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Hum Mol Genet. 2014 Dec 15;23(24):6644-58. doi: 10.1093/hmg/ddu372. Epub 2014 Jul 15.

SUCLG2 identified as both a determinator of CSF Aβ1-42 levels and an attenuator of cognitive decline in Alzheimer's disease.

Author information

1
Department of Psychiatry and Psychotherapy, Institute of Human Genetics, alfredo.ramirez@ukb.uni-bonn.de.
2
Department of Neurology and Alzheimer Center, Neuroscience Campus Amsterdam, VU University Medical Center, 1081 HZ, Amsterdam, The Netherlands, Department of Epidemiology & Biostatistics, VU University Medical Center, 1007 MB, Amsterdam, The Netherlands.
3
German Center for Neurodegenerative Diseases (DZNE), 53175, Bonn, Germany.
4
Clinical Neuroscience Unit, Department of Neurology.
5
Institute of Human Genetics, Department of Genomics, Life & Brain Center.
6
Department of Psychiatry and Psychotherapy, Universitätsklinikum Erlangen, and Friedrich-Alexander Universität Erlangen-Nürnberg, 91054, Erlangen, Germany.
7
Department of Psychiatry and Psychotherapy.
8
Clinical Neuroscience Unit, Department of Neurology, German Center for Neurodegenerative Diseases (DZNE), 53175, Bonn, Germany.
9
Department of Psychiatry, Hope Center for Neurological Disorders, School of Medicine.
10
Institute of Human Genetics, Department of Genomics, Life & Brain Center, Division of Medical Genetics, University Hospital and Department of Biomedicine, University of Basel, CH-4058, Basel, Switzerland.
11
Department of Psychiatry, Charité, 14050, Berlin, Germany.
12
Center for Clinical Epidemiology & Biostatistics, University of Pennsylvania, PA 19104, Philadelphia, USA.
13
Department of Neurology, Boston University School of Medicine, MA 02118, Boston, USA, The Framingham Heart Study, MA 01702, Framingham, USA.
14
Inserm, U744, Lille 59000, France, Université Lille 2, Lille 59000, France, Institut Pasteur de Lille, Lille 59000, France.
15
Institute of Psychological Medicine and Clinical Neurosciences, MRC Centre for Neuropsychiatric Genetics & Genomics, Cardiff University, Cardiff, UK.
16
Department of Geriatric Psychiatry, Central Institute of Mental Health, Medical Faculty Mannheim, University of Heidelberg, 68159, Mannheim, Germany.
17
Centre for Geriatric Medicine and Section of Gerontopsychiatry and Neuropsychology, Medical School, University of Freiburg, 79106, Freiburg, Germany.
18
Department of Fundamental Neurosciences, UNIL, 1005 Lausanne, Switzerland and.
19
Department of Psychiatry and Psychotherapy, University of Göttingen, 37075 Göttingen, Germany.
20
Department of Psychiatry, Department of Genetics, Washington University, St. Louis, MO 63110, USA.
21
Department of Psychiatry and Psychotherapy, German Center for Neurodegenerative Diseases (DZNE), 53175, Bonn, Germany.
22
Institute for Medical Biometry, Informatics, and Epidemiology, University of Bonn, 53127, Bonn, Germany, German Center for Neurodegenerative Diseases (DZNE), 53175, Bonn, Germany.

Abstract

Cerebrospinal fluid amyloid-beta 1-42 (Aβ1-42) and phosphorylated Tau at position 181 (pTau181) are biomarkers of Alzheimer's disease (AD). We performed an analysis and meta-analysis of genome-wide association study data on Aβ1-42 and pTau181 in AD dementia patients followed by independent replication. An association was found between Aβ1-42 level and a single-nucleotide polymorphism in SUCLG2 (rs62256378) (P = 2.5×10(-12)). An interaction between APOE genotype and rs62256378 was detected (P = 9.5 × 10(-5)), with the strongest effect being observed in APOE-ε4 noncarriers. Clinically, rs62256378 was associated with rate of cognitive decline in AD dementia patients (P = 3.1 × 10(-3)). Functional microglia experiments showed that SUCLG2 was involved in clearance of Aβ1-42.

PMID:
25027320
PMCID:
PMC4240204
DOI:
10.1093/hmg/ddu372
[Indexed for MEDLINE]
Free PMC Article

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