Prevalence of the apolipoprotein E epsilon 4 allele in amyloid beta 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; Jose Luis Molinuevo; William J. Jagust; Giovanni B. Frisoni; Adrian Ivanoiu; Gael Chetelat; Catarina Resende Oliveira; Karen M. Rodrigue; Johannes Kornhuber; Anders Wallin; Aleksandra Klimkowicz-Mrowiec; Ramesh Kandimalla; Julius Popp; Pauline P. Aalten; Dag Aarsland; Daniel Alcolea; Ina S. Almdahl; Ines Baldeiras; Mark A. Buchem; Enrica Cavedo; Kewei Chen; Ann D. Cohen; Stefan Foerster; Juan Fortea; Kristian S. Frederiksen; Yvonne Freund-Levi; Kiran Dip Gill; Olymbia Gkatzima; Timo Grimmer; Harald Hampel; Sanna-Kaisa Herukka; Peter Johannsen; Koen Laere; Mony J. Leon; Wolfgang Maier; Jan Marcusson; Olga Meulenbroek; Hanne M. Mollergard; John C. Morris; Barbara Mroczko; Arto Nordlund; Sudesh Prabhakar; Oliver Peters; Lorena Rami; Eloy Rodriguez-Rodriguez; Catherine M. Roe; Eckart Ruther; Isabel Santana; Johannes Schroder; 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 Doorn; Gunhild Waldemar; Asa 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 Sanchez-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. Berckel; Wiesje M. Flier; Philip Scheltens; Pieter Jelle Visser; Rik Ossenkoppele

doi:10.1016/j.jalz.2018.02.009

Prevalence of the apolipoprotein E epsilon 4 allele in amyloid beta 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
, Jose Luis Molinuevo
, William J. Jagust
, Giovanni B. Frisoni
, Adrian Ivanoiu
, Gael Chetelat
, Catarina Resende Oliveira
, Karen M. Rodrigue
, Johannes Kornhuber
, Anders Wallin
, Aleksandra Klimkowicz-Mrowiec
, Ramesh Kandimalla
, Julius Popp

Pauline P. Aalten, Dag Aarsland, Daniel Alcolea, Ina S. Almdahl, Ines Baldeiras, Mark A. Buchem, Enrica Cavedo, Kewei Chen, Ann D. Cohen, Stefan Foerster, Juan Fortea, Kristian S. Frederiksen, Yvonne Freund-Levi, Kiran Dip Gill, Olymbia Gkatzima, Timo Grimmer, Harald Hampel, Sanna-Kaisa Herukka, Peter Johannsen, Koen Laere, Mony J. Leon, Wolfgang Maier, Jan Marcusson, Olga Meulenbroek, Hanne M. Mollergard, John C. Morris, Barbara Mroczko, Arto Nordlund, Sudesh Prabhakar, Oliver Peters, Lorena Rami, Eloy Rodriguez-Rodriguez, Catherine M. Roe, Eckart Ruther, Isabel Santana, Johannes Schroder, 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 Doorn, Gunhild Waldemar, Asa 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 Sanchez-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. Berckel, Wiesje M. Flier, Philip Scheltens, Pieter Jelle Visser, Rik Ossenkoppele^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › Academic › peer-review

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Abstract

Introduction: Apolipoprotein E (APOE) epsilon 4 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 beta(A beta) pathology. Methods: We included 3451 A beta+ subjects (853 AD-type dementia, 1810 mild cognitive impairment, and 788 cognitively normal). Generalized estimating equation models were used to assess APOE epsilon 4 prevalence in relation to age, sex, education, and geographical location. Results: The APOE epsilon 4 prevalence was 66% in AD-type dementia, 64% in mild cognitive impairment, and 51% in cognitively normal, and it decreased with advancing age in A beta+ cognitively normal and A beta+ mild cognitive impairment (P <.05) but not in A beta+ AD dementia (P =.66). The prevalence was highest in Northern Europe but did not vary by sex or education. Discussion: The APOE E4 prevalence in AD was higher than that in previous studies, which did not require presence of A beta pathology. Furthermore, our results highlight disease heterogeneity related to age and geographical location. (C) 2018 the Alzheimer's Association. Published by Elsevier Inc. All rights reserved.

