Associations between quantitative [(18)F]flortaucipir tau PET and atrophy across the Alzheimer’s disease spectrum

BACKGROUND: Neuropathological studies have linked tau aggregates to neuronal loss. To describe the spatial distribution of neurofibrillary tangle pathology in post-mortem tissue, Braak staging has been used. The aim of this study was to examine in vivo associations between tau pathology, quantified with [(18)F]flortaucipir PET in regions corresponding to Braak stages, and atrophy across the Alzheimer’s disease (AD) spectrum. METHODS: We included 100 subjects, including 58 amyloid-β positive patients with mild cognitive impairment (MCI, n = 6) or AD dementia (n = 52) and 42 controls with subjective cognitive decline (36% amyloid-β positive). All subjects underwent a dynamic [(18)F]flortaucipir PET to generate non-displaceable binding potential (BP(ND)) maps. We extracted average [(18)F]flortaucipir BP(ND) entorhinal, Braak III–IV (limbic) and Braak V–VI (neocortical) regions of interest (ROIs). T1-weighted MRI was used to assess gray matter (GM) volumes. We performed linear regression analyses using [(18)F]flortaucipir BP(ND) ROIs as independent and GM density (ROI or voxelwise) as dependent variable. RESULTS: In MCI/AD subjects (age [mean ± SD] 65 ± 8 years, MMSE 23 ± 4), [(18)F]flortaucipir BP(ND) was higher than in controls (age 65 ± 8, MMSE 29 ± 1) across all ROIs (entorhinal 0.06 ± 0.21 vs 0.46 ± 0.25 p < 0.001, Braak III–IV 0.11 ± 0.10 vs 0.46 ± 0.26, p < 0.001, Braak V–VI 0.07 ± 0.07 vs 0.38 ± 0.29, p < 0.001). In MCI/AD, greater [(18)F]flortaucipir BP(ND) in entorhinal cortex was associated with lower GM density in medial temporal lobe (β − 0.40, p < 0.001). Greater [(18)F]flortaucipir BP(ND) in ROI Braak III–IV and Braak V–VI was associated with smaller GM density in lateral and inferior temporal, parietal, occipital, and frontal lobes (range standardized βs − 0.30 to − 0.55, p < 0.01), but not in medial temporal lobe (β − 0.22, p 0.07). [(18)F]Flortaucipir BP(ND) in ROI Braak I–II was not associated with GM density loss anywhere. When quantifying [(18)F]flortaucipir BP(ND) across brain lobes, we observed both local and distant associations with GM atrophy. In controls, there were no significant associations between [(18)F]flortaucipir BP(ND) and GM density (standardized βs ranging from − 0.24 to 0.02, all p > 0.05). CONCLUSIONS: In MCI/AD patients, [(18)F]flortaucipir binding in entorhinal, limbic, and neocortical regions was associated with cortical atrophy. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s13195-019-0510-3) contains supplementary material, which is available to authorized users.