Integrative approach to sporadic Alzheimer's disease: deficiency of TYROBP in cerebral Aβ amyloidosis mouse normalizes clinical phenotype and complement subnetwork molecular pathology without reducing Aβ burden.
Adaptor Proteins, Signal Transducing
/ deficiency
Alzheimer Disease
/ genetics
Amyloid beta-Peptides
/ genetics
Amyloid beta-Protein Precursor
/ genetics
Amyloidosis
/ genetics
Animals
Brain
/ metabolism
Disease Models, Animal
Female
Gene Regulatory Networks
Humans
Male
Membrane Proteins
/ deficiency
Mice
Mice, Inbred C57BL
Mice, Knockout
Pathology, Molecular
/ methods
Phenotype
Plaque, Amyloid
/ pathology
Transcriptome
Journal
Molecular psychiatry
ISSN: 1476-5578
Titre abrégé: Mol Psychiatry
Pays: England
ID NLM: 9607835
Informations de publication
Date de publication:
03 2019
03 2019
Historique:
received:
09
04
2018
accepted:
15
08
2018
pubmed:
5
10
2018
medline:
4
12
2019
entrez:
5
10
2018
Statut:
ppublish
Résumé
Integrative gene network approaches enable new avenues of exploration that implicate causal genes in sporadic late-onset Alzheimer's disease (LOAD) pathogenesis, thereby offering novel insights for drug-discovery programs. We previously constructed a probabilistic causal network model of sporadic LOAD and identified TYROBP/DAP12, encoding a microglial transmembrane signaling polypeptide and direct adapter of TREM2, as the most robust key driver gene in the network. Here, we show that absence of TYROBP/DAP12 in a mouse model of AD-type cerebral Aβ amyloidosis (APP
Identifiants
pubmed: 30283032
doi: 10.1038/s41380-018-0255-6
pii: 10.1038/s41380-018-0255-6
pmc: PMC6494440
mid: NIHMS1504011
doi:
Substances chimiques
Adaptor Proteins, Signal Transducing
0
Amyloid beta-Peptides
0
Amyloid beta-Protein Precursor
0
Membrane Proteins
0
TYROBP protein, human
0
Tyrobp protein, mouse
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
431-446Subventions
Organisme : NIA NIH HHS
ID : RF1 AG058469
Pays : United States
Organisme : NIA NIH HHS
ID : R56 AG058469
Pays : United States
Organisme : NIA NIH HHS
ID : R01 AG061894
Pays : United States
Organisme : NIA NIH HHS
ID : R01 AG017917
Pays : United States
Organisme : NIA NIH HHS
ID : RF1 AG059319
Pays : United States
Organisme : NIA NIH HHS
ID : P30 AG010161
Pays : United States
Organisme : NIA NIH HHS
ID : RF1 AG057443
Pays : United States
Organisme : NIA NIH HHS
ID : P50 AG005138
Pays : United States
Organisme : NIA NIH HHS
ID : P30 AG066514
Pays : United States
Organisme : NIA NIH HHS
ID : U01 AG046170
Pays : United States
Organisme : NIA NIH HHS
ID : R01 AG057907
Pays : United States
Commentaires et corrections
Type : ErratumIn
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