Original language	English
Pages (from-to)	913-924
Number of pages	12
Journal	Alzheimer's & Dementia
Volume	14
Issue number	7
DOIs	https://doi.org/10.1016/j.jalz.2018.02.009
Publication status	Published - 1 Jul 2018

Keywords

APOE
Prevalence
Amyloid
PET
CSF
Alzheimer's disease
Mild cognitive impairment
Subjective cognitive decline
Age
Sex
Education
Geographical location
CEREBROSPINAL-FLUID BIOMARKERS
MILD COGNITIVE IMPAIRMENT
NATIONAL INSTITUTE
APOE GENOTYPE
ASSOCIATION WORKGROUPS
DIAGNOSTIC GUIDELINES
LONGITUDINAL COHORT
GLUCOSE-METABOLISM
CSF BIOMARKERS
OLDER-ADULTS

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Mattsson, N., Groot, C., Jansen, W. J., Landau, S. M., Villemagne, V. L., Engelborghs, S., Mintun, M. M., Lleo, A., Molinuevo, J. L., Jagust, W. J., Frisoni, G. B., Ivanoiu, A., Chetelat, G., Oliveira, C. R., Rodrigue, K. M., Kornhuber, J., Wallin, A., Klimkowicz-Mrowiec, A., Kandimalla, R., ... Ossenkoppele, R. (2018). Prevalence of the apolipoprotein E epsilon 4 allele in amyloid beta positive subjects across the spectrum of Alzheimer's disease. Alzheimer's & Dementia, 14(7), 913-924. https://doi.org/10.1016/j.jalz.2018.02.009

@article{92b805245bd5497c9a77b40e55d2a194,

title = "Prevalence of the apolipoprotein E epsilon 4 allele in amyloid beta positive subjects across the spectrum of Alzheimer's disease",

abstract = "Introduction: Apolipoprotein E (APOE) epsilon 4 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 beta(A beta) pathology. Methods: We included 3451 A beta+ subjects (853 AD-type dementia, 1810 mild cognitive impairment, and 788 cognitively normal). Generalized estimating equation models were used to assess APOE epsilon 4 prevalence in relation to age, sex, education, and geographical location. Results: The APOE epsilon 4 prevalence was 66\% in AD-type dementia, 64\% in mild cognitive impairment, and 51\% in cognitively normal, and it decreased with advancing age in A beta+ cognitively normal and A beta+ mild cognitive impairment (P <.05) but not in A beta+ AD dementia (P =.66). The prevalence was highest in Northern Europe but did not vary by sex or education. Discussion: The APOE E4 prevalence in AD was higher than that in previous studies, which did not require presence of A beta pathology. Furthermore, our results highlight disease heterogeneity related to age and geographical location. (C) 2018 the Alzheimer's Association. Published by Elsevier Inc. All rights reserved.",

keywords = "APOE, Prevalence, Amyloid, PET, CSF, Alzheimer's disease, Mild cognitive impairment, Subjective cognitive decline, Age, Sex, Education, Geographical location, CEREBROSPINAL-FLUID BIOMARKERS, MILD COGNITIVE IMPAIRMENT, NATIONAL INSTITUTE, APOE GENOTYPE, ASSOCIATION WORKGROUPS, DIAGNOSTIC GUIDELINES, LONGITUDINAL COHORT, GLUCOSE-METABOLISM, CSF BIOMARKERS, OLDER-ADULTS",

