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Alzheimers Dement. 2018 Jul;14(7):913-924. doi: 10.1016/j.jalz.2018.02.009. Epub 2018 Mar 28.

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

Author information

1
Clinical Memory Research Unit, Clinical Sciences Malmö, Lund University, Lund, Sweden. Electronic address: niklas.mattsson@med.lu.se.
2
Department of Neurology and Alzheimer Center, VU University Medical Center, Neuroscience Campus Amsterdam, Amsterdam, the Netherlands.
3
Department of Psychiatry and Neuropsychology, School for Mental Health and Neuroscience, Alzheimer Center Limburg, Maastricht University, Maastricht, the Netherlands.
4
Helen Wills Neuroscience Institute, University of California, Berkeley, CA, USA.
5
Department of Nuclear Medicine and Centre for PET, Austin Health, Melbourne, Australia.
6
Reference Center for Biological Markers of Dementia (BIODEM), University of Antwerp, Antwerp, Belgium.
7
Avid Radiopharmaceuticals, Philadelphia, PA, USA.
8
Neurology Department, Hospital de Sant Pau, Barcelona, Spain.
9
Alzheimer's Disease and Other Cognitive Disorders Unit, IDIBAPS, Clinic University Hospital, Barcelona, Spain.
10
Memory Clinic and LANVIE- Laboratory of Neuroimaging of Aging, University Hospitals, and University of Geneva, Geneva, Switzerland; Laboratory of Alzheimer's Neuroimaging and Epidemiology, IRCCS Centro San Giovanni di Dio Fatebenefratelli, Brescia, Italy.
11
Memory Clinic and Neurochemistry Laboratory, Saint Luc University Hospital, Institute of Neuroscience, Université catholique de Louvain, Brussels, Belgium.
12
Inserm, Inserm UMR-S U1237, Université de Caen-Normandie, GIP Cyceron, Caen, France.
13
Center for Neuroscience and Cell Biology, Faculty of Medicine, Centro Hospitalar e Universitário de Coimbra, Coimbra, Portugal.
14
Center for Vital Longevity, School of Behavioral and Brain Sciences, The University of Texas at Dallas, Dallas, TX, USA.
15
Department of Psychiatry and Psychotherapy, Friedrich-Alexander University of Erlangen- Nuremberg, Erlangen, Germany.
16
Institute of Neuroscience and Physiology, Sahlgrenska Academy at University of Gothenburg, Mölndal, Sweden.
17
Jagiellonian University College of Medicine, Krakow, Poland.
18
Department of Biochemistry, Postgraduate Institute of Medical Education and Research (PGIMER), Chandigarh, India.
19
Department of Psychiatry, Service of Old Age Psychiatry, University Hospital of Lausanne, Lausanne, Switzerland.
20
Center for Age-Related Medicine, Stavanger University Hospital, Stavanger, Norway.
21
Department of Neurology, Akershus University Hospital, Lørenskog, Norway.
22
Department of Radiology, Leiden University Medical Center, Leiden, the Netherlands.
23
Laboratory of Alzheimer's Neuroimaging and Epidemiology, IRCCS Centro San Giovanni di Dio Fatebenefratelli, Brescia, Italy; AXA Research Fund & UPMC Chair, Sorbonne Universités, Université Pierre et Marie Curie (UPMC) Paris 06, Inserm, CNRS, Institut du Cerveau et de la Moelle Épinière (ICM), Département de Neurologie, Institut de la Mémoire et de la Maladie d'Alzheimer (IM2A), Hôpital Pitié-Salpêtrière, Paris, France.
24
Banner Alzheimer's Institute, Phoenix, AZ, USA.
25
University of Pittsburgh School of Medicine, Department of Psychiatry, Pittsburgh, PA, USA.
26
Department of Nuclear Medicine, Technische Universitaet München, Munich, Germany.
27
Danish Dementia Research Center, Department of Neurology, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark.
28
Department of Geriatrics, Karolinska University Hospital Huddinge, Section of Clinical Geriatrics, Institution of NVS, Karolinska Institutet, Stockholm, Sweden.
29
Third Department of Neurology, Aristotle University of Thessaloniki, Thessaloniki, Greece.
30
Department of Psychiatry and Psychotherapy, Klinikum rechts der Isar der Technischen Universitaet München, Munich, Germany.
31
AXA Research Fund & UPMC Chair, Sorbonne Universités, Université Pierre et Marie Curie (UPMC) Paris 06, Inserm, CNRS, Institut du Cerveau et de la Moelle Épinière (ICM), Département de Neurologie, Institut de la Mémoire et de la Maladie d'Alzheimer (IM2A), Hôpital Pitié-Salpêtrière, Paris, France; Department of Psychiatry, Alzheimer Memorial Center and Geriatric Psychiatry Branch, Ludwig-Maximilian University, Munich, Germany.
32
Department of Neurology, University of Eastern Finland and Kuopio University Hospital, Kuopio, Finland.
33
Memory Clinic, Danish Dementia Research Center, Rigshospitalet, Copenhagen, Denmark.
34
Department of Imaging and Pathology, Catholic University Leuven, Leuven, Belgium.
35
School of Medicine, Center for Brain Health, New York University, New York, NY, USA.
36
Department of Psychiatry and Psychotherapy, University of Bonn, German Center for Neurodegenerative Diseases (DZNE), Bonn, Germany.
37
Geriatric Medicine, Department of Clinical and Experimental Medicine, University of Linköping, Linköping, Sweden.
38
Department of Geriatric Medicine, Radboud Alzheimer Center, Radboud University Medical Center, Nijmegen, the Netherlands.
