Characterization of tau PET according to amyloid chronicity

Abstract

AbstractBackgroundThis work examined tau PET (MK‐6240 SUVR) relative to amyloid chronicity (duration of amyloid positivity (A+)) to better understand neurofibrillary tangle (NFT) spatial burden across the time course of Alzheimer’s disease (AD).MethodIndividuals (N=457, 68.3±7.1 years, 417 CU, 30 MCI, 10 dementia) from the Wisconsin Registry for Alzheimer’s Prevention and Wisconsin AD Research Center underwent amyloid and tau PET and neuropsychological assessment. Cortical 11C‐PiB DVR and sampled iterative local approximation was used to estimate A+ onset age and years of A+ duration at tau PET. Tau burden was quantified using 18F‐MK‐6240 SUVR (70‐90 min, inferior cerebellar GM reference region). MK‐6240 SUVR was assessed for relationships with A+ duration (continuous and grouped by decade) and clinical diagnosis as well as spatial patterns corresponding to Braak NFT stages. Regional and voxelwise analyses were performed.ResultMK‐6240 SUVR was positively associated with A+ duration in regions associated with Braak NFT stages I‐VI while age was not associated after accounting for A+ duration (Figure 1A). In the CU subset, the MK‐6240/A+ duration association was spatially restricted to regions associated with NFT stages I‐IV(Figure 1B). Voxelwise MK‐6240 analyses revealed that with each decade of A+ duration, the spatial extent of measurable tau “spread”(ie .progressed) from regions associated with early to late Braak NFT stages (Figure 2A). Similar patterns were observed in the CU subset, but with lower SUVR and signal spatially restricted to the medial temporal lobe (MTL; Figure 2B). Regional analyses of MK‐6240 SUVR Z‐scores indicated significant stepwise increases across A+ duration groups (A‐ < A+ 0‐10 years < A+ 10‐20 years <A+ 20+ years; Figure 3A) and across clinical groups (CN A‐ < CN A+ < MCI A+ < AD A+; Figures 3B). Between group differences were largest in the entorhinal cortex and MTL Meta‐ROI for both A+ duration and clinical diagnosis groups (Figure 4A‐B).ConclusionResults suggest that entorhinal and MTL regions were most sensitive to early amyloid pathology and cognitive changes in AD. Applying the amyloid chronicity framework to tau PET data enables 'pseudo'spatiotemporal characterization of tau deposition patterns in the AD continuum. Longitudinal assessment of spatiotemporal tau deposition patterns is ongoing.