Prevalence of the apolipoprotein E epsilon 4 allele in amyloid beta positive subjects across the spectrum of Alzheimer's disease
Por:
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, SK, 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, WMD, Scheltens, P, Visser, PJ, Ossenkoppele, R
Publicada:
1 jul 2018
Resumen:
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.
Filiaciones:
Mattsson, N:
Lund Univ, Clin Sci Malmo, Clin Memory Res Unit, Lund, Sweden
Groot, C:
Vrije Univ Amsterdam, Med Ctr, Dept Neurol, Neurosci Campus Amsterdam, Amsterdam, Netherlands
Vrije Univ Amsterdam, Med Ctr, Alzheimer Ctr, Neurosci Campus Amsterdam, Amsterdam, Netherlands
Jansen, WJ:
Maastricht Univ, Alzheimer Ctr Limburg, Sch Mental Hlth & Neurosci, Dept Psychiat & Neuropsychol, Maastricht, Netherlands
Landau, SM:
Univ Calif Berkeley, Helen Wills Neurosci Inst, Berkeley, CA 94720 USA
Villemagne, VL:
Austin Hlth, Dept Nucl Med, Melbourne, Vic, Australia
Austin Hlth, Ctr PET, Melbourne, Vic, Australia
Engelborghs, S:
Univ Antwerp, Reference Ctr Biol Markers Dementia BIODEM, Antwerp, Belgium
Mintun, MM:
Avid Radiopharmaceut, Philadelphia, PA USA
Lleo, A:
Hosp Santa Creu & Sant Pau, Neurol Dept, Barcelona, Spain
Molinuevo, JL:
Clin Univ Hosp, Alzheimers Dis & Other Cognit Disorders Unit, IDIBAPS, Barcelona, Spain
Jagust, WJ:
Univ Calif Berkeley, Helen Wills Neurosci Inst, Berkeley, CA 94720 USA
Frisoni, GB:
Univ Hosp, Memory Clin, Geneva, Switzerland
Univ Hosp, Lab Neuroimaging Aging, LANVIE, Geneva, Switzerland
Univ Geneva, Geneva, Switzerland
IRCCS, Ctr San Giovanni Dio Fatebenefratelli, Lab Alzheimers Neuroimaging & Epidemiol, Brescia, Italy
Ivanoiu, A:
Clin Univ Hosp, Alzheimers Dis & Other Cognit Disorders Unit, IDIBAPS, Barcelona, Spain
Catholic Univ Louvain, St Luc Univ Hosp, Inst Neurosci, Memory Clin, Brussels, Belgium
Catholic Univ Louvain, St Luc Univ Hosp, Inst Neurosci, Neurochem Lab, Brussels, Belgium
Chetelat, G:
Univ Caen Normandie, INSERM, GIP Cyceron, UMR S U1237, Caen, France
Oliveira, CR:
CHU Coimbra, Fac Med, Ctr Neurosci & Cell Biol, Coimbra, Portugal
Rodrigue, KM:
Univ Texas Dallas, Sch Behav & Brain Sci, Ctr Vital Longev, Dallas, TX USA
Kornhuber, J:
Friedrich Alexander Univ Erlangen Nuremberg, Dept Psychiat & Psychotherapy, Erlangen, Germany
Wallin, A:
Lund Univ, Clin Sci Malmo, Clin Memory Res Unit, Lund, Sweden
Univ Gothenburg, Sahlgrenska Acad, Inst Neurosci & Physiol, Molndal, Sweden
Klimkowicz-Mrowiec, A:
Jagiellonian Univ, Coll Med, Krakow, Poland
Kandimalla, R:
Postgrad Inst Med Educ & Res PGIMER, Dept Biochem, Chandigarh, India
Popp, J:
Univ Hosp Lausanne, Serv Old Age Psychiat, Dept Psychiat, Lausanne, Switzerland
Aalten, PP:
Maastricht Univ, Alzheimer Ctr Limburg, Sch Mental Hlth & Neurosci, Dept Psychiat & Neuropsychol, Maastricht, Netherlands
Aarsland, D:
Stavanger Univ Hosp, Ctr Age Related Med, Stavanger, Norway
Alcolea, D:
Hosp Santa Creu & Sant Pau, Neurol Dept, Barcelona, Spain
