Universität zu Köln

Ahmad, Shahzad ORCID: 0000-0002-8658-3790, Bannister, Christian, van der Lee, Sven J., Vojinovic, Dina ORCID: 0000-0001-5744-0232, Adams, Hieab H. H., Ramirez, Alfredo ORCID: 0000-0003-4991-763X, Escott-Price, Valentina, Sims, Rebecca, Baker, Emily, Williams, Julie ORCID: 0000-0002-4069-0259, Holmans, Peter, Vernooij, Meike W., Ikram, M. Arfan, Amin, Najaf and van Duijn, Cornelia M. (2018). Disentangling the biological pathways involved in early features of Alzheimer's disease in the Rotterdam Study. Alzheimers. Dement., 14 (7). S. 848 - 858. NEW YORK: ELSEVIER SCIENCE INC. ISSN 1552-5279

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Abstract

Introduction: Exploring the role of Alzheimer's disease (AD) implicated pathways in the predementia phase may provide new insight for preventive and clinical trials targeting disease specific pathways. Methods: We constructed weighted Genetic risk scores, first based on 20 genome-wide significant AD risk variants and second clustering these variants within pathways. Risk scores were investigated for their association with AD, mild cognitive impairment, and brain magnetic resonance imaging phenotypes including white matter lesions, hippocampal volume, and brain volume. Results: The risk score capturing endocytosis pathway was significantly associated with mild cognitive impairment (P = 1.44 x 10(-4)). Immune response (P = .016) and clathrin/AP2 adaptor complex pathway (P = 3.55x 10(-3)) excluding apolipoprotein E also showed modest association with white matter lesions but did not sustain Bonferroni correction (P = 9.09 x 10(-4)). Discussion: Our study suggests that the clinical spectrum of early AD pathology is explained by different biological pathways, in particular, the endocytosis, clathrin/AP2 adaptor complex, and immune response pathways, that are independent of apolipoprotein E (APOE). (C) 2018 The Authors. Published by Elsevier Inc. on behalf of the Alzheimer's Association. This is an open access article under the CC BY-NC-ND license.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Ahmad, Shahzad UNSPECIFIED orcid.org/0000-0002-8658-3790 UNSPECIFIED Bannister, Christian UNSPECIFIED UNSPECIFIED UNSPECIFIED van der Lee, Sven J. UNSPECIFIED UNSPECIFIED UNSPECIFIED Vojinovic, Dina UNSPECIFIED orcid.org/0000-0001-5744-0232 UNSPECIFIED Adams, Hieab H. H. UNSPECIFIED UNSPECIFIED UNSPECIFIED Ramirez, Alfredo UNSPECIFIED orcid.org/0000-0003-4991-763X UNSPECIFIED Escott-Price, Valentina UNSPECIFIED UNSPECIFIED UNSPECIFIED Sims, Rebecca UNSPECIFIED UNSPECIFIED UNSPECIFIED Baker, Emily UNSPECIFIED UNSPECIFIED UNSPECIFIED Williams, Julie UNSPECIFIED orcid.org/0000-0002-4069-0259 UNSPECIFIED Holmans, Peter UNSPECIFIED UNSPECIFIED UNSPECIFIED Vernooij, Meike W. UNSPECIFIED UNSPECIFIED UNSPECIFIED Ikram, M. Arfan UNSPECIFIED UNSPECIFIED UNSPECIFIED Amin, Najaf UNSPECIFIED UNSPECIFIED UNSPECIFIED van Duijn, Cornelia M. UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-180192
DOI:	10.1016/j.jalz.2018.01.005
Journal or Publication Title:	Alzheimers. Dement.
Volume:	14
Number:	7
Page Range:	S. 848 - 858
Date:	2018
Publisher:	ELSEVIER SCIENCE INC
Place of Publication:	NEW YORK
ISSN:	1552-5279
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language MILD COGNITIVE IMPAIRMENT; WHITE-MATTER HYPERINTENSITIES; BRAIN-TISSUE SEGMENTATION; GENOME-WIDE ASSOCIATION; COMMON VARIANTS; GENETIC RISK; GENOTYPE IMPUTATION; CEREBROSPINAL-FLUID; APOLIPOPROTEIN-E; DOWN-SYNDROME Multiple languages Clinical Neurology Multiple languages
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/18019