Cholesterol and neurodegeneration: longitudinal changes in serum cholesterol biomarkers are associated with new lesions and gray matter atrophy in multiple sclerosis over 5 years of follow-up.
Adolescent
Adult
Aged
Apolipoprotein A-I
/ blood
Atrophy
Biomarkers
/ blood
Brain
/ diagnostic imaging
Cholesterol
/ blood
Cholesterol, HDL
/ blood
Cholesterol, LDL
/ blood
Female
Follow-Up Studies
Gray Matter
/ diagnostic imaging
Humans
Longitudinal Studies
Magnetic Resonance Imaging
Male
Middle Aged
Multiple Sclerosis
/ blood
Multiple Sclerosis, Relapsing-Remitting
/ blood
Neurodegenerative Diseases
/ blood
Neurologic Examination
Polymorphism, Single Nucleotide
Prospective Studies
Young Adult
HDL
atrophy
cholesterol
multiple sclerosis
neurodegeneration
progression
Journal
European journal of neurology
ISSN: 1468-1331
Titre abrégé: Eur J Neurol
Pays: England
ID NLM: 9506311
Informations de publication
Date de publication:
01 2020
01 2020
Historique:
received:
22
05
2019
accepted:
22
07
2019
pubmed:
2
8
2019
medline:
29
12
2020
entrez:
2
8
2019
Statut:
ppublish
Résumé
Cholesterol is an important structural component of myelin and essential for brain homeostasis. Our objective was to investigate whether longitudinal changes in cholesterol biomarkers are associated with neurodegeneration in multiple sclerosis (MS). This prospective, longitudinal study (n = 154) included 41 healthy controls, 76 relapsing-remitting MS subjects and 37 progressive MS subjects. Neurological examination, brain magnetic resonance imaging and blood samples were obtained at baseline and at 5-year follow-up visits. Cholesterol biomarkers measured included plasma total cholesterol, high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol and the apolipoproteins ApoA-I, Apo-II, ApoB, ApoC-II and ApoE. Key cholesterol pathway single nucleotide polymorphisms were genotyped. Greater percentage increases in HDL-C and ApoA-I levels were associated with a lower rate of gray matter and cortical volume loss. Greater percentage increases in low-density lipoprotein cholesterol were associated with increases in new T2 lesions. The percentage increases in HDL-C (P = 0.032) and ApoA-I (P = 0.007) were smaller in patients with relapsing-remitting MS at baseline who converted to secondary progressive MS during the 5-year follow-up period. Changes in HDL-C and ApoA-I were associated with lipoprotein lipase rs328 genotype status. Increases in HDL-C and ApoA-I have protective associations with magnetic resonance imaging measures of neurodegeneration in MS.
Sections du résumé
BACKGROUND AND PURPOSE
Cholesterol is an important structural component of myelin and essential for brain homeostasis. Our objective was to investigate whether longitudinal changes in cholesterol biomarkers are associated with neurodegeneration in multiple sclerosis (MS).
METHODS
This prospective, longitudinal study (n = 154) included 41 healthy controls, 76 relapsing-remitting MS subjects and 37 progressive MS subjects. Neurological examination, brain magnetic resonance imaging and blood samples were obtained at baseline and at 5-year follow-up visits. Cholesterol biomarkers measured included plasma total cholesterol, high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol and the apolipoproteins ApoA-I, Apo-II, ApoB, ApoC-II and ApoE. Key cholesterol pathway single nucleotide polymorphisms were genotyped.
RESULTS
Greater percentage increases in HDL-C and ApoA-I levels were associated with a lower rate of gray matter and cortical volume loss. Greater percentage increases in low-density lipoprotein cholesterol were associated with increases in new T2 lesions. The percentage increases in HDL-C (P = 0.032) and ApoA-I (P = 0.007) were smaller in patients with relapsing-remitting MS at baseline who converted to secondary progressive MS during the 5-year follow-up period. Changes in HDL-C and ApoA-I were associated with lipoprotein lipase rs328 genotype status.
CONCLUSIONS
Increases in HDL-C and ApoA-I have protective associations with magnetic resonance imaging measures of neurodegeneration in MS.
Substances chimiques
Apolipoprotein A-I
0
Biomarkers
0
Cholesterol, HDL
0
Cholesterol, LDL
0
Cholesterol
97C5T2UQ7J
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
188-e4Informations de copyright
© 2019 European Academy of Neurology.
Références
Browne RW, Weinstock-Guttman B, Horakova D, et al. Apolipoproteins are associated with new MRI lesions and deep grey matter atrophy in clinically isolated syndromes. J Neurol Neurosurg Psychiatry 2014; 85: 859-864.
Weinstock-Guttman B, Zivadinov R, Mahfooz N, et al. Serum lipid profiles are associated with disability and MRI outcomes in multiple sclerosis. J Neuroinflammation 2011; 8: 127.
Fellows K, Uher T, Browne RW, et al. Protective associations of HDL with blood-brain barrier injury in multiple sclerosis patients. J Lipid Res 2015; 56: 2010-2018.
Tettey P, Simpson S Jr, Taylor B, et al. An adverse lipid profile is associated with disability and progression in disability, in people with MS. Mult Scler 2014; 20:1737-744.
Zhornitsky S, McKay KA, Metz LM, Teunissen CE, Rangachari M. Cholesterol and markers of cholesterol turnover in multiple sclerosis: relationship with disease outcomes. Mult Scler Relat Disord 2016; 5: 53-65.
Kreisberg RA, Kasim S. Cholesterol metabolism and aging. Am J Med 1987; 82: 54-60.
Zhang Y, Zhou Y, van der Mei IAF, et al. Lipid-related genetic polymorphisms significantly modulate the association between lipids and disability progression in multiple sclerosis. J Neurol Neurosurg Psychiatry 2019; 1-6.
Lublin FD, Reingold SC, Cohen JA, et al. Defining the clinical course of multiple sclerosis: the 2013 revisions. Neurology 2014; 83: 278-286.
Ward MA, Bendlin BB, McLaren DG, et al. Low HDL cholesterol is associated with lower gray matter volume in cognitively healthy adults. Front Aging Neurosci 2010; 2.
Hottman DA, Chernick D, Cheng S, Wang Z, Li L. HDL and cognition in neurodegenerative disorders. Neurobiol Dis 2014; Pt 72 A: 22-36.
Wang H, Eckel RH. Lipoprotein lipase in the brain and nervous system. Annu Rev Nutr 2012; 32: 147-160.
Tani M, Horvath KV, Lamarche B, et al. High-density lipoprotein subpopulation profiles in lipoprotein lipase and hepatic lipase deficiency. Atherosclerosis 2016; 253: 7-14.
Ayyappa KA, Shatwan I, Bodhini D, et al. High fat diet modifies the association of lipoprotein lipase gene polymorphism with high density lipoprotein cholesterol in an Asian Indian population. Nutr Metab (Lond) 2017; 14: 8.