39
Knight Alzheimer's Disease Research Center, Department of Neurology, Washington University School of Medicine, St Louis, MO, USA.
40
Department of Neurodegeneration Diagnostics, Leading National Research Centre in Białystok (KNOW), Medical University of Białystok, Białystok, Poland.
41
Department of Neurology, Postgraduate Institute of Medical Education and Research (PGIMER), Chandigarh, India.
42
Department of Psychiatry and Psychotherapy, Charité Berlin, German Center for Neurodegenerative Diseases (DZNE), Berlin, Germany.
43
Neurology Service, Universitary Hospital Marqués de Valdecilla, CIBERNED, IDIVAL, Santander, Spain.
44
Department of Psychiatry and Psychotherapy, University Medical Center, Georg-August University, Göttingen, Germany.
45
Sektion Gerontopsychiatrie, Universität Heidelberg, Heidelberg, Germany.
46
Department of Neurology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea.
47
Department of Geriatrics-Gerontology-Gerontopsychiatry, Carol Davila University of Medicine and Pharmacy, Bucharest, Romania.
48
Clinical Memory Research Unit, Clinical Sciences Malmö, Lund University, Lund, Sweden.
49
Neurochemistry Laboratory and Biobank, Department of Clinical Chemistry, Amsterdam Neuroscience, VU University Medical Center, Amsterdam, the Netherlands.
50
Department of Neurology, Donders Institute for Brain, Cognition and Behaviour, Radboud Alzheimer Center, Radboud University Medical Center, Nijmegen, the Netherlands; Department of Laboratory Medicine, Donders Institute for Brain, Cognition and Behaviour, Radboud Alzheimer Center, Radboud University Medical Center, Nijmegen, the Netherlands.
51
Department of Psychiatry and Psychotherapy, University Medical Center, Georg-August University, Göttingen, Germany; Department of Psychiatry and Psychotherapy, University Medical Center, Georg-August University, Göttingen, Germany.
52
Laboratory for Cognitive Neurology and Alzheimer Research Centre KU Leuven, Catholic University Leuven, Leuven, Belgium.
53
Division of Neuroscience, Medical Research Council Clinical Sciences Centre, Imperial College London, London, UK.
54
Department of Nuclear Medicine, University of Cologne, Cologne, Germany.
55
Neurologie de la Mémoire et du Langage, Centre Hospitalier Sainte-Anne, Université Paris Descartes, Sorbonne Paris Cité, Paris, France.
56
Department of Neurology, University of Pennsylvania, Philadelphia, PA, USA.
57
Banner Alzheimer's Institute, Phoenix, AZ, USA; Eli Lilly, Indianapolis, IN, USA; Department of Neurosciences, University of California, San Diego, CA, USA.
58
Department of Neuropsychiatry, Seoul National University, College of Medicine, Seoul, South Korea.
59
Department NVS, Center for Alzheimer Research, Translational Alzheimer Neurobiology, Karolinska Institutet and Geriatric Medicine, Karolinska University Hospital, Stockholm, Sweden.
60
CHRU de Tours, CIC INSERM 1415, INSERM U930, Université François Rabelais de Tours, Tours, France.
61
Turku PET Centre and Division of Clinical Neurosciences Turku, University of Turku and Turku University Hospital, Turku, Finland.
62
Department of Molecular Neuroscience, UCL Institute of Neurology, Queen Square, London, UK; UK Dementia Research Institute, London, UK; Institute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry, The Sahlgrenska Academy at University of Gothenburg, Mölndal, Sweden; Sweden and Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital, Mölndal, Sweden.
63
Institute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry, The Sahlgrenska Academy at University of Gothenburg, Mölndal, Sweden; Sweden and Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital, Mölndal, Sweden.
64
Department of Neurology, Memory and Aging Center, University of California, San Francisco, CA, USA.
65
Department of Radiology and Nuclear Medicine, VU University Medical Center, Neuroscience Campus Amsterdam, Amsterdam, the Netherlands.
66
Department of Neurology and Alzheimer Center, VU University Medical Center, Neuroscience Campus Amsterdam, Amsterdam, the Netherlands; Department of Epidemiology and Biostatistics, VU University Medical Center, Amsterdam, the Netherlands.
67
Department of Neurology and Alzheimer Center, VU University Medical Center, Neuroscience Campus Amsterdam, Amsterdam, the Netherlands; Department of Psychiatry and Neuropsychology, School for Mental Health and Neuroscience, Alzheimer Center Limburg, Maastricht University, Maastricht, the Netherlands.
68
Clinical Memory Research Unit, Clinical Sciences Malmö, Lund University, Lund, Sweden; Department of Neurology and Alzheimer Center, VU University Medical Center, Neuroscience Campus Amsterdam, Amsterdam, the Netherlands; Department of Radiology and Nuclear Medicine, VU University Medical Center, Neuroscience Campus Amsterdam, Amsterdam, the Netherlands. Electronic address: r.ossenkoppele@vumc.nl.

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

PMID:
29601787
DOI:
10.1016/j.jalz.2018.02.009
[Indexed for MEDLINE]

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