Tau Subtypes of Alzheimer's Disease Determined in vivo Using Flortaucipir PET Imaging

Arnaud Charil, Sergey Shcherbinin, Sudeepti Southekal, Michael D. Devous, Mark Mintun, Melissa E. Murray, Bradley B. Miller, Adam J. Schwarz

Research output: Contribution to journalArticle

Abstract

At autopsy, individuals with Alzheimer's disease (AD) exhibit heterogeneity in the distribution of neurofibrillary tangles in neocortical and hippocampal regions. Subtypes of AD, defined using an algorithm based on the relative number of tangle counts in these regions, have been proposed - hippocampal sparing (relative sparing of the hippocampus but high cortical load), limbic predominant (high hippocampal load but lower load in association cortices), and typical (balanced neurofibrillary tangles counts in the hippocampus and association cortices) AD - and shown to be associated with distinct antemortem clinical phenotypes. The ability to distinguish these AD subtypes from the more typical tau signature in vivo could have important implications for clinical research. Flortaucipir positron emission tomography (PET) images acquired from 45 amyloid-positive participants, defined clinically as mild cognitive impairment or AD, aged 50-92 years, 56% female, and estimated to be Braak V-VI based on their PET pattern of tau pathology, were studied. By translating the neuropathologic algorithm to flortaucipir PET scans, patterns of tau pathology consistent with autopsy findings, and with a similar prevalence, were identified in vivo. 6/45 (13%) participants were identified as hippocampal sparing and 6/45 (13%) as limbic predominant AD subtypes. Hippocampal sparing participants were significantly younger than those assigned to the other two subtypes. Worse performance on delayed recall was associated with increased hippocampal tau signal, and worse performance on the trail making test B-A was associated with lower values of the hippocampus to cortex ratio. Prospective studies can further validate the flortaucipir SUVR cut-points and the phenotype of the corresponding AD subtypes.

Original languageEnglish (US)
Pages (from-to)1037-1048
Number of pages12
JournalJournal of Alzheimer's Disease
Volume71
Issue number3
DOIs
StatePublished - Jan 1 2019

Keywords

  • Hippocampal sparing
  • limbic predominant
  • subtype
  • tau

ASJC Scopus subject areas

  • Neuroscience(all)
  • Clinical Psychology
  • Geriatrics and Gerontology
  • Psychiatry and Mental health

Fingerprint Dive into the research topics of 'Tau Subtypes of Alzheimer's Disease Determined in vivo Using Flortaucipir PET Imaging'. Together they form a unique fingerprint.

  • Cite this

    Charil, A., Shcherbinin, S., Southekal, S., Devous, M. D., Mintun, M., Murray, M. E., Miller, B. B., & Schwarz, A. J. (2019). Tau Subtypes of Alzheimer's Disease Determined in vivo Using Flortaucipir PET Imaging. Journal of Alzheimer's Disease, 71(3), 1037-1048. https://doi.org/10.3233/JAD-190264