Sex and APOE ε4 carrier effects on atrophy, amyloid PET, and tau PET burden in early-onset Alzheimer's disease

Sára Nemes, Paige E. Logan, Mohit K. Manchella, Nidhi S. Mundada, Renaud La Joie, Angelina J. Polsinelli, Dustin B. Hammers, Robert A. Koeppe, Tatiana M. Foroud, Kelly N. Nudelman, Ani Eloyan, Leonardo Iaccarino, Valérie Dorsant-Ardón, Alexander Taurone, Maryanne Thangarajah, Jeffery L. Dage, Paul Aisen, Lea T. Grinberg, Clifford R. Jack, Joel KramerWalter A. Kukull, Melissa E. Murray, Malia Rumbaugh, David N. Soleimani-Meigooni, Arthur Toga, Alexandra Touroutoglou, Prashanthi Vemuri, Alireza Atri, Gregory S. Day, Ranjan Duara, Neill R. Graff-Radford, Lawrence S. Honig, David T. Jones, Joseph Masdeu, Mario F. Mendez, Erik Musiek, Chiadi U. Onyike, Meghan Riddle, Emily Rogalski, Stephen Salloway, Sharon J. Sha, Raymond S. Turner, Thomas S. Wingo, Kyle B. Womack, David A. Wolk, Gil D. Rabinovici, Maria C. Carrillo, Bradford C. Dickerson, Liana G. Apostolova

Research output: Contribution to journalArticlepeer-review

2 Scopus citations

Abstract

INTRODUCTION: We used sex and apolipoprotein E ε4 (APOE ε4) carrier status as predictors of pathologic burden in early-onset Alzheimer's disease (EOAD). METHODS: We included baseline data from 77 cognitively normal (CN), 230 EOAD, and 70 EO non-Alzheimer's disease (EOnonAD) participants from the Longitudinal Early-Onset Alzheimer's Disease Study (LEADS). We stratified each diagnostic group by males and females, then further subdivided each sex by APOE ε4 carrier status and compared imaging biomarkers in each stratification. Voxel-wise multiple linear regressions yielded statistical brain maps of gray matter density, amyloid, and tau PET burden. RESULTS: EOAD females had greater amyloid and tau PET burdens than males. EOAD female APOE ε4 non-carriers had greater amyloid PET burdens and greater gray matter atrophy than female ε4 carriers. EOnonAD female ε4 non-carriers also had greater gray matter atrophy than female ε4 carriers. DISCUSSION: The effects of sex and APOE ε4 must be considered when studying these populations. HIGHLIGHTS: Novel analysis examining the effects of biological sex and apolipoprotein E ε4 (APOE ε4) carrier status on neuroimaging biomarkers among early-onset Alzheimer's disease (EOAD), early-onset non-AD (EOnonAD), and cognitively normal (CN) participants. Female sex is associated with greater pathology burden in the EOAD cohort compared to male sex. The effect of APOE ε4 carrier status on pathology burden was the most impactful in females across all cohorts.

Original languageEnglish
Pages (from-to)S49-S63
JournalAlzheimer's and Dementia
Volume19
Issue numberS9
DOIs
StatePublished - Nov 2023

Keywords

  • APOE ε4
  • MRI
  • amyloid PET
  • early-onset Alzheimer's disease
  • early-onset non-Alzheimer's disease
  • genetics
  • imaging biomarkers
  • neuroimaging
  • sex differences
  • tau PET

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