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 Popp; Pauline 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

doi:https://doi.org/10.1016/j.jalz.2018.02.009

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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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 language	English
Pages (from-to)	913-924
Number of pages	12
Journal	Alzheimer's and 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
Age
Alzheimer's disease
Amyloid
CSF
Education
Geographical location
Mild cognitive impairment
PET
Prevalence
Sex
Subjective cognitive decline

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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., Chételat, G., Resende de Oliveira, C., Rodrigue, K. M., Kornhuber, J., Wallin, A., Klimkowicz-Mrowiec, A., Kandimalla, R., ... Ossenkoppele, R. (2018). Prevalence of the apolipoprotein E ε4 allele in amyloid β positive subjects across the spectrum of Alzheimer's disease. Alzheimer's and Dementia, 14(7), 913-924. https://doi.org/10.1016/j.jalz.2018.02.009

@article{536cc507654e42df9b45c7667466ad7c,

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

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.",

keywords = "APOE, Age, Alzheimer's disease, Amyloid, CSF, Education, Geographical location, Mild cognitive impairment, PET, Prevalence, Sex, Subjective cognitive decline",

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, {Jos{\'e} Luis} and Jagust, {William J.} and Frisoni, {Giovanni B.} and Adrian Ivanoiu and Ga{\"e}l Ch{\'e}telat and {Resende de Oliveira}, Catarina 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 In{\^e}s Baldeiras and {van Buchem}, {Mark A.} and Enrica Cavedo and Kewei Chen and Cohen, {Ann D.} and Stefan F{\"o}rster 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 Herukka, {Sanna Kaisa} and Peter Johannsen and {van Laere}, Koen and {de Leon}, {Mony J.} and Wolfgang Maier and Jan Marcusson and Olga Meulenbroek and M{\o}llerg{\aa}rd, {Hanne M.} and Morris, {John C.} and Barbara Mroczko and Arto Nordlund and Sudesh Prabhakar and Oliver Peters and Lorena Rami and Eloy Rodr{\'i}guez-Rodr{\'i}guez and Roe, {Catherine M.} and Eckart R{\"u}ther and Isabel Santana and Johannes Schr{\"o}der 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 {van Waalwijk van Doorn}, {Linda J.C.} and Gunhild Waldemar and Wallin, {{\AA}sa 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 S{\'a}nchez-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 {van Berckel}, {Bart N.M.} and {van der Flier}, {Wiesje M.} and Philip Scheltens and Visser, {Pieter Jelle} and Rik Ossenkoppele",

year = "2018",

month = jul,

day = "1",

doi = "https://doi.org/10.1016/j.jalz.2018.02.009",

language = "English",

volume = "14",

pages = "913--924",

journal = "Alzheimer's and Dementia",

issn = "1552-5260",

publisher = "Elsevier 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, Chételat, G, Resende de Oliveira, C, Rodrigue, KM, Kornhuber, J, Wallin, A, Klimkowicz-Mrowiec, A, Kandimalla, R, Popp, J, Aalten, PP, Aarsland, D, Alcolea, D, Almdahl, IS, Baldeiras, I, van Buchem, MA, Cavedo, E, Chen, K, Cohen, AD, Förster, S, Fortea, J, Frederiksen, KS, Freund-Levi, Y, Gill, KD, Gkatzima, O, Grimmer, T, Hampel, H, Herukka, SK, Johannsen, P, van Laere, K, de Leon, MJ, Maier, W, Marcusson, J, Meulenbroek, O, Møllergård, HM, Morris, JC, Mroczko, B, Nordlund, A, Prabhakar, S, Peters, O, Rami, L, Rodríguez-Rodríguez, E, Roe, CM, Rüther, E, Santana, I, Schröder, J, Seo, SW, Soininen, H, Spiru, L, Stomrud, E, Struyfs, H, Teunissen, CE, Verhey, FRJ, Vos, SJB, van Waalwijk van Doorn, LJC, Waldemar, G, Wallin, ÅK, Wiltfang, J, Vandenberghe, R, Brooks, DJ, Fladby, T, Rowe, CC, Drzezga, A, Verbeek, MM, Sarazin, M, Wolk, DA, Fleisher, AS, Klunk, WE, Na, DL, Sánchez-Juan, P, Lee, DY, Nordberg, A, Tsolaki, M, Camus, V, Rinne, JO, Fagan, AM, Zetterberg, H, Blennow, K, Rabinovici, GD, Hansson, O, van Berckel, BNM , van der Flier, WM , Scheltens, P , Visser, PJ & Ossenkoppele, R 2018, 'Prevalence of the apolipoprotein E ε4 allele in amyloid β positive subjects across the spectrum of Alzheimer's disease', Alzheimer's and 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 ε4 allele in amyloid β 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, José Luis

AU - Jagust, William J.

AU - Frisoni, Giovanni B.

AU - Ivanoiu, Adrian

AU - Chételat, Gaël

AU - Resende de Oliveira, Catarina

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, Inês

AU - van Buchem, Mark A.

AU - Cavedo, Enrica

AU - Chen, Kewei

AU - Cohen, Ann D.

AU - Förster, 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 - van Laere, Koen

AU - de Leon, Mony J.

AU - Maier, Wolfgang

AU - Marcusson, Jan

AU - Meulenbroek, Olga

AU - Møllergård, Hanne M.

AU - Morris, John C.

AU - Mroczko, Barbara

AU - Nordlund, Arto

AU - Prabhakar, Sudesh

AU - Peters, Oliver

AU - Rami, Lorena

AU - Rodríguez-Rodríguez, Eloy

AU - Roe, Catherine M.

AU - Rüther, Eckart

AU - Santana, Isabel

AU - Schröder, 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 - van Waalwijk van Doorn, Linda J.C.

AU - Waldemar, Gunhild

AU - Wallin, Åsa 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 - Sánchez-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 - van Berckel, Bart N.M.

AU - van der 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) 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.

AB - 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.

KW - APOE

KW - Age

KW - Alzheimer's disease

KW - Amyloid

KW - CSF

KW - Education

KW - Geographical location

KW - Mild cognitive impairment

KW - PET

KW - Prevalence

KW - Sex

KW - Subjective cognitive decline

UR - http://www.scopus.com/inward/record.url?scp=85045929153&partnerID=8YFLogxK

U2 - https://doi.org/10.1016/j.jalz.2018.02.009

DO - https://doi.org/10.1016/j.jalz.2018.02.009

M3 - Article

C2 - 29601787

SN - 1552-5260

VL - 14

SP - 913

EP - 924

JO - Alzheimer's and Dementia

JF - Alzheimer's and Dementia

IS - 7

ER -

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

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