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Zhao, N.* ; Ren, Y.* ; Yamazaki, Y.* ; Qiao, W.* ; Li, F.* ; Felton, L.M.* ; MahmoudianDehkordi, S.* ; Kueider-Paisley, A.* ; Sonoustoun, B.* ; Arnold, M. ; Shue, F.* ; Zheng, J.* ; Attrebi, O.N.* ; Martens, Y.A.* ; Li, Z.* ; Bastea, L.* ; Meneses, A.D.* ; Chen, K.* ; Thompson, K.* ; St John-Williams, L.* ; Tachibana, M.* ; Aikawa, T.* ; Oue, H.* ; Job, L.* ; Yamazaki, A.* ; Liu, C.C.* ; Storz, P.* ; Asmann, Y.W.* ; Ertekin-Taner, N.* ; Kanekiyo, T.* ; Kaddurah-Daouk, R.* ; Bu, G.*

Alzheimer's risk factors age, APOE genotype, and sex drive distinct. 3 molecular pathways.

Neuron 106, 727-742 (2020)
Postprint Research data DOI PMC
Open Access Green
Evidence suggests interplay among the three major risk factors for Alzheimer's disease (AD): age, APOE genotype, and sex. Here, we present comprehensive datasets and analyses of brain transcriptomes and blood metabolomes from human apoE2-, apoE3-, and apoE4-targeted replacement mice across young, middle, and old ages with both sexes. We found that age had the greatest impact on brain transcriptomes highlighted by an immune module led by Trem2 and Tyrobp, whereas APOE4 was associated with upregulation of multiple Serpina3 genes. Importantly, these networks and gene expression changes were mostly conserved in human brains. Finally, we observed a significant interaction between age, APOE genotype, and sex on unfolded protein response pathway. In the periphery, APOE2 drove distinct blood metabolome profile highlighted by the upregulation of lipid metabolites. Our work identifies unique and interactive molecular pathways underlying AD risk factors providing valuable resources for discovery and validation research in model systems and humans.
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Publication type Article: Journal article
Document type Scientific Article
Keywords Age ; Alzheimer's Disease ; Apoe ; Extracellular Vesicles ; Inflammation ; Lipid Metabolism ; Metabolomics ; Serpina3 ; Sex ; Transcriptomics; Apolipoprotein-e Genotype; Unfolded Protein Response; Amyloid Deposits; United-states; A-beta; Disease; Alpha-1-antichymotrypsin; Brain; Microglia; Receptors
Language english
Publication Year 2020
HGF-reported in Year 2020
ISSN (print) / ISBN 0896-6273
e-ISSN 1097-4199
Journal Neuron
Quellenangaben Volume: 106, Issue: 5, Pages: 727-742 Article Number: , Supplement: ,
Publisher Cell Press
Publishing Place Cambridge, Mass.
Reviewing status Peer reviewed
Institute(s) Institute of Computational Biology (ICB)
POF-Topic(s) 30205 - Bioengineering and Digital Health
Research field(s) Enabling and Novel Technologies
PSP Element(s) G-503891-001
DOI 10.1016/j.neuron.2020.02.034
WOS ID WOS:000538777500007
Scopus ID 85082824401
PubMed ID 32199103
Erfassungsdatum 2020-05-26
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