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

• Published in: Alzheimer's & dementia Vol. 14; no. 7; pp. 913 - 924
• Main Authors: Mattsson, Niklas, Groot, Colin, Jansen, Willemijn J., Landau, Susan M., Villemagne, Victor L., Engelborghs, Sebastiaan, Mintun, Mark M., Lleo, Alberto, Molinuevo, José Luis, Jagust, William J., Frisoni, Giovanni B., Ivanoiu, Adrian, Chételat, Gaël, Resende de Oliveira, Catarina, Rodrigue, Karen M., Kornhuber, Johannes, Wallin, Anders, Klimkowicz-Mrowiec, Aleksandra, Kandimalla, Ramesh, Popp, Julius, Aalten, Pauline P., Aarsland, Dag, Alcolea, Daniel, Almdahl, Ina S., Baldeiras, Inês, van Buchem, Mark A., Cavedo, Enrica, Chen, Kewei, Cohen, Ann D., Förster, Stefan, Fortea, Juan, Frederiksen, Kristian S., Freund-Levi, Yvonne, Gill, Kiran Dip, Gkatzima, Olymbia, Grimmer, Timo, Hampel, Harald, Herukka, Sanna-Kaisa, Johannsen, Peter, van Laere, Koen, de Leon, Mony J., Maier, Wolfgang, Marcusson, Jan, Meulenbroek, Olga, Møllergård, Hanne M., Morris, John C., Mroczko, Barbara, Nordlund, Arto, Prabhakar, Sudesh, Peters, Oliver, Rami, Lorena, Rodríguez-Rodríguez, Eloy, Roe, Catherine M., Rüther, Eckart, Santana, Isabel, Schröder, Johannes, Seo, Sang W., Soininen, Hilkka, Spiru, Luiza, Stomrud, Erik, Struyfs, Hanne, Teunissen, Charlotte E., Verhey, Frans R.J., Vos, Stephanie J.B., van Waalwijk van Doorn, Linda J.C., Waldemar, Gunhild, Wallin, Åsa K., Wiltfang, Jens, Vandenberghe, Rik, Brooks, David J., Fladby, Tormod, Rowe, Christopher C., Drzezga, Alexander, Verbeek, Marcel M., Sarazin, Marie, Wolk, David A., Fleisher, Adam S., Klunk, William E., Na, Duk L., Sánchez-Juan, Pascual, Lee, Dong Young, Nordberg, Agneta, Tsolaki, Magda, Camus, Vincent, Rinne, Juha O., Fagan, Anne M., Zetterberg, Henrik, Blennow, Kaj, Rabinovici, Gil D., Hansson, Oskar, van Berckel, Bart N.M., van der Flier, Wiesje M., Scheltens, Philip, Visser, Pieter Jelle, Ossenkoppele, Rik
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.07.2018
• Subjects: Age; Alzheimer's disease; Amyloid; APOE; Clinical Medicine; CSF; Education; Geographical location; Klinisk medicin; Medical and Health Sciences; Medicin och hälsovetenskap; Mild cognitive impairment; Neurologi; Neurology; Neurosciences; Neurovetenskaper; PET; Prevalence; Sex; Subjective cognitive decline; Subjective cognitive decline; Prevalence; Mild cognitive impairment; Education; CSF; Sex; Geographical location; Amyloid; APOE; Alzheimer's disease; PET; Age
• ISSN: 1552-5260; 1552-5279; 1552-5279
• DOI: 10.1016/j.jalz.2018.02.009

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. 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. 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. 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. •The APOE ε4 prevalence in Alzheimer's disease has previously been underestimated.•The APOE ε4 prevalence decreases with age in early disease stages but not in dementia.•The prevalence of APOE ɛ4 is highest in Northern Europe.•Education and sex did not affect the prevalence of APOE ɛ4.