Aβ42 oligomers trigger synaptic loss through CAMKK2-AMPK-dependent effectors coordinating mitochondrial fission and mitophagy.
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
01 08 2022
01 08 2022
Historique:
received:
20
01
2020
accepted:
18
07
2022
entrez:
1
8
2022
pubmed:
2
8
2022
medline:
4
8
2022
Statut:
epublish
Résumé
During the early stages of Alzheimer's disease (AD) in both mouse models and human patients, soluble forms of Amyloid-β 1-42 oligomers (Aβ42o) trigger loss of excitatory synapses (synaptotoxicity) in cortical and hippocampal pyramidal neurons (PNs) prior to the formation of insoluble amyloid plaques. In a transgenic AD mouse model, we observed a spatially restricted structural remodeling of mitochondria in the apical tufts of CA1 PNs dendrites corresponding to the dendritic domain where the earliest synaptic loss is detected in vivo. We also observed AMPK over-activation as well as increased fragmentation and loss of mitochondrial biomass in Ngn2-induced neurons derived from a new APP
Identifiants
pubmed: 35915085
doi: 10.1038/s41467-022-32130-5
pii: 10.1038/s41467-022-32130-5
pmc: PMC9343354
doi:
Substances chimiques
Amyloid beta-Peptides
0
Peptide Fragments
0
amyloid beta-protein (1-42)
0
Calcium-Calmodulin-Dependent Protein Kinase Kinase
EC 2.7.11.17
Camkk2 protein, mouse
EC 2.7.11.17
AMP-Activated Protein Kinases
EC 2.7.11.31
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
4444Subventions
Organisme : NINDS NIH HHS
ID : K99 NS091526
Pays : United States
Organisme : NCI NIH HHS
ID : P30 CA014195
Pays : United States
Organisme : NINDS NIH HHS
ID : R01 NS089456
Pays : United States
Organisme : NINDS NIH HHS
ID : R35 NS127232
Pays : United States
Informations de copyright
© 2022. The Author(s).
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