Prevalence of the apolipoprotein E ε4 allele in amyloid β positive subjects across the spectrum of Alzheimer's disease

Niklas Mattsson, Colin Groot, Willemijn J. Jansen, Susan M. Landau, Victor L. Villemagne, Sebastiaan Engelborghs, Mark M. Mintun, Alberto Lleo, José Luis Molinuevo, William J. Jagust, Giovanni B. Frisoni, Adrian Ivanoiu, Gaël Chételat, Catarina Resende de Oliveira, Karen M. Rodrigue, Johannes Kornhuber, Anders Wallin, Aleksandra Klimkowicz-Mrowiec, Ramesh Kandimalla, Julius PoppPauline P. Aalten, Dag Aarsland, Daniel Alcolea, Ina S. Almdahl, Inês Baldeiras, Mark A. van Buchem, Enrica Cavedo, Kewei Chen, Ann D. Cohen, Stefan Förster, Juan Fortea, Kristian S. Frederiksen, Yvonne Freund-Levi, Kiran Dip Gill, Olymbia Gkatzima, Timo Grimmer, Harald Hampel, Sanna Kaisa Herukka, Peter Johannsen, Koen van Laere, Mony J. de Leon, Wolfgang Maier, Jan Marcusson, Olga Meulenbroek, Hanne M. Møllergård, John C. Morris, Barbara Mroczko, Arto Nordlund, Sudesh Prabhakar, Oliver Peters, Lorena Rami, Eloy Rodríguez-Rodríguez, Catherine M. Roe, Eckart Rüther, Isabel Santana, Johannes Schröder, Sang W. Seo, Hilkka Soininen, Luiza Spiru, Erik Stomrud, Hanne Struyfs, Charlotte E. Teunissen, Frans R.J. Verhey, Stephanie J.B. Vos, Linda J.C. van Waalwijk van Doorn, Gunhild Waldemar, Åsa K. Wallin, Jens Wiltfang, Rik Vandenberghe, David J. Brooks, Tormod Fladby, Christopher C. Rowe, Alexander Drzezga, Marcel M. Verbeek, Marie Sarazin, David A. Wolk, Adam S. Fleisher, William E. Klunk, Duk L. Na, Pascual Sánchez-Juan, Dong Young Lee, Agneta Nordberg, Magda Tsolaki, Vincent Camus, Juha O. Rinne, Anne M. Fagan, Henrik Zetterberg, Kaj Blennow, Gil D. Rabinovici, Oskar Hansson, Bart N.M. van Berckel, Wiesje M. van der Flier, Philip Scheltens, Pieter Jelle Visser, Rik Ossenkoppele

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31 Scopus citations

Abstract

Introduction: Apolipoprotein E (APOE) ε4 is the major genetic risk factor for Alzheimer's disease (AD), but its prevalence is unclear because earlier studies did not require biomarker evidence of amyloid β (Aβ) pathology. Methods: We included 3451 Aβ+ subjects (853 AD-type dementia, 1810 mild cognitive impairment, and 788 cognitively normal). Generalized estimating equation models were used to assess APOE ε4 prevalence in relation to age, sex, education, and geographical location. Results: The APOE ε4 prevalence was 66% in AD-type dementia, 64% in mild cognitive impairment, and 51% in cognitively normal, and it decreased with advancing age in Aβ+ cognitively normal and Aβ+ mild cognitive impairment (P <.05) but not in Aβ+ AD dementia (P =.66). The prevalence was highest in Northern Europe but did not vary by sex or education. Discussion: The APOE ε4 prevalence in AD was higher than that in previous studies, which did not require presence of Aβ pathology. Furthermore, our results highlight disease heterogeneity related to age and geographical location.

Original languageEnglish
Pages (from-to)913-924
Number of pages12
JournalAlzheimer's and Dementia
Volume14
Issue number7
DOIs
StatePublished - Jul 2018

Keywords

  • APOE
  • Age
  • Alzheimer's disease
  • Amyloid
  • CSF
  • Education
  • Geographical location
  • Mild cognitive impairment
  • PET
  • Prevalence
  • Sex
  • Subjective cognitive decline

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