Relationships Between Plasma Lipids Species, Gender, Risk Factors, and Alzheimer's Disease.
APOEɛ4
Aging
Alzheimer’s disease
gender
lipid
species
Journal
Journal of Alzheimer's disease : JAD
ISSN: 1875-8908
Titre abrégé: J Alzheimers Dis
Pays: Netherlands
ID NLM: 9814863
Informations de publication
Date de publication:
2020
2020
Historique:
pubmed:
1
6
2020
medline:
8
5
2021
entrez:
1
6
2020
Statut:
ppublish
Résumé
Lipid metabolism is altered in Alzheimer's disease (AD); however, the relationship between AD risk factors (age, APOEɛ4, and gender) and lipid metabolism is not well defined. We investigated whether altered lipid metabolism associated with increased age, gender, and APOE status may contribute to the development of AD by examining these risk factors in healthy controls and also clinically diagnosed AD individuals. We performed plasma lipidomic profiling (582 lipid species) of the Australian Imaging, Biomarkers and Lifestyle flagship study of aging cohort (AIBL) using liquid chromatography-mass spectrometry. Linear regression and interaction analysis were used to explore the relationship between risk factors and plasma lipid species. We observed strong associations between plasma lipid species with gender and increasing age in cognitively normal individuals. However, APOEɛ4 was relatively weakly associated with plasma lipid species. Interaction analysis identified differential associations of sphingolipids and polyunsaturated fatty acid esterified lipid species with AD based on age and gender, respectively. These data indicate that the risk associated with age, gender, and APOEɛ4 may, in part, be mediated by changes in lipid metabolism. This study extends our existing knowledge of the relationship between the lipidome and AD and highlights the complexity of the relationships between lipid metabolism and AD at different ages and between men and women. This has important implications for how we assess AD risk and also for potential therapeutic strategies involving modulation of lipid metabolic pathways.
Sections du résumé
BACKGROUND
Lipid metabolism is altered in Alzheimer's disease (AD); however, the relationship between AD risk factors (age, APOEɛ4, and gender) and lipid metabolism is not well defined.
OBJECTIVE
We investigated whether altered lipid metabolism associated with increased age, gender, and APOE status may contribute to the development of AD by examining these risk factors in healthy controls and also clinically diagnosed AD individuals.
METHODS
We performed plasma lipidomic profiling (582 lipid species) of the Australian Imaging, Biomarkers and Lifestyle flagship study of aging cohort (AIBL) using liquid chromatography-mass spectrometry. Linear regression and interaction analysis were used to explore the relationship between risk factors and plasma lipid species.
RESULTS
We observed strong associations between plasma lipid species with gender and increasing age in cognitively normal individuals. However, APOEɛ4 was relatively weakly associated with plasma lipid species. Interaction analysis identified differential associations of sphingolipids and polyunsaturated fatty acid esterified lipid species with AD based on age and gender, respectively. These data indicate that the risk associated with age, gender, and APOEɛ4 may, in part, be mediated by changes in lipid metabolism.
CONCLUSION
This study extends our existing knowledge of the relationship between the lipidome and AD and highlights the complexity of the relationships between lipid metabolism and AD at different ages and between men and women. This has important implications for how we assess AD risk and also for potential therapeutic strategies involving modulation of lipid metabolic pathways.
Identifiants
pubmed: 32474467
pii: JAD191304
doi: 10.3233/JAD-191304
pmc: PMC7369125
doi:
Substances chimiques
Apolipoprotein E4
0
Biomarkers
0
Lipids
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
303-315Références
FEBS Lett. 2017 Sep;591(18):2761-2788
pubmed: 28796901
Br J Nutr. 2002 Oct;88(4):355-63
pubmed: 12323085
Dialogues Clin Neurosci. 2016 Dec;18(4):437-446
pubmed: 28179815
Science. 1993 Aug 13;261(5123):921-3
pubmed: 8346443
J Lipid Res. 2005 May;46(5):839-61
pubmed: 15722563
Arch Neurol. 2003 Jul;60(7):940-6
pubmed: 12873849
J Alzheimers Dis. 2015;50(3):887-94
pubmed: 26836186
J Chromatogr A. 2011 Oct 21;1218(42):7713-22
pubmed: 21872257
PLoS One. 2017 Jul 3;12(7):e0180675
pubmed: 28672041
Lipids. 2015 Sep;50(9):861-72
pubmed: 26001986
Neurology. 2013 May 7;80(19):1778-83
pubmed: 23390181
Proc Natl Acad Sci U S A. 2003 Sep 30;100(20):11735-40
pubmed: 14504402
Stat Med. 2011 Feb 20;30(4):377-99
pubmed: 21225900
J Neurochem. 2001 May;77(4):1168-80
pubmed: 11359882
Biochim Biophys Acta. 2010 Aug;1801(8):860-7
pubmed: 20303415
J Lipid Res. 2013 Jun;54(6):1523-30
pubmed: 23549332
J Neurochem. 2011 Mar;116(5):916-25
pubmed: 21214572
J Lipid Res. 2013 Oct;54(10):2898-908
pubmed: 23868910
Neurology. 2010 Sep 7;75(10):889-97
pubmed: 20820000
ScientificWorldJournal. 2012;2012:141240
pubmed: 22547976
Biochem J. 1999 Mar 15;338 ( Pt 3):769-76
pubmed: 10051451
Br J Nutr. 2002 Oct;88(4):411-20
pubmed: 12323090
Dement Geriatr Cogn Disord. 2010;30(2):147-54
pubmed: 20733307
Nat Neurosci. 2008 Nov;11(11):1311-8
pubmed: 18931664
Neurology. 2001 Mar 13;56(5):650-4
pubmed: 11245718
Neurology. 1999 Dec 10;53(9):1992-7
pubmed: 10599770
Arch Neurol. 1996 Oct;53(10):1056-61
pubmed: 8859068
Neurology. 1994 Jul;44(7):1215-20
pubmed: 8035918
J Lipid Res. 2007 Nov;48(11):2485-98
pubmed: 17664527
J Neuropathol Exp Neurol. 1999 Jul;58(7):740-7
pubmed: 10411344
Metabolites. 2015 Jun 17;5(2):389-403
pubmed: 26090945
Cell Mol Biol (Noisy-le-grand). 2003 Jul;49(5):809-18
pubmed: 14528918
Reprod Nutr Dev. 2005 Sep-Oct;45(5):581-97
pubmed: 16188209
J Cell Biol. 2003 Jan 6;160(1):113-23
pubmed: 12515826
Cell Chem Biol. 2019 Jan 17;26(1):71-84.e4
pubmed: 30415965
Compr Psychiatry. 2015 Oct;62:114-22
pubmed: 26343475
Int Psychogeriatr. 2009 Aug;21(4):672-87
pubmed: 19470201
Biochim Biophys Acta. 2010 Aug;1801(8):784-90
pubmed: 20553961