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Brain region–specific lipid alterations in the PLB4 hBACE1 knock-in mouse model of Alzheimer’s disease

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Dey_2020_LHD_Region_specific_CC.pdf (3.378Mb)
Date
31/08/2020
Author
Dey, Madhurima
Gunn-Moore, Frank J.
Platt, Bettina
Smith, Terry K.
Keywords
PLB4
Quantitative lipidomics
Brain regions
RC0321 Neuroscience. Biological psychiatry. Neuropsychiatry
DAS
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Abstract
Background Lipid dysregulation is associated with several key characteristics of Alzheimer’s disease (AD), including amyloid-β and tau neuropathology, neurodegeneration, glucose hypometabolism, as well as synaptic and mitochondrial dysfunction. The β-site amyloid precursor protein cleavage enzyme 1 (BACE1) is associated with increased amyloidogenesis, and has been affiliated with diabetes via its role in metabolic regulation. Methods The research presented herein investigates the role of hBACE1 in lipid metabolism and whether specific brain regions show increased vulnerability to lipid dysregulation. By utilising advanced mass spectrometry techniques, a comprehensive, quantitative lipidomics analysis was performed to investigate the phospholipid, sterol, and fatty acid profiles of the brain from the well-known PLB4 hBACE1 knock-in mouse model of AD, which also shows a diabetic phenotype, to provide insight into regional alterations in lipid metabolism. Results Results show extensive region – specific lipid alterations in the PLB4 brain compared to the wild-type, with decreases in the phosphatidylethanolamine content of the cortex and triacylglycerol content of the hippocampus and hypothalamus, but increases in the phosphatidylcholine, phosphatidylinositol, and diacylglycerol content of the hippocampus. Several sterol and fatty acids were also specifically decreased in the PLB4 hippocampus. Conclusion Collectively, the lipid alterations observed in the PLB4 hBACE1 knock-in AD mouse model highlights the regional vulnerability of the brain, in particular the hippocampus and hypothalamus, to lipid dysregulation, hence supports the premise that metabolic abnormalities have a central role in both AD and diabetes.
Citation
Dey , M , Gunn-Moore , F J , Platt , B & Smith , T K 2020 , ' Brain region–specific lipid alterations in the PLB4 hBACE1 knock-in mouse model of Alzheimer’s disease ' , Lipids in Health and Disease , vol. 19 , 201 . https://doi.org/10.1186/s12944-020-01367-8
Publication
Lipids in Health and Disease
Status
Peer reviewed
DOI
https://doi.org/10.1186/s12944-020-01367-8
ISSN
1476-511X
Type
Journal article
Rights
Copyright © The Author(s). 2020 Open Access. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.
Description
Authors thank the Alzheimer’s Society Scottish Doctoral Training Centre and the RS Macdonald Trust Transition Fund for funding the research presented.
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  • University of St Andrews Research
URI
http://hdl.handle.net/10023/20584

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