Transcriptional Signatures of Tau and Amyloid Neuropathology.
Alzheimer’s disease
RNA-seq
amyloid
entorhinal cortex
gene expression
hippocampus
neuropathology
tau
transgenic model
Journal
Cell reports
ISSN: 2211-1247
Titre abrégé: Cell Rep
Pays: United States
ID NLM: 101573691
Informations de publication
Date de publication:
11 02 2020
11 02 2020
Historique:
received:
28
03
2019
revised:
21
11
2019
accepted:
21
01
2020
entrez:
13
2
2020
pubmed:
13
2
2020
medline:
9
3
2021
Statut:
ppublish
Résumé
Alzheimer's disease (AD) is associated with the intracellular aggregation of hyperphosphorylated tau and the accumulation of β-amyloid in the neocortex. We use transgenic mice harboring human tau (rTg4510) and amyloid precursor protein (J20) mutations to investigate transcriptional changes associated with the progression of tau and amyloid pathology. rTg4510 mice are characterized by widespread transcriptional differences in the entorhinal cortex with changes paralleling neuropathological burden across multiple brain regions. Differentially expressed transcripts overlap with genes identified in genetic studies of familial and sporadic AD. Systems-level analyses identify discrete co-expression networks associated with the progressive accumulation of tau that are enriched for genes and pathways previously implicated in AD pathology and overlap with co-expression networks identified in human AD cortex. Our data provide further evidence for an immune-response component in the accumulation of tau and reveal molecular pathways associated with the progression of AD neuropathology.
Identifiants
pubmed: 32049030
pii: S2211-1247(20)30088-7
doi: 10.1016/j.celrep.2020.01.063
pmc: PMC7016505
pii:
doi:
Substances chimiques
Amyloid beta-Peptides
0
tau Proteins
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
2040-2054.e5Subventions
Organisme : Wellcome Trust
ID : WT097835MF
Pays : United Kingdom
Organisme : Biotechnology and Biological Sciences Research Council
ID : BB/K003240/1
Pays : United Kingdom
Organisme : Wellcome Trust
ID : WT101650MA
Pays : United Kingdom
Organisme : Medical Research Council
ID : MC_PC_14127
Pays : United Kingdom
Organisme : Wellcome Trust
Pays : United Kingdom
Organisme : Medical Research Council
ID : MR/M008924/1
Pays : United Kingdom
Informations de copyright
Copyright © 2020 The Author(s). Published by Elsevier Inc. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of Interests T.K.M., Z.A., D.A.C., L.B., and M.J.O. were full-time employees of Eli Lilly & Company Ltd. at the time this work was performed. M.J.O. is currently an employee of AbbVie.
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