Objectives To explore whether regional tau binding measured at baseline is associated with the rapidity of Alzheimer’s disease (AD) progression over 2 years, as assessed by the decline in specified cognitive domains, and the progression of regional brain atrophy, in comparison with amyloid-positron emission tomography (PET), MRI and cerebrospinal fluid (CSF) biomarkers.
Methods Thirty-six patients with AD (positive CSF biomarkers and amyloid-PET) and 15 controls underwent a complete neuropsychological assessment, 3T brain MRI, [11C]-PiB and [18F]-flortaucipir PET imaging, and were monitored annually over 2 years, with a second brain MRI after 2 years. We used mixed effects models to explore the relations between tau-PET, amyloid-PET, CSF biomarkers and MRI at baseline and cognitive decline and the progression of brain atrophy over 2 years in patients with AD.
Results Baseline tau-PET was strongly associated with the subsequent cognitive decline in regions that are usually associated with each cognitive domain. No significant relationship was observed between the cognitive decline and initial amyloid load, regional cortical atrophy or CSF biomarkers. Baseline tau tracer binding in the superior temporal gyrus was associated with subsequent atrophy in an inferomedial temporal volume of interest, as was the voxelwise tau tracer binding with subsequent cortical atrophy in the superior temporal, parietal and frontal association cortices.
Conclusions These results suggest that tau tracer binding is predictive of cognitive decline in AD in domain-specific brain areas, which provides important insights into the interaction between tau burden and neurodegeneration, and is of the utmost importance to develop new prognostic markers that will help improve the design of therapeutic trials.
- Alzheimer's disease
Data availability statement
Data are available on reasonable request.
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Contributors JL, MS and MB designed the work; acquired, analysed and interpreted the data and drafted the manuscript. PO analysed and interpreted the data, revised the manuscript and approved its final version. MT analysed and interpreted the data, revised the manuscript and approved its final version. CT and IR were involved in data analysis, revised the manuscript and approved its final version. PG, FC and MM were involved in data acquisition, revised the manuscript and approved its final version. Authors responsible for the overall content as the guarantors: JL and MS
Funding This study was funded by French Ministry of Health grant (PHRC-2013-0919), CEA (no award/grant number), Fondation pour la recherche sur la maladie d’Alzheimer (no award/grant number), Institut de Recherches Internationales Servier (no award/grant number), France-Alzheimer (no award/grant number).
Competing interests None declared.
Provenance and peer review Not commissioned; externally peer reviewed.
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