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

被引：48

作者：

Morgen, Katrin ^{[1
]}

Ramirez, Alfredo ^{[2
,3
]}

Froelich, Lutz ^{[1
]}

Tost, Heike ^{[1
]}

Plichta, Michael M. ^{[1
]}

Koelsch, Heike ^{[3
]}

Rakebrandt, Fabian ^{[4
]}

Rienhoff, Otto ^{[4
]}

Jessen, Frank ^{[2
]}

Peters, Oliver ^{[5
]}

Jahn, Holger ^{[6
]}

Luckhaus, Christian ^{[7
]}

Huell, Michael ^{[8
]}

Gertz, Hermann-Josef ^{[9
]}

Schroeder, Johannes ^{[10
]}

Hampel, Harald ^{[11
]}

Teipel, Stefan J. ^{[12
,13
]}

Pantel, Johannes ^{[14
]}

Heuser, Isabella ^{[3
]}

Wiltfang, Jens ^{[15
]}

Ruether, Eckart ^{[16
]}

Kornhuber, Johannes ^{[17
]}

Maier, Wolfgang ^{[2
,18
]}

Meyer-Lindenberg, Andreas ^{[1
]}

机构：

[1] Heidelberg Univ, Med Fac Mannheim, Cent Inst Mental Hlth, Heidelberg, Germany

[2] Univ Bonn, Dept Psychiat & Psychotherapy, Bonn, Germany

[3] Univ Bonn, Inst Human Genet, Bonn, Germany

[4] Univ Gottingen, Dept Med Informat, D-37073 Gottingen, Germany

[5] Charite, Dept Psychiat & Psychotherapy, Berlin, Germany

[6] Univ Hamburg, Dept Psychiat & Psychotherapy, Hamburg, Germany

[7] Univ Dusseldorf, Dept Psychiat & Psychotherapy, Dusseldorf, Germany

[8] Univ Freiburg, Dept Psychiat & Psychotherapy, D-79106 Freiburg, Germany

[9] Univ Leipzig, Dept Psychiat & Psychotherapy, D-04109 Leipzig, Germany

[10] Heidelberg Univ, Dept Psychiat & Psychotherapy, Heidelberg, Germany

[11] Univ Paris 06, Hop Salpetriere Pris, Dept Neurol, Inst Memoire & Malad Alzheimer, F-75252 Paris 05, France

[12] Univ Rostock, Dept Psychiat & Psychotherapy, D-18055 Rostock, Germany

[13] German Ctr Neurodegenerat Dis DZNE, Rostock, Germany

[14] Goethe Univ Frankfurt, Inst Gen Practice, D-60054 Frankfurt, Germany

[15] Univ Essen Gesamthsch, Dept Psychiat & Psychotherapy, Essen, Germany

[16] Univ Gottingen, Dept Psychiat & Psychotherapy, D-37073 Gottingen, Germany

[17] Univ Erlangen Nurnberg, D-91054 Erlangen, Germany

[18] German Ctr Neurodegenerat Dis, Bonn, Germany

来源：

ALZHEIMERS & DEMENTIA | 2014年 / 10卷 / 05期

关键词：

Alzheimer's disease; PICALM; APOE; Genetic interaction; Brain atrophy; AMYLOID PRECURSOR PROTEIN; APOLIPOPROTEIN-E; A-BETA; DIAGNOSIS; CLATHRIN; ENDOCYTOSIS; DEMENTIA; CALM; CLU; PATHOGENESIS;

D O I：

10.1016/j.jalz.2013.11.001

中图分类号：

R74 [神经病学与精神病学];

学科分类号：

摘要：

Background: Evidence has emerged indicating that the epsilon 4 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 epsilon 4 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 epsilon 4 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 epsilon 4 carriers. (C) 2014 The Alzheimer's Association. All rights reserved.

引用

页码：S269 / S276

页数：8

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