APOE ε4 influences medial temporal atrophy and tau deposition in atypical Alzheimer's disease

Neha Atulkumar Singh, Nirubol Tosakulwong, Jonathan Graff-Radford, Mary M. Machulda, Nha Trang Thu Pham, Irene Sintini, Stephen D. Weigand, Christopher G. Schwarz, Matthew L. Senjem, Minerva M. Carrasquillo, Nilufer Ertekin-Taner, Clifford R. Jack, Val J. Lowe, Keith A. Josephs, Jennifer L. Whitwell

Research output: Contribution to journalArticlepeer-review


Introduction: Apolipoprotein E (APOE) ε4 is an important genetic risk factor for typical Alzheimer's disease (AD), influencing brain volume and tau burden. Little is known about its influence in atypical presentations of AD. Methods: An atypical AD cohort of 140 patients diagnosed with either posterior cortical atrophy or logopenic progressive aphasia underwent magnetic resonance imaging and positron emission tomography. Linear mixed effects models were fit to assess the influence of APOE ε4 on cross-sectional and longitudinal regional metrics. Results: At baseline, APOE ε4 carriers had smaller hippocampal and amygdala volumes and greater tau standardized uptake volume ratio in the hippocampus and entorhinal cortex compared to non-carriers while longitudinally, APOE ε4 non-carriers showed faster rates of atrophy and tau accumulation in the entorhinal cortex, with faster tau accumulation in the hippocampus. Discussion: APOE ε4 influences patterns of neurodegeneration and tau deposition and was associated with more medial temporal involvement, although there is evidence that non-carriers may be catching up over time.

Original languageEnglish (US)
Pages (from-to)784-796
Number of pages13
JournalAlzheimer's and Dementia
Issue number3
StatePublished - Mar 2023


  • apolipoprotein ε4
  • atypical Alzheimer's disease
  • logopenic progressive aphasia
  • magnetic resonance imaging
  • posterior cortical atrophy
  • tau positron emission tomography

ASJC Scopus subject areas

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


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