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

Mattsson, Niklas LU ; Groot, Colin; Jansen, Willemijn J.; Landau, Susan M.; Villemagne, Victor L.; Engelborghs, Sebastiaan; Mintun, Mark M.; Lleo, Alberto; Molinuevo, José Luis and Jagust, William J., et al. (2018) In Alzheimer's and Dementia 14(7). p.913-924
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... (More)

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.

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keywords
Age, Alzheimer's disease, Amyloid, APOE, CSF, Education, Geographical location, Mild cognitive impairment, PET, Prevalence, Sex, Subjective cognitive decline
in
Alzheimer's and Dementia
volume
14
issue
7
pages
913 - 924
publisher
Elsevier
external identifiers
  • scopus:85045929153
ISSN
1552-5260
DOI
10.1016/j.jalz.2018.02.009
language
English
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yes
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50e72dbd-9a4a-4abf-ad00-0ae9efb2dd9e
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2018-05-07 12:17:54
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2019-01-09 16:31:31
@article{50e72dbd-9a4a-4abf-ad00-0ae9efb2dd9e,
  abstract     = {<p>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 &lt;.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.</p>},
  author       = {Mattsson, Niklas and Groot, Colin and Jansen, Willemijn J. and Landau, Susan M. and Villemagne, Victor L. and Engelborghs, Sebastiaan and Mintun, Mark M. and Lleo, Alberto and Molinuevo, José Luis and Jagust, William J. and Frisoni, Giovanni B. and Ivanoiu, Adrian and Chételat, Gaël and Resende de Oliveira, Catarina and Rodrigue, Karen M. and Kornhuber, Johannes and Wallin, Anders and Klimkowicz-Mrowiec, Aleksandra and Kandimella, Ramesh and Popp, Julius and Aalten, Pauline P. and Aarsland, Dag and Alcolea, Daniel and Almdahl, Ina S. and Baldeiras, Inês and van Buchem, Mark A. and Cavedo, Enrica and Chen, Kewei and Cohen, Ann D. and Förster, Stefan and Fortea, Juan and Frederiksen, Kristian S. and Freund-Levi, Yvonne and Gill, Kiran Dip and Gkatzima, Olymbia and Grimmer, Timo and Hampel, Harald and Herukka, Sanna Kaisa and Johannsen, Peter and van Laere, Koen and de Leon, Mony J. and Maier, Wolfgang and Marcusson, Jan and Meulenbroek, Olga and Møllergård, Hanne M. and Morris, John C. and Mroczko, Barbara and Nordlund, Arto and Prabhakar, Sudesh and Peters, Oliver and Rami, Lorena and Rodríguez-Rodríguez, Eloy and Roe, Catherine M. and Rüther, Eckart and Santana, Isabel and Schröder, Johannes and Seo, Sang W. and Soininen, Hilkka and Spiru, Luiza and Stomrud, Erik and Struyfs, Hanne and Teunissen, Charlotte E. and Verhey, Frans R.J. and Vos, Stephanie J.B. and van Waalwijk van Doorn, Linda J.C. and Waldemar, Gunhild and Wallin, Åsa K. and Wiltfang, Jens and Vandenberghe, Rik and Brooks, David J. and Fladby, Tormod and Rowe, Christopher C. and Drzezga, Alexander and Verbeek, Marcel M. and Sarazin, Marie and Wolk, David A. and Fleisher, Adam S. and Klunk, William E. and Na, Duk L. and Sánchez-Juan, Pascual and Lee, Dong Young and Nordberg, Agneta and Tsolaki, Magda and Camus, Vincent and Rinne, Juha O. and Fagan, Anne M. and Zetterberg, Henrik and Blennow, Kaj and Rabinovici, Gil D. and Hansson, Oskar and van Berckel, Bart N.M. and van der Flier, Wiesje M. and Scheltens, Philip and Visser, Pieter Jelle and Ossenkoppele, Rik},
  issn         = {1552-5260},
  keyword      = {Age,Alzheimer's disease,Amyloid,APOE,CSF,Education,Geographical location,Mild cognitive impairment,PET,Prevalence,Sex,Subjective cognitive decline},
  language     = {eng},
  number       = {7},
  pages        = {913--924},
  publisher    = {Elsevier},
  series       = {Alzheimer's and Dementia},
  title        = {Prevalence of the apolipoprotein E ε4 allele in amyloid β positive subjects across the spectrum of Alzheimer's disease},
  url          = {http://dx.doi.org/10.1016/j.jalz.2018.02.009},
  volume       = {14},
  year         = {2018},
}