Tau seeds from Alzheimer's disease brains trigger tau spread in macaques while oligomeric-Aβ mediates pathology maturation.
Alzheimer's disease
beta-amyloid
non-human primate
prion-like
tau
tauopathy
Journal
Alzheimer's & dementia : the journal of the Alzheimer's Association
ISSN: 1552-5279
Titre abrégé: Alzheimers Dement
Pays: United States
ID NLM: 101231978
Informations de publication
Date de publication:
Mar 2024
Mar 2024
Historique:
revised:
15
11
2023
received:
06
07
2023
accepted:
17
11
2023
medline:
18
3
2024
pubmed:
27
12
2023
entrez:
27
12
2023
Statut:
ppublish
Résumé
The "prion-like" features of Alzheimer's disease (AD) tauopathy and its relationship with amyloid-β (Aβ) have never been experimentally studied in primates phylogenetically close to humans. We injected 17 macaques in the entorhinal cortex with nanograms of seeding-competent tau aggregates purified from AD brains or control extracts from aged-matched healthy brains, with or without intracerebroventricular co-injections of oligomeric-Aβ. Pathological tau injection increased cerebrospinal fluid (CSF) p-tau181 concentration after 18 months. Tau pathology spreads from the entorhinal cortex to the hippocampal trisynaptic loop and the cingulate cortex, resuming the experimental progression of Braak stage I to IV. Many AD-related molecular networks were impacted by tau seeds injections regardless of Aβ injections in proteomic analyses. However, we found mature neurofibrillary tangles, increased CSF total-tau concentration, and pre- and postsynaptic degeneration only in Aβ co-injected macaques. Oligomeric-Aβ mediates the maturation of tau pathology and its neuronal toxicity in macaques but not its initial spreading. This study supports the "prion-like" properties of misfolded tau extracted from AD brains. This study empirically validates the Braak staging in an anthropomorphic brain. This study highlights the role of oligomeric Aβ in driving the maturation and toxicity of tau pathology. This work establishes a novel animal model of early sporadic AD that is closer to the human pathology.
Substances chimiques
tau Proteins
0
Amyloid beta-Peptides
0
Prions
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
1894-1912Subventions
Organisme : Wellcome Trust
ID : 206248/Z/17/Z
Pays : United Kingdom
Informations de copyright
© 2024 The Authors. Alzheimer's & Dementia published by Wiley Periodicals LLC on behalf of Alzheimer's Association.
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