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

Alzheimers Dement. 2020 Feb;16(2):335-344. doi: 10.1016/j.jalz.2019.08.201. Epub 2020 Jan 4.


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 [18 F]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.

Keywords: Alzheimer's disease; Atrophy; Cognition; Dementia; Subtypes; Tau; Thickness.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Alzheimer Disease / classification*
  • Alzheimer Disease / diagnostic imaging
  • Alzheimer Disease / pathology*
  • Atrophy* / diagnostic imaging
  • Atrophy* / pathology
  • Carbolines
  • Cognitive Dysfunction / pathology
  • Female
  • Hippocampus / pathology
  • Humans
  • Image Processing, Computer-Assisted
  • Magnetic Resonance Imaging
  • Middle Aged
  • Positron-Emission Tomography*
  • White Matter / pathology
  • tau Proteins / metabolism*


  • Carbolines
  • tau Proteins
  • 7-(6-fluoropyridin-3-yl)-5H-pyrido(4,3-b)indole

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