal cortex (1.9% vs 0.7%).
Conclusions: Longitudinal tau imaging using 18F-MK6240 discriminates between ageing (Aβ-ve CU) and the AD continuum (Aβ+ve CU and Aβ+ve CI). Rates of accumulation were highest in the mesial temporal region in preclinical AD (Aβ+ve CU) and the temporoparietal cortex in Aβ+ve CI individuals. Direct comparison to flortaucipir studies is limited by differences in ROI examined. The amygdala and entorhinal cortex may be early regions to discriminate tau accumulation between Aβ-ve CU and Aβ+ve CU groups. However, as the variance is large, the precision of these estimates may be refined with a larger sample size. Recruitment is ongoing. Acknowledgements: The data used in the preparation of this article was obtained from the Australian Imaging Biomarkers and Lifestyle flagship study of aging (AIBL), funded by the Commonwealth Scientific and Industrial Research Organization (CSIRO), National Health and Medical Research Council of Australia (NHMRC), and participating institutions. AIBL researchers are listed at www.aibl.csiro.au. NK was supported by a cofunded PhD scholarship from Australian Rotary Health/ Bartolina Peluso.