Home > Publications Database > Gliovascular transcriptional perturbations in Alzheimer's disease reveal molecular mechanisms of blood brain barrier dysfunction. > print

001     270417
005     20240808164304.0
024 7 _ |a pmc:PMC11190273
|2 pmc
024 7 _ |a 10.1038/s41467-024-48926-6
|2 doi
024 7 _ |a pmid:38902234
|2 pmid
024 7 _ |a altmetric:164686318
|2 altmetric
037 _ _ |a DZNE-2024-00797
041 _ _ |a English
082 _ _ |a 500
100 1 _ |a İş, Özkan
|0 0000-0003-4070-6756
|b 0
245 _ _ |a Gliovascular transcriptional perturbations in Alzheimer's disease reveal molecular mechanisms of blood brain barrier dysfunction.
260 _ _ |a [London]
|c 2024
|b Nature Publishing Group UK
336 7 _ |a article
|2 DRIVER
336 7 _ |a Output Types/Journal article
|2 DataCite
336 7 _ |a Journal Article
|b journal
|m journal
|0 PUB:(DE-HGF)16
|s 1718977551_18077
|2 PUB:(DE-HGF)
336 7 _ |a ARTICLE
|2 BibTeX
336 7 _ |a JOURNAL_ARTICLE
|2 ORCID
336 7 _ |a Journal Article
|0 0
|2 EndNote
520 _ _ |a To uncover molecular changes underlying blood-brain-barrier dysfunction in Alzheimer's disease, we performed single nucleus RNA sequencing in 24 Alzheimer's disease and control brains and focused on vascular and astrocyte clusters as main cell types of blood-brain-barrier gliovascular-unit. The majority of the vascular transcriptional changes were in pericytes. Of the vascular molecular targets predicted to interact with astrocytic ligands, SMAD3, upregulated in Alzheimer's disease pericytes, has the highest number of ligands including VEGFA, downregulated in Alzheimer's disease astrocytes. We validated these findings with external datasets comprising 4,730 pericyte and 150,664 astrocyte nuclei. Blood SMAD3 levels are associated with Alzheimer's disease-related neuroimaging outcomes. We determined inverse relationships between pericytic SMAD3 and astrocytic VEGFA in human iPSC and zebrafish models. Here, we detect vast transcriptome changes in Alzheimer's disease at the gliovascular-unit, prioritize perturbed pericytic SMAD3-astrocytic VEGFA interactions, and validate these in cross-species models to provide a molecular mechanism of blood-brain-barrier disintegrity in Alzheimer's disease.
536 _ _ |a 352 - Disease Mechanisms (POF4-352)
|0 G:(DE-HGF)POF4-352
|c POF4-352
|f POF IV
|x 0
588 _ _ |a Dataset connected to CrossRef, PubMed, , Journals: pub.dzne.de
650 _ 7 |a Smad3 Protein
|2 NLM Chemicals
650 _ 7 |a Vascular Endothelial Growth Factor A
|2 NLM Chemicals
650 _ 7 |a SMAD3 protein, human
|2 NLM Chemicals
650 _ 7 |a VEGFA protein, human
|2 NLM Chemicals
650 _ 2 |a Alzheimer Disease: genetics
|2 MeSH
650 _ 2 |a Alzheimer Disease: metabolism
|2 MeSH
650 _ 2 |a Alzheimer Disease: pathology
|2 MeSH
650 _ 2 |a Humans
|2 MeSH
650 _ 2 |a Blood-Brain Barrier: metabolism
|2 MeSH
650 _ 2 |a Blood-Brain Barrier: pathology
|2 MeSH
650 _ 2 |a Smad3 Protein: metabolism
