Golgi fragmentation - One of the earliest organelle phenotypes in Alzheimer's disease neurons.
Alzheimer’s disease
Golgi fragmentation
disease modelling
hiPSC
neurons
Journal
Frontiers in neuroscience
ISSN: 1662-4548
Titre abrégé: Front Neurosci
Pays: Switzerland
ID NLM: 101478481
Informations de publication
Date de publication:
2023
2023
Historique:
received:
09
12
2022
accepted:
30
01
2023
entrez:
6
3
2023
pubmed:
7
3
2023
medline:
7
3
2023
Statut:
epublish
Résumé
Alzheimer's disease (AD) is the most common cause of dementia, with no current cure. Consequently, alternative approaches focusing on early pathological events in specific neuronal populations, besides targeting the well-studied amyloid beta (Aβ) accumulations and Tau tangles, are needed. In this study, we have investigated disease phenotypes specific to glutamatergic forebrain neurons and mapped the timeline of their occurrence, by implementing familial and sporadic human induced pluripotent stem cell models as well as the 5xFAD mouse model. We recapitulated characteristic late AD phenotypes, such as increased Aβ secretion and Tau hyperphosphorylation, as well as previously well documented mitochondrial and synaptic deficits. Intriguingly, we identified Golgi fragmentation as one of the earliest AD phenotypes, indicating potential impairments in protein processing and post-translational modifications. Computational analysis of RNA sequencing data revealed differentially expressed genes involved in glycosylation and glycan patterns, whilst total glycan profiling revealed minor glycosylation differences. This indicates general robustness of glycosylation besides the observed fragmented morphology. Importantly, we identified that genetic variants in Sortilin-related receptor 1 (
Identifiants
pubmed: 36875643
doi: 10.3389/fnins.2023.1120086
pmc: PMC9978754
doi:
Types de publication
Journal Article
Langues
eng
Pagination
1120086Informations de copyright
Copyright © 2023 Haukedal, Corsi, Gadekar, Doncheva, Kedia, de Haan, Chandrasekaran, Jensen, Schiønning, Vallin, Marlet, Poon, Pires, Agha, Wandall, Cirera, Simonsen, Nielsen, Nielsen, Hyttel, Muddashetty, Aldana, Gorodkin, Nair, Meyer, Larsen and Freude.
Déclaration de conflit d'intérêts
HW owns stocks and is a consultant for and co-founder of EbuMab ApS, Hemab ApS, and GO- Therapeutics, Inc., all not involved in, or related to, the research performed in this study. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
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