Distinct tau PET patterns in atrophy-defined subtypes of Alzheimer's disease

Rik Ossenkoppele, Chul Hyoung Lyoo, Carole H. Sudre, Danielle van Westen, Hanna Cho, Young Hoon Ryu, Jae Yong Choi, Ruben Smith, Olof Strandberg, Sebastian Palmqvist, Erik Westman, Richard Tsai, Joel Kramer, Adam L. Boxer, Maria L. Gorno-Tempini, Renaud La Joie, Bruce L. Miller, Gil D. Rabinovici, Oskar Hansson

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Abstract

Introduction: Differential patterns of brain atrophy on structural magnetic resonance imaging (MRI) revealed four reproducible subtypes of Alzheimer's disease (AD): (1) “typical”, (2) “limbic-predominant”, (3) “hippocampal-sparing”, and (4) “mild atrophy”. We examined the neurobiological characteristics and clinical progression of these atrophy-defined subtypes. Methods: The four subtypes were replicated using a clustering method on MRI data in 260 amyloid-β–positive patients with mild cognitive impairment or AD dementia, and we subsequently tested whether the subtypes differed on [18F]flortaucipir (tau) positron emission tomography, white matter hyperintensity burden, and rate of global cognitive decline. Results: Voxel-wise and region-of-interest analyses revealed the greatest neocortical tau load in hippocampal-sparing (frontoparietal-predominant) and typical (temporal-predominant) patients, while limbic-predominant patients showed particularly high entorhinal tau. Typical patients with AD had the most pronounced white matter hyperintensity load, and hippocampal-sparing patients showed the most rapid global cognitive decline. Discussion: Our data suggest that structural MRI can be used to identify biologically and clinically meaningful subtypes of AD.

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All Science Journal Classification (ASJC) codes

  • Epidemiology
  • Health Policy
  • Developmental Neuroscience
  • Clinical Neurology
  • Geriatrics and Gerontology
  • Psychiatry and Mental health
  • Cellular and Molecular Neuroscience

Cite this

Ossenkoppele, R., Lyoo, C. H., Sudre, C. H., van Westen, D., Cho, H., Ryu, Y. H., Choi, J. Y., Smith, R., Strandberg, O., Palmqvist, S., Westman, E., Tsai, R., Kramer, J., Boxer, A. L., Gorno-Tempini, M. L., La Joie, R., Miller, B. L., Rabinovici, G. D., & Hansson, O. (Accepted/In press). Distinct tau PET patterns in atrophy-defined subtypes of Alzheimer's disease. Alzheimer's and Dementia. https://doi.org/10.1016/j.jalz.2019.08.201