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

year = "2018",

month = jul,

day = "1",

doi = "10.1016/j.jalz.2018.02.009",

language = "English",

volume = "14",

pages = "913--924",

journal = "Alzheimer's \& Dementia",

issn = "1552-5260",

publisher = "John Wiley \& Sons Inc.",

number = "7",

}

Mattsson, N, Groot, C, Jansen, WJ, Landau, SM, Villemagne, VL, Engelborghs, S, Mintun, MM, Lleo, A, Molinuevo, JL, Jagust, WJ, Frisoni, GB, Ivanoiu, A, Chetelat, G, Oliveira, CR, Rodrigue, KM, Kornhuber, J, Wallin, A, Klimkowicz-Mrowiec, A, Kandimalla, R, Popp, J, Aalten, PP, Aarsland, D, Alcolea, D, Almdahl, IS, Baldeiras, I, Buchem, MA, Cavedo, E, Chen, K, Cohen, AD, Foerster, S, Fortea, J, Frederiksen, KS, Freund-Levi, Y, Gill, KD, Gkatzima, O, Grimmer, T, Hampel, H, Herukka, S-K, Johannsen, P, Laere, K, Leon, MJ, Maier, W, Marcusson, J, Meulenbroek, O, Mollergard, HM, Morris, JC, Mroczko, B, Nordlund, A, Prabhakar, S, Peters, O, Rami, L, Rodriguez-Rodriguez, E, Roe, CM, Ruther, E, Santana, I, Schroder, J, Seo, SW, Soininen, H, Spiru, L, Stomrud, E, Struyfs, H, Teunissen, CE, Verhey, FRJ , Vos, SJB, Doorn, LJCVW, Waldemar, G, Wallin, AK, Wiltfang, J, Vandenberghe, R, Brooks, DJ, Fladby, T, Rowe, CC, Drzezga, A, Verbeek, MM, Sarazin, M, Wolk, DA, Fleisher, AS, Klunk, WE, Na, DL, Sanchez-Juan, P, Lee, DY, Nordberg, A, Tsolaki, M, Camus, V, Rinne, JO, Fagan, AM, Zetterberg, H, Blennow, K, Rabinovici, GD, Hansson, O, Berckel, BNM, Flier, WM, Scheltens, P, Visser, PJ & Ossenkoppele, R 2018, 'Prevalence of the apolipoprotein E epsilon 4 allele in amyloid beta positive subjects across the spectrum of Alzheimer's disease', Alzheimer's & Dementia, vol. 14, no. 7, pp. 913-924. https://doi.org/10.1016/j.jalz.2018.02.009

TY - JOUR

T1 - Prevalence of the apolipoprotein E epsilon 4 allele in amyloid beta positive subjects across the spectrum of Alzheimer's disease

AU - Mattsson, Niklas

AU - Groot, Colin

AU - Jansen, Willemijn J.

AU - Landau, Susan M.

AU - Villemagne, Victor L.

AU - Engelborghs, Sebastiaan

AU - Mintun, Mark M.

AU - Lleo, Alberto

AU - Molinuevo, Jose Luis

AU - Jagust, William J.

AU - Frisoni, Giovanni B.

AU - Ivanoiu, Adrian

AU - Chetelat, Gael

AU - Oliveira, Catarina Resende

AU - Rodrigue, Karen M.

AU - Kornhuber, Johannes

AU - Wallin, Anders

AU - Klimkowicz-Mrowiec, Aleksandra

AU - Kandimalla, Ramesh

AU - Popp, Julius

AU - Aalten, Pauline P.

AU - Aarsland, Dag

AU - Alcolea, Daniel

AU - Almdahl, Ina S.

AU - Baldeiras, Ines

AU - Buchem, Mark A.

AU - Cavedo, Enrica

AU - Chen, Kewei

AU - Cohen, Ann D.

AU - Foerster, Stefan

AU - Fortea, Juan

AU - Frederiksen, Kristian S.

AU - Freund-Levi, Yvonne

AU - Gill, Kiran Dip

AU - Gkatzima, Olymbia

AU - Grimmer, Timo

AU - Hampel, Harald

AU - Herukka, Sanna-Kaisa

AU - Johannsen, Peter

AU - Laere, Koen

AU - Leon, Mony J.

AU - Maier, Wolfgang

AU - Marcusson, Jan

AU - Meulenbroek, Olga

AU - Mollergard, Hanne M.

AU - Morris, John C.

AU - Mroczko, Barbara

AU - Nordlund, Arto

AU - Prabhakar, Sudesh

AU - Peters, Oliver

AU - Rami, Lorena

AU - Rodriguez-Rodriguez, Eloy

AU - Roe, Catherine M.

AU - Ruther, Eckart

AU - Santana, Isabel

AU - Schroder, Johannes

AU - Seo, Sang W.

AU - Soininen, Hilkka

AU - Spiru, Luiza

AU - Stomrud, Erik

AU - Struyfs, Hanne

AU - Teunissen, Charlotte E.

AU - Verhey, Frans R. J.

AU - Vos, Stephanie J. B.

AU - Doorn, Linda J. C. van Waalwijk

AU - Waldemar, Gunhild

AU - Wallin, Asa K.

