Research ArticleAlzheimer’s Disease

Prospective longitudinal atrophy in Alzheimer’s disease correlates with the intensity and topography of baseline tau-PET

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Science Translational Medicine  01 Jan 2020:
Vol. 12, Issue 524, eaau5732
DOI: 10.1126/scitranslmed.aau5732

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Predictive PET

Understanding the dynamic of the two major hallmark of Alzheimer’s disease (AD), tau protein and β-amyloid, in the brain could allow better disease management. The use of positron emission tomography (PET) with specific radiotracers allows the visualization of tau-containing neurofibrillary tangles and β-amyloid plaques in vivo. Now, La Joie et al. performed longitudinal analysis of tau-PET and β-amyloid–PET in 32 patients with AD starting at early disease stage and correlated the signal with brain atrophy at later stages. In this cohort, tau-PET, but not β-amyloid–PET, signal could predict brain atrophy at later stages. Tau-PET might be useful for predicting disease progression and for designing and evaluating new therapies.

Abstract

β-Amyloid plaques and tau-containing neurofibrillary tangles are the two neuropathological hallmarks of Alzheimer’s disease (AD) and are thought to play crucial roles in a neurodegenerative cascade leading to dementia. Both lesions can now be visualized in vivo using positron emission tomography (PET) radiotracers, opening new opportunities to study disease mechanisms and improve patients’ diagnostic and prognostic evaluation. In a group of 32 patients at early symptomatic AD stages, we tested whether β-amyloid and tau-PET could predict subsequent brain atrophy measured using longitudinal magnetic resonance imaging acquired at the time of PET and 15 months later. Quantitative analyses showed that the global intensity of tau-PET, but not β-amyloid–PET, signal predicted the rate of subsequent atrophy, independent of baseline cortical thickness. Additional investigations demonstrated that the specific distribution of tau-PET signal was a strong indicator of the topography of future atrophy at the single patient level and that the relationship between baseline tau-PET and subsequent atrophy was particularly strong in younger patients. These data support disease models in which tau pathology is a major driver of local neurodegeneration and highlight the relevance of tau-PET as a precision medicine tool to help predict individual patient’s progression and design future clinical trials.

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