Universität zu Köln

Grimmer, Timo, Goldhardt, Oliver, Guo, Liang-Hao, Yousefi, Behrooz H., Foerster, Stefan, Drzezga, Alexander, Sorg, Christian, Alexopoulos, Panagiotis, Foerstl, Hans, Kurz, Alexander and Perneczky, Robert ORCID: 0000-0003-1981-7435 (2014). LRP-1 polymorphism is associated with global and regional amyloid load in Alzheimer's disease in humans in-vivo. NeuroImage-Clin., 4. S. 411 - 417. OXFORD: ELSEVIER SCI LTD. ISSN 2213-1582

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Abstract

Objective: Impaired amyloid clearance has been proposed to contribute to beta-amyloid deposition in sporadic late-onset Alzheimer's disease (AD). Low density lipoprotein receptor-related protein 1 (LRP-1) is involved in the active outward transport of beta-amyloid across the blood-brain barrier (BBB). The C667T polymorphism (rs1799986) of the LRP-1 gene has been inconsistently associated with AD in genetic studies. We aimed to elucidate the association of this polymorphism with in-vivo brain amyloid load of AD patients using amyloid PET with [C-11] PiB. Materials and methods: 72 patients with very mild to moderate AD were examined with amyloid PET and C667T polymorphism was obtained using TaqMan PCR assays. The association of C667T polymorphism with global and regional amyloid load was calculated using linear regression and voxel based analysis, respectively. The effect of the previously identified modulator of amyloid uptake, the apolipoprotein E genotype, on this association was also determined. Results: The regression analysis between amyloid load and C667T polymorphism was statistically significant (p = 0.046, beta = 0.236). In an additional analysis ApoE genotype and gender were identified to explain further variability of amyloid load. Voxel based analysis revealed a significant (p < 0.05) association between C667T polymorphism and amyloid uptake in the temporo-parietal cortex bilaterally. ApoE did not interact significantly with the LRP-1 polymorphism. Discussion: In conclusion, C667T polymorphism of LRP-1 is moderately but significantly associated with global and regional amyloid deposition in AD. The relationship appears to be independent of the ApoE genotype. This finding is compatible with the hypothesis that impaired amyloid clearance contributes to amyloid deposition in late-onset sporadic AD. (C) 2014 The Authors. Published by Elsevier Inc.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Grimmer, Timo UNSPECIFIED UNSPECIFIED UNSPECIFIED Goldhardt, Oliver UNSPECIFIED UNSPECIFIED UNSPECIFIED Guo, Liang-Hao UNSPECIFIED UNSPECIFIED UNSPECIFIED Yousefi, Behrooz H. UNSPECIFIED UNSPECIFIED UNSPECIFIED Foerster, Stefan UNSPECIFIED UNSPECIFIED UNSPECIFIED Drzezga, Alexander UNSPECIFIED UNSPECIFIED UNSPECIFIED Sorg, Christian UNSPECIFIED UNSPECIFIED UNSPECIFIED Alexopoulos, Panagiotis UNSPECIFIED UNSPECIFIED UNSPECIFIED Foerstl, Hans UNSPECIFIED UNSPECIFIED UNSPECIFIED Kurz, Alexander UNSPECIFIED UNSPECIFIED UNSPECIFIED Perneczky, Robert UNSPECIFIED orcid.org/0000-0003-1981-7435 UNSPECIFIED
URN:	urn:nbn:de:hbz:38-452606
DOI:	10.1016/j.nicl.2014.01.016
Journal or Publication Title:	NeuroImage-Clin.
Volume:	4
Page Range:	S. 411 - 417
Date:	2014
Publisher:	ELSEVIER SCI LTD
Place of Publication:	OXFORD
ISSN:	2213-1582
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language RECEPTOR-RELATED PROTEIN; BLOOD-BRAIN-BARRIER; INTERSTITIAL FLUID; BETA-PEPTIDE; A-BETA; GENETIC ASSOCIATION; CLINICAL-DIAGNOSIS; RAT-BRAIN; CLEARANCE; MECHANISM Multiple languages Neuroimaging Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/45260