AU - Wiltfang, Jens

AU - Vandenberghe, Rik

AU - Brooks, David J.

AU - Fladby, Tormod

AU - Rowe, Christopher C.

AU - Drzezga, Alexander

AU - Verbeek, Marcel M.

AU - Sarazin, Marie

AU - Wolk, David A.

AU - Fleisher, Adam S.

AU - Klunk, William E.

AU - Na, Duk L.

AU - Sanchez-Juan, Pascual

AU - Lee, Dong Young

AU - Nordberg, Agneta

AU - Tsolaki, Magda

AU - Camus, Vincent

AU - Rinne, Juha O.

AU - Fagan, Anne M.

AU - Zetterberg, Henrik

AU - Blennow, Kaj

AU - Rabinovici, Gil D.

AU - Hansson, Oskar

AU - Berckel, Bart N. M.

AU - Flier, Wiesje M.

AU - Scheltens, Philip

AU - Visser, Pieter Jelle

AU - Ossenkoppele, Rik

PY - 2018/7/1

Y1 - 2018/7/1

N2 - Introduction: Apolipoprotein E (APOE) epsilon 4 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 beta(A beta) pathology. Methods: We included 3451 A beta+ subjects (853 AD-type dementia, 1810 mild cognitive impairment, and 788 cognitively normal). Generalized estimating equation models were used to assess APOE epsilon 4 prevalence in relation to age, sex, education, and geographical location. Results: The APOE epsilon 4 prevalence was 66% in AD-type dementia, 64% in mild cognitive impairment, and 51% in cognitively normal, and it decreased with advancing age in A beta+ cognitively normal and A beta+ mild cognitive impairment (P <.05) but not in A beta+ AD dementia (P =.66). The prevalence was highest in Northern Europe but did not vary by sex or education. Discussion: The APOE E4 prevalence in AD was higher than that in previous studies, which did not require presence of A beta pathology. Furthermore, our results highlight disease heterogeneity related to age and geographical location. (C) 2018 the Alzheimer's Association. Published by Elsevier Inc. All rights reserved.

AB - Introduction: Apolipoprotein E (APOE) epsilon 4 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 beta(A beta) pathology. Methods: We included 3451 A beta+ subjects (853 AD-type dementia, 1810 mild cognitive impairment, and 788 cognitively normal). Generalized estimating equation models were used to assess APOE epsilon 4 prevalence in relation to age, sex, education, and geographical location. Results: The APOE epsilon 4 prevalence was 66% in AD-type dementia, 64% in mild cognitive impairment, and 51% in cognitively normal, and it decreased with advancing age in A beta+ cognitively normal and A beta+ mild cognitive impairment (P <.05) but not in A beta+ AD dementia (P =.66). The prevalence was highest in Northern Europe but did not vary by sex or education. Discussion: The APOE E4 prevalence in AD was higher than that in previous studies, which did not require presence of A beta pathology. Furthermore, our results highlight disease heterogeneity related to age and geographical location. (C) 2018 the Alzheimer's Association. Published by Elsevier Inc. All rights reserved.

KW - APOE

KW - Prevalence

KW - Amyloid

KW - PET

KW - CSF

KW - Alzheimer's disease

KW - Mild cognitive impairment

KW - Subjective cognitive decline

KW - Age

KW - Sex

KW - Education

KW - Geographical location

KW - CEREBROSPINAL-FLUID BIOMARKERS

KW - MILD COGNITIVE IMPAIRMENT

KW - NATIONAL INSTITUTE

KW - APOE GENOTYPE

KW - ASSOCIATION WORKGROUPS

KW - DIAGNOSTIC GUIDELINES

KW - LONGITUDINAL COHORT

KW - GLUCOSE-METABOLISM

KW - CSF BIOMARKERS

KW - OLDER-ADULTS

U2 - 10.1016/j.jalz.2018.02.009

DO - 10.1016/j.jalz.2018.02.009

M3 - Article

C2 - 29601787

SN - 1552-5260

VL - 14

SP - 913

EP - 924

JO - Alzheimer's & Dementia

JF - Alzheimer's & Dementia

IS - 7

ER -

Prevalence of the apolipoprotein E epsilon 4 allele in amyloid beta positive subjects across the spectrum of Alzheimer's disease

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