Bioenergetic and inflammatory systemic phenotypes in Alzheimer's disease APOE ε4-carriers.
APOE
Alzheimer's disease
bioenergetics
inflammation
mitochondria
Journal
Aging cell
ISSN: 1474-9726
Titre abrégé: Aging Cell
Pays: England
ID NLM: 101130839
Informations de publication
Date de publication:
05 2021
05 2021
Historique:
revised:
03
03
2021
received:
23
12
2020
accepted:
15
03
2021
pubmed:
4
5
2021
medline:
16
12
2021
entrez:
3
5
2021
Statut:
ppublish
Résumé
We examined the impact of an APOE ε4 genotype on Alzheimer's disease (AD) subject platelet and lymphocyte metabolism. Mean platelet mitochondrial cytochrome oxidase Vmax activity was lower in APOE ε4 carriers and lymphocyte Annexin V, a marker of apoptosis, was significantly higher. Proteins that mediate mitophagy and energy sensing were higher in APOE ε4 lymphocytes which could represent compensatory changes and recapitulate phenomena observed in post-mortem AD brains. Analysis of the lipid synthesis pathway found higher AceCSI, ATP CL, and phosphorylated ACC levels in APOE ε4 lymphocytes. Lymphocyte ACC changes were also observed in post-mortem brain tissue. Lymphocyte RNAseq showed lower APOE ε4 carrier sphingolipid Transporter 3 (SPNS3) and integrin Subunit Alpha 1 (ITGA1) expression. RNAseq pathway analysis revealed APOE ε4 alleles activated inflammatory pathways and modulated bioenergetic signaling. These findings support a relationship between APOE genotype and bioenergetic pathways and indicate platelets and lymphocytes from APOE ε4 carriers exist in a state of bioenergetic stress. Neither medication use nor brain-localized AD histopathology can account for these findings, which define an APOE ε4-determined molecular and systemic phenotype that informs AD etiology.
Identifiants
pubmed: 33939248
doi: 10.1111/acel.13356
pmc: PMC8135087
doi:
Substances chimiques
ApoE protein, human
0
Apolipoproteins E
0
Inflammation Mediators
0
Electron Transport Complex IV
EC 1.9.3.1
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
e13356Subventions
Organisme : NIA NIH HHS
ID : P30 AG035982
Pays : United States
Organisme : NIA NIH HHS
ID : R00 AG056600
Pays : United States
Organisme : NIA NIH HHS
ID : P30 AG072973
Pays : United States
Organisme : NIGMS NIH HHS
ID : P20 GM130423
Pays : United States
Organisme : NIA NIH HHS
ID : K99 AG056600
Pays : United States
Informations de copyright
© 2021 The Authors. Aging Cell published by Anatomical Society and John Wiley & Sons Ltd.
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