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

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


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.


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 [18 F]flortaucipir (tau) positron emission tomography, white matter hyperintensity burden, and rate of global cognitive decline.


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.


Our data suggest that structural MRI can be used to identify biologically and clinically meaningful subtypes of AD.

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