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Sequence variants of IDE are associated with the extent of β-amyloid deposition in the Alzheimer's disease brain

Wilcock, Gordon K.; Blomqvist, Mia E.L.; Cairns, Nigel J.; Feuk, Lars; Brookes, Anthony J.; Love, Seth; Blennow, Kaj; Kehoe, Patrick G.; Prince, Jonathan A.; Chalmers, Katy; Andreasen, Niels; Bogdanovic, Nenad

Authors

Gordon K. Wilcock

Mia E.L. Blomqvist

Nigel J. Cairns

Lars Feuk

Anthony J. Brookes

Seth Love

Kaj Blennow

Patrick G. Kehoe

Jonathan A. Prince

Katy Chalmers

Niels Andreasen

Nenad Bogdanovic



Abstract

Insulin degrading enzyme, encoded by IDE, plays a primary role in the degradation of amyloid β-protein (Aβ), the deposition of which in senile plaques is one of the defining hallmarks of Alzheimer's disease (AD). We recently identified haplotypes in a broad linkage disequilibrium (LD) block encompassing IDE that associate with several AD-related quantitative traits. Here, by examining 32 polymorphic markers extending across IDE and testing quantitative measures of plaque density and cognitive function in three independent Swedish AD samples, we have refined the probable position of pathogenic sequences to a 3′ region of IDE, with local maximum effects in the proximity of marker rs1887922. To replicate these findings, a subset of variants were examined against measures of brain Aβ load in an independent English AD sample, whereby maximum effects were again observed for rs1887922. For both Swedish and English autopsy materials, variation at rs1887922 explained approximately 10% of the total variance in the respective histopathology traits. However, across all clinical materials studied to date, this variant site does not appear to associate directly with disease, suggesting that IDE may affect AD severity rather than risk. Results indicate that alleles of IDE contribute to variability in Aβ deposition in the AD brain and suggest that this relationship may have relevance for the degree of cognitive dysfunction in AD patients. © 2004 Elsevier Inc. All rights reserved.

Citation

Prince, J. A., Kehoe, P. G., Blennow, K., Love, S., Brookes, A. J., Feuk, L., …Wilcock, G. (2005). Sequence variants of IDE are associated with the extent of β-amyloid deposition in the Alzheimer's disease brain. Neurobiology of Aging, 26(6), 795-802. https://doi.org/10.1016/j.neurobiolaging.2004.07.011

Journal Article Type Article
Publication Date Jan 1, 2005
Journal Neurobiology of Aging
Print ISSN 0197-4580
Publisher Elsevier
Peer Reviewed Not Peer Reviewed
Volume 26
Issue 6
Pages 795-802
DOI https://doi.org/10.1016/j.neurobiolaging.2004.07.011
Keywords IDE, linkage disequilibrium, Alzheimer's disease, β-Amyloid
Public URL https://uwe-repository.worktribe.com/output/1049357
Publisher URL http://dx.doi.org/10.1016/j.neurobiolaging.2004.07.011




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