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Alzheimers Dement. 2014 Oct;10(5 Suppl):S269-76. doi: 10.1016/j.jalz.2013.11.001. Epub 2014 Mar 6.

Genetic interaction of PICALM and APOE is associated with brain atrophy and cognitive impairment in Alzheimer's disease.

Author information

1
Central Institute of Mental Health, Medical Faculty Mannheim/Heidelberg University, Heidelberg, Germany. Electronic address: katrin.morgen@zi-mannheim.de.
2
Department of Psychiatry and Psychotherapy, University of Bonn, Bonn, Germany; Institute of Human Genetics, University of Bonn, Bonn, Germany.
3
Central Institute of Mental Health, Medical Faculty Mannheim/Heidelberg University, Heidelberg, Germany.
4
Institute of Human Genetics, University of Bonn, Bonn, Germany.
5
Department of Medical Informatics, University of Göttingen, Göttingen, Germany.
6
Department of Psychiatry and Psychotherapy, University of Bonn, Bonn, Germany; Friedrich Alexander University of Erlangen-Nuremberg, Erlangen, Germany.
7
Department of Psychiatry and Psychotherapy, Charité Berlin, Berlin, Germany.
8
Department of Psychiatry and Psychotherapy, University of Hamburg, Hamburg, Germany.
9
Department of Psychiatry and Psychotherapy, University of Düsseldorf, Düsseldorf, Germany.
10
Department of Psychiatry and Psychotherapy, University of Freiburg, Freiburg, Germany.
11
Department of Psychiatry and Psychotherapy, University of Leipzig, Leipzig, Germany.
12
Department of Psychiatry and Psychotherapy, University of Heidelberg, Heidelberg, Germany.
13
Département de Neurologie Institut de la Mémoire et de la Maladie d'Alzheimer, Université Pierre et Marie Curie, Hôpital de la Salpétriére Paris, France.
14
Department of Psychiatry and Psychotherapy, University of Rostock, Rostock, Germany; German Center for Neurodegenerative Diseases (DZNE), Rostock, Germany.
15
Institute of General Practice, University of Frankfurt, Frankfurt, Germany.
16
Department of Psychiatry and Psychotherapy, University of Essen, Essen, Germany.
17
Department of Psychiatry and Psychotherapy, University of Göttingen, Göttingen, Germany.
18
Friedrich Alexander University of Erlangen-Nuremberg, Erlangen, Germany.
19
Department of Psychiatry and Psychotherapy, University of Bonn, Bonn, Germany; German Center for Neurodegenerative Diseases, Bonn, Germany.

Abstract

BACKGROUND:

Evidence has emerged indicating that the ε4 allele of APOE and PICALM interact in conferring risk of Alzheimer's disease (AD). The biologic basis of this interaction is unclear, but it is likely to have phenotypic relevance and contribute to the structural and clinical heterogeneity of AD.

METHODS:

The aim of this study was to investigate interaction effects of the APOE ε4 allele and the alleles at the single-nucleotide polymorphism rs3851179 located in the PICALM locus. We analyzed brain volumes and cognitive phenotypes of 165 patients with early AD dementia.

RESULTS:

There was a synergistic adverse effect of homozygosity for the PICALM risk allele G in rs3851179 and APOE ε4 on volume in prefrontal and performance on the Trail Making Test A, which is sensitive to processing speed and working memory function.

CONCLUSIONS:

The data suggest a neural mechanism for APOE-PICALM interactions in patients with manifest AD and indicate that the PICALM genotype modulates both brain atrophy and cognitive performance in APOE ε4 carriers.

KEYWORDS:

APOE; Alzheimer's disease; Brain atrophy; Genetic interaction; PICALM

PMID:
24613704
DOI:
10.1016/j.jalz.2013.11.001
[Indexed for MEDLINE]

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