Almdahl, IS:
Akershus Univ Hosp, Dept Neurol, Lorenskog, Norway
Baldeiras, I:
CHU Coimbra, Fac Med, Ctr Neurosci & Cell Biol, Coimbra, Portugal
Buchem, MA:
Leiden Univ, Med Ctr, Dept Radiol, Leiden, Netherlands
Cavedo, E:
IRCCS, Ctr San Giovanni Dio Fatebenefratelli, Lab Alzheimers Neuroimaging & Epidemiol, Brescia, Italy
Univ Pierre & Marie Curie UPMC Paris 06, Sorbonne Univ,AXA Res Fund & UPMC Chair, INSERM,Inst Mem & Maladie dAlzheimer IM2A,Hop Pit, CNRS,Inst Cerveau & Moelle Epiniere ICM,Dept Neur, Paris, France
Chen, K:
Banner Alzheimers Inst, Phoenix, AZ USA
Cohen, AD:
Univ Pittsburgh, Sch Med, Dept Psychiat, Pittsburgh, PA USA
Foerster, S:
Tech Univ Munich, Dept Nucl Med, Munich, Germany
Fortea, J:
Hosp Santa Creu & Sant Pau, Neurol Dept, Barcelona, Spain
Frederiksen, KS:
Univ Copenhagen, Rigshosp, Dept Neurol, Danish Dementia Res Ctr, Copenhagen, Denmark
Freund-Levi, Y:
Karolinska Univ, Hosp Huddinge, Karolinska Inst, Sect Clin Geriatr,Inst NVS,Dept Geriatr, Stockholm, Sweden
Gill, KD:
Postgrad Inst Med Educ & Res PGIMER, Dept Biochem, Chandigarh, India
Gkatzima, O:
Aristotle Univ Thessaloniki, Dept Neurol 3, Thessaloniki, Greece
Grimmer, T:
Techn Univ Munchen, Klinikum Rechts Isar, Dept Psychiat & Psychotherapy, Munich, Germany
Hampel, H:
Univ Pierre & Marie Curie UPMC Paris 06, Sorbonne Univ,AXA Res Fund & UPMC Chair, INSERM,Inst Mem & Maladie dAlzheimer IM2A,Hop Pit, CNRS,Inst Cerveau & Moelle Epiniere ICM,Dept Neur, Paris, France
Ludwig Maximilians Univ Munchen, Alzheimer Mem Ctr, Dept Psychiat, Munich, Germany
Ludwig Maximilians Univ Munchen, Geriatr Psychiat Branch, Munich, Germany
Herukka, SK:
Univ Eastern Finland, Dept Neurol, Kuopio, Finland
Kuopio Univ Hosp, Kuopio, Finland
Johannsen, P:
Rigshosp, Danish Dementia Res Ctr, Memory Clin, Copenhagen, Denmark
Laere, K:
Katholieke Univ Leuven, Dept Imaging & Pathol, Leuven, Belgium
Leon, MJ:
NYU, Ctr Brain Hlth, Sch Med, New York, NY USA
Maier, W:
Univ Bonn, German Ctr Neurodegenerat Dis DZNE, Dept Psychiat & Psychotherapy, Bonn, Germany
Marcusson, J:
Univ Linkoping, Dept Clin & Expt Med, Geriatr Med, Linkoping, Sweden
Meulenbroek, O:
Radboud Univ Nijmegen, Med Ctr, Radboud Alzheimer Ctr, Dept Geriatr Med, Nijmegen, Netherlands
Mollergard, HM:
Akershus Univ Hosp, Dept Neurol, Lorenskog, Norway
Morris, JC:
Washington Univ, Sch Med, Dept Neurol, Knight Alzheimers Dis Res Ctr, St Louis, MO 63110 USA
Mroczko, B:
Med Univ Bialystok, Leading Natl Res Ctr Bialystok KNOW, Dept Neurodegenerat Diagnost, Bialystok, Poland
Nordlund, A:
Univ Gothenburg, Sahlgrenska Acad, Inst Neurosci & Physiol, Molndal, Sweden
Prabhakar, S:
Postgrad Inst Med Educ & Res PGIMER, Dept Neurol, Chandigarh, India
Peters, O:
German Ctr Neurodegenerat Dis DZNE, Dept Psychiat & Psychotherapy, Berlin, Germany
Rami, L:
Clin Univ Hosp, Alzheimers Dis & Other Cognit Disorders Unit, IDIBAPS, Barcelona, Spain
Rodriguez-Rodriguez, E:
