Distinct patterns of apolipoprotein C-I, C-II, and C-III isoforms are associated with markers of Alzheimer's disease.
CSF
amyloid-β42
apoC-I
apoC-II
apoC-III
apoE
apolipoproteins
mass spectrometry
plasma
proteomics
Journal
Journal of lipid research
ISSN: 1539-7262
Titre abrégé: J Lipid Res
Pays: United States
ID NLM: 0376606
Informations de publication
Date de publication:
2021
2021
Historique:
received:
19
05
2020
revised:
09
12
2020
accepted:
11
12
2020
pubmed:
2
2
2021
medline:
11
3
2022
entrez:
1
2
2021
Statut:
ppublish
Résumé
Apolipoproteins C-I, C-II, and C-III interact with ApoE to regulate lipoprotein metabolism and contribute to Alzheimer's disease pathophysiology. In plasma, apoC-I and C-II exist as truncated isoforms, while apoC-III exhibits multiple glycoforms. This study aimed to 1) delineate apoC-I, C-II, and C-III isoform profiles in cerebrospinal fluid (CSF) and plasma in a cohort of nondemented older individuals (n = 61), and 2) examine the effect of APOE4 on these isoforms and their correlation with CSF Aβ42, a surrogate of brain amyloid accumulation. The isoforms of the apoCs were immunoaffinity enriched and measured with MALDI-TOF mass spectrometry, revealing a significantly higher percentage of truncated apoC-I and apoC-II in CSF compared with matched plasma, with positive correlation between CSF and plasma. A greater percentage of monosialylated and disialylated apoC-III isoforms was detected in CSF, accompanied by a lower percentage of the two nonsialylated apoC-III isoforms, with significant linear correlations between CSF and plasma. Furthermore, a greater percentage of truncated apoC-I in CSF and apoC-II in plasma and CSF was observed in individuals carrying at least one APOE Ɛ4 allele. Increased apoC-I and apoC-II truncations were associated with lower CSF Aβ42. Finally, monosialylated apoC-III was lower, and disialylated apoC-III greater in the CSF of Ɛ4 carriers. Together, these results reveal distinct patterns of the apoCs isoforms in CSF, implying CSF-specific apoCs processing. These patterns were accentuated in APOE Ɛ4 allele carriers, suggesting an association between APOE4 genotype and Alzheimer's disease pathology with apoCs processing and function in the brain.
Identifiants
pubmed: 33518512
pii: S0022-2275(20)43718-6
doi: 10.1194/jlr.RA120000919
pmc: PMC7859854
pii:
doi:
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
100014Subventions
Organisme : NIA NIH HHS
ID : P50 AG005142
Pays : United States
Organisme : NIA NIH HHS
ID : R43 AG069552
Pays : United States
Organisme : NIA NIH HHS
ID : R01 AG067063
Pays : United States
Organisme : NIA NIH HHS
ID : R01 AG054434
Pays : United States
Organisme : NIA NIH HHS
ID : R01 AG055770
Pays : United States
Organisme : NIA NIH HHS
ID : R21 AG056518
Pays : United States
Informations de copyright
Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.
Déclaration de conflit d'intérêts
Conflict of interest The authors declare that they have no conflicts of interest with the contents of this article.