Continuous Monitoring of Tau-Induced Neurotoxicity in Patient-Derived iPSC-Neurons.
Alzheimer's disease
FTLD
MAPT
PSEN1 L435F
iPSC
neurotoxicity
tau aggregation
tau seeding
Journal
The Journal of neuroscience : the official journal of the Society for Neuroscience
ISSN: 1529-2401
Titre abrégé: J Neurosci
Pays: United States
ID NLM: 8102140
Informations de publication
Date de publication:
12 05 2021
12 05 2021
Historique:
received:
06
10
2020
revised:
12
02
2021
accepted:
19
02
2021
pubmed:
25
4
2021
medline:
23
11
2021
entrez:
24
4
2021
Statut:
ppublish
Résumé
Tau aggregation within neurons is a critical feature of Alzheimer's disease (AD) and related tauopathies. It is believed that soluble pathologic tau species seed the formation of tau aggregates in a prion-like manner and propagate through connected neurons during the progression of disease. Both soluble and aggregated forms of tau are thought to have neurotoxic properties. In addition, different strains of misfolded tau may cause differential neurotoxicity. In this work, we present an accelerated human neuronal model of tau-induced neurotoxicity that incorporates both soluble tau species and tau aggregation. Using patient-derived induced pluripotent stem cell (iPSC) neurons expressing a tau aggregation biosensor, we develop a cell culture system that allows continuous assessment of both induced tau aggregation and neuronal viability at single-cell resolution for periods of >1 week. We show that exogenous tau "seed" uptake, as measured by tau repeat domain (TauRD) reporter aggregation, increases the risk for subsequent neuronal death
Identifiants
pubmed: 33893219
pii: JNEUROSCI.2590-20.2021
doi: 10.1523/JNEUROSCI.2590-20.2021
pmc: PMC8143197
doi:
Substances chimiques
MAPT protein, human
0
PSEN1 protein, human
0
Presenilin-1
0
tau Proteins
0
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
4335-4348Subventions
Organisme : NIA NIH HHS
ID : P30 AG062421
Pays : United States
Organisme : NIA NIH HHS
ID : R01 AG058002
Pays : United States
Organisme : NIA NIH HHS
ID : RF1 AG058674
Pays : United States
Organisme : NIA NIH HHS
ID : RF1 AG059789
Pays : United States
Informations de copyright
Copyright © 2021 Oakley et al.
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