Effect of ApoE isoforms on mitochondria in Alzheimer disease.
Aged
Aged, 80 and over
Alzheimer Disease
/ genetics
Apolipoprotein E4
/ genetics
Apolipoproteins E
/ physiology
Brain Chemistry
Female
Humans
Male
Mental Status and Dementia Tests
Mitochondria
/ metabolism
Mitochondrial Dynamics
Mitochondrial Proteins
/ analysis
Nerve Tissue Proteins
/ analysis
Neuronal Plasticity
/ genetics
Organelle Biogenesis
Oxidative Stress
Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha
/ analysis
Protein Isoforms
/ physiology
Sirtuin 3
/ analysis
Verbal Learning
Journal
Neurology
ISSN: 1526-632X
Titre abrégé: Neurology
Pays: United States
ID NLM: 0401060
Informations de publication
Date de publication:
09 06 2020
09 06 2020
Historique:
received:
13
08
2019
accepted:
26
12
2019
pubmed:
28
5
2020
medline:
25
9
2020
entrez:
28
5
2020
Statut:
ppublish
Résumé
To test the hypothesis that ApoE isoforms affect mitochondrial structure and function that are related to cognitive impairment in Alzheimer disease (AD), we systematically investigated the effects of ApoE isoforms on mitochondrial biogenesis and dynamics, oxidative stress, synapses, and cognitive performance in AD. We obtained postmortem human brain tissues and measured proteins that are responsible for mitochondrial biogenesis (peroxisome proliferator-activated receptor-gamma coactivator-1α [PGC-1α] and sirtuin 3 [SIRT3]), for mitochondrial dynamics (mitofusin 1 [MFN1], mitofusin 2 [MFN2], and dynamin-like protein 1 [DLP1]), for oxidative stress (superoxide dismutase 2 [SOD2] and forkhead-box protein O3a [Foxo3a]), and for synapses (postsynaptic density protein 95 [PSD95] and synapsin1 [Syn1]). A total of 46 cases were enrolled, including ApoE-ɛ4 carriers (n = 21) and noncarriers (n = 25). Levels of these proteins were compared between ApoE-ɛ4 carriers and noncarriers. ApoE-ɛ4 was associated with impaired mitochondrial structure and function, oxidative stress, and synaptic integrity in the human brain. Correlation analysis revealed that mitochondrial proteins and the synaptic protein were strongly associated with cognitive performance. ApoE isoforms influence mitochondrial structure and function, which likely leads to alteration in oxidative stress, synapses, and cognitive function. These mitochondria-related proteins may be a harbinger of cognitive decline in ApoE-ɛ4 carriers and provide novel therapeutic targets for prevention and treatment of AD.
Identifiants
pubmed: 32457210
pii: WNL.0000000000009582
doi: 10.1212/WNL.0000000000009582
pmc: PMC7455369
doi:
Substances chimiques
ApoE protein, human
0
Apolipoprotein E4
0
Apolipoproteins E
0
Mitochondrial Proteins
0
Nerve Tissue Proteins
0
PPARGC1A protein, human
0
Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha
0
Protein Isoforms
0
SIRT3 protein, human
EC 3.5.1.-
Sirtuin 3
EC 3.5.1.-
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
e2404-e2411Subventions
Organisme : NIA NIH HHS
ID : P30 AG019610
Pays : United States
Organisme : NINDS NIH HHS
ID : U24 NS072026
Pays : United States
Commentaires et corrections
Type : CommentIn
Informations de copyright
© 2020 American Academy of Neurology.
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