Univ Hosp Marques Valdecilla, IDIVAL, CIBERNED, Neurol Serv, Santander, Spain
Roe, CM:
Washington Univ, Sch Med, Dept Neurol, Knight Alzheimers Dis Res Ctr, St Louis, MO 63110 USA
Ruther, E:
Georg August Univ, Univ Med Ctr, Dept Psychiat & Psychotherapy, Gottingen, Germany
Santana, I:
CHU Coimbra, Fac Med, Ctr Neurosci & Cell Biol, Coimbra, Portugal
Schroder, J:
Heidelberg Univ, Sekt Gerontopsychiat, Heidelberg, Germany
Seo, SW:
Sungkyunkwan Univ, Sch Med, Samsung Med Ctr, Dept Neurol, Seoul, South Korea
Soininen, H:
Univ Eastern Finland, Dept Neurol, Kuopio, Finland
Kuopio Univ Hosp, Kuopio, Finland
Spiru, L:
Carol Davila Univ Med & Pharm, Dept Geriatr Gerontol Gerontopsychiat, Bucharest, Romania
Stomrud, E:
Lund Univ, Clin Sci Malmo, Clin Memory Res Unit, Lund, Sweden
Struyfs, H:
Univ Antwerp, Reference Ctr Biol Markers Dementia BIODEM, Antwerp, Belgium
Teunissen, CE:
Vrije Univ Amsterdam, Med Ctr, Amsterdam Neurosci, Dept Clin Chem,Neurochem Lab, Amsterdam, Netherlands
Vrije Univ Amsterdam, Med Ctr, Amsterdam Neurosci, Dept Clin Chem,Biobank, Amsterdam, Netherlands
Verhey, FRJ:
Maastricht Univ, Alzheimer Ctr Limburg, Sch Mental Hlth & Neurosci, Dept Psychiat & Neuropsychol, Maastricht, Netherlands
Vos, SJB:
Maastricht Univ, Alzheimer Ctr Limburg, Sch Mental Hlth & Neurosci, Dept Psychiat & Neuropsychol, Maastricht, Netherlands
Doorn, LJCVW:
Radboud Univ Nijmegen, Med Ctr, Radboud Alzheimer Ctr, Donders Inst Brain Cognit & Behav,Dept Neurol, Nijmegen, Netherlands
Radboud Univ Nijmegen, Med Ctr, Radboud Alzheimer Ctr, Donders Inst Brain Cognit & Behav,Dept Lab Med, Nijmegen, Netherlands
Waldemar, G:
Univ Copenhagen, Rigshosp, Dept Neurol, Danish Dementia Res Ctr, Copenhagen, Denmark
Wallin, AK:
Lund Univ, Clin Sci Malmo, Clin Memory Res Unit, Lund, Sweden
Wiltfang, J:
Georg August Univ, Univ Med Ctr, Dept Psychiat & Psychotherapy, Gottingen, Germany
Vandenberghe, R:
Katholieke Univ Leuven, KU Leuven, Lab Cognit Neurol, Leuven, Belgium
Katholieke Univ Leuven, KU Leuven, Alzheimer Res Ctr, Leuven, Belgium
Brooks, DJ:
Imperial Coll London, Clin Sci Ctr, Med Res Council, Div Neurosci, London, England
Fladby, T:
Akershus Univ Hosp, Dept Neurol, Lorenskog, Norway
Rowe, CC:
Austin Hlth, Dept Nucl Med, Melbourne, Vic, Australia
Austin Hlth, Ctr PET, Melbourne, Vic, Australia
Drzezga, A:
Univ Cologne, Dept Nucl Med, Cologne, Germany
Verbeek, MM:
Radboud Univ Nijmegen, Med Ctr, Radboud Alzheimer Ctr, Donders Inst Brain Cognit & Behav,Dept Neurol, Nijmegen, Netherlands
Radboud Univ Nijmegen, Med Ctr, Radboud Alzheimer Ctr, Donders Inst Brain Cognit & Behav,Dept Lab Med, Nijmegen, Netherlands
Sarazin, M:
Sorbonne Paris Cite, Univ Paris Descartes, Ctr Hospitalier St Anne, Neurol Memoire & Langage, Paris, France
Wolk, DA:
Univ Penn, Dept Neurol, Philadelphia, PA 19104 USA
Fleisher, AS:
Banner Alzheimers Inst, Phoenix, AZ USA
Eli Lilly, Indianapolis, IN USA
Univ Calif San Diego, Dept Neurosci, San Diego, CA 92103 USA
Klunk, WE:
Univ Pittsburgh, Sch Med, Dept Psychiat, Pittsburgh, PA USA
Na, DL:
Sungkyunkwan Univ, Sch Med, Samsung Med Ctr, Dept Neurol, Seoul, South Korea
Sanchez-Juan, P:
Univ Hosp Marques Valdecilla, IDIVAL, CIBERNED, Neurol Serv, Santander, Spain
Lee, DY:
Seoul Natl Univ, Coll Med, Dept Neuropsychiat, Seoul, South Korea
Nordberg, A:
Karolinska Univ Hosp, Karolinska Inst & Geriatr Med, Translat Alzheimer Neurobiol, Ctr Alzheimer Res,Dept NVS, Stockholm, Sweden
Tsolaki, M:
Aristotle Univ Thessaloniki, Dept Neurol 3, Thessaloniki, Greece
Camus, V:
Univ Francois Rabelais Tours, CHRU Tours, INSERM, CIC 1415,U930, Tours, France
Rinne, JO:
Univ Turku, Turku PET Ctr, Turku, Finland
Univ Turku, Div Clin Neurosci Turku, Turku, Finland
Turku Univ Hosp, Turku, Finland
Fagan, AM:
Washington Univ, Sch Med, Dept Neurol, Knight Alzheimers Dis Res Ctr, St Louis, MO 63110 USA
Zetterberg, H:
UCL, Inst Neurol, Dept Mol Neurosci, Queen Sq, London, England
UK Dementia Res Inst, London, England
Univ Gothenburg, Sahlgrenska Acad, Dept Psychiat & Neurochem, Inst Neurosci & Physiol, Molndal, Sweden
Sahlgrens Univ Hosp, Sweden & Clin Neurochem Lab, Molndal, Sweden
Blennow, K:
Univ Gothenburg, Sahlgrenska Acad, Dept Psychiat & Neurochem, Inst Neurosci & Physiol, Molndal, Sweden
Sahlgrens Univ Hosp, Sweden & Clin Neurochem Lab, Molndal, Sweden
Rabinovici, GD:
Univ Calif San Francisco, Memory & Aging Ctr, Dept Neurol, San Francisco, CA 94143 USA
Hansson, O:
Lund Univ, Clin Sci Malmo, Clin Memory Res Unit, Lund, Sweden
Berckel, BNM:
Vrije Univ Amsterdam, Med Ctr, Dept Radiol & Nucl Med, Neurosci Campus Amsterdam, Amsterdam, Netherlands
Flier, WMD:
Vrije Univ Amsterdam, Med Ctr, Dept Neurol, Neurosci Campus Amsterdam, Amsterdam, Netherlands
Vrije Univ Amsterdam, Med Ctr, Alzheimer Ctr, Neurosci Campus Amsterdam, Amsterdam, Netherlands
Vrije Univ Amsterdam, Med Ctr, Dept Epidemiol & Biostat, Amsterdam, Netherlands
Scheltens, P:
Vrije Univ Amsterdam, Med Ctr, Dept Neurol, Neurosci Campus Amsterdam, Amsterdam, Netherlands
Vrije Univ Amsterdam, Med Ctr, Alzheimer Ctr, Neurosci Campus Amsterdam, Amsterdam, Netherlands
Visser, PJ:
Vrije Univ Amsterdam, Med Ctr, Dept Neurol, Neurosci Campus Amsterdam, Amsterdam, Netherlands
Vrije Univ Amsterdam, Med Ctr, Alzheimer Ctr, Neurosci Campus Amsterdam, Amsterdam, Netherlands
Maastricht Univ, Alzheimer Ctr Limburg, Sch Mental Hlth & Neurosci, Dept Psychiat & Neuropsychol, Maastricht, Netherlands
Ossenkoppele, R:
Lund Univ, Clin Sci Malmo, Clin Memory Res Unit, Lund, Sweden
Vrije Univ Amsterdam, Med Ctr, Dept Neurol, Neurosci Campus Amsterdam, Amsterdam, Netherlands
Vrije Univ Amsterdam, Med Ctr, Alzheimer Ctr, Neurosci Campus Amsterdam, Amsterdam, Netherlands
Vrije Univ Amsterdam, Med Ctr, Dept Radiol & Nucl Med, Neurosci Campus Amsterdam, Amsterdam, Netherlands
Green Published, Green Accepted
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