|2 MeSH
650 _ 2 |a Smad3 Protein: genetics
|2 MeSH
650 _ 2 |a Zebrafish
|2 MeSH
650 _ 2 |a Astrocytes: metabolism
|2 MeSH
650 _ 2 |a Vascular Endothelial Growth Factor A: metabolism
|2 MeSH
650 _ 2 |a Vascular Endothelial Growth Factor A: genetics
|2 MeSH
650 _ 2 |a Animals
|2 MeSH
650 _ 2 |a Pericytes: metabolism
|2 MeSH
650 _ 2 |a Pericytes: pathology
|2 MeSH
650 _ 2 |a Male
|2 MeSH
650 _ 2 |a Induced Pluripotent Stem Cells: metabolism
|2 MeSH
650 _ 2 |a Female
|2 MeSH
650 _ 2 |a Aged
|2 MeSH
650 _ 2 |a Transcriptome
|2 MeSH
650 _ 2 |a Brain: metabolism
|2 MeSH
650 _ 2 |a Brain: pathology
|2 MeSH
650 _ 2 |a Brain: blood supply
|2 MeSH
650 _ 2 |a Aged, 80 and over
|2 MeSH
650 _ 2 |a Disease Models, Animal
|2 MeSH
700 1 _ |a Wang, Xue
|0 0000-0003-1964-4124
|b 1
700 1 _ |a Reddy, Joseph S
|0 0000-0002-1783-4453
|b 2
700 1 _ |a Min, Yuhao
|0 0000-0001-8775-8743
|b 3
700 1 _ |a Yilmaz, Elanur
|0 0000-0001-7045-5068
|b 4
700 1 _ |a Bhattarai, Prabesh
|0 P:(DE-2719)2811306
|b 5
|u dzne
700 1 _ |a Patel, Tulsi
|b 6
700 1 _ |a Bergman, Jeremiah
|b 7
700 1 _ |a Quicksall, Zachary
|0 0000-0002-8791-0925
|b 8
700 1 _ |a Heckman, Michael G
|b 9
700 1 _ |a Tutor-New, Frederick Q
|b 10
700 1 _ |a Can Demirdogen, Birsen
|0 0000-0002-1536-6123
|b 11
700 1 _ |a White, Launia
|b 12
700 1 _ |a Koga, Shunsuke
|0 0000-0001-8868-9700
|b 13
700 1 _ |a Krause, Vincent
|b 14
700 1 _ |a Inoue, Yasuteru
|b 15
700 1 _ |a Kanekiyo, Takahisa
|0 0000-0001-6751-9374
|b 16
700 1 _ |a Cosacak, Mehmet Ilyas
|0 P:(DE-2719)2811286
|b 17
700 1 _ |a Nelson, Nastasia
|b 18
700 1 _ |a Lee, Annie J
|b 19
700 1 _ |a Vardarajan, Badri
|0 0000-0002-5560-4085
|b 20
700 1 _ |a Mayeux, Richard
|b 21
700 1 _ |a Kouri, Naomi
|0 0000-0002-6841-9882
|b 22
700 1 _ |a Deniz, Kaancan
|0 0000-0002-5496-0598
|b 23
700 1 _ |a Carnwath, Troy
|b 24
700 1 _ |a Oatman, Stephanie R
|b 25
700 1 _ |a Lewis-Tuffin, Laura J
|0 0000-0002-6013-8322
|b 26
700 1 _ |a Nguyen, Thuy
|0 0000-0001-8879-7090
|b 27
700 1 _ |a Initiative, Alzheimer’s Disease Neuroimaging
|b 28
|e Collaboration Author
700 1 _ |a Carrasquillo, Minerva M
|0 0000-0002-3231-9134
|b 29
700 1 _ |a Graff-Radford, Jonathan
|b 30
700 1 _ |a Petersen, Ronald C
|0 0000-0002-8178-6601
|b 31
700 1 _ |a Jr Jack, Clifford R
|0 0000-0001-7916-622X
|b 32
700 1 _ |a Kantarci, Kejal
|b 33
700 1 _ |a Murray, Melissa E
|0 0000-0001-7379-2545
|b 34
700 1 _ |a Nho, Kwangsik
|b 35
700 1 _ |a Saykin, Andrew J
|0 0000-0002-1376-8532
|b 36
700 1 _ |a Dickson, Dennis W
|0 0000-0001-7189-7917
|b 37
700 1 _ |a Kizil, Caghan
|0 P:(DE-2719)2811030
|b 38
|u dzne
700 1 _ |a Allen, Mariet
|0 0000-0002-2685-427X
|b 39
700 1 _ |a Ertekin-Taner, Nilüfer
|0 0000-0003-4436-8889
|b 40
773 _ _ |a 10.1038/s41467-024-48926-6
|g Vol. 15, no. 1, p. 4758
|0 PERI:(DE-600)2553671-0
|n 1
|p 4758
|t Nature Communications
|v 15
|y 2024
|x 2041-1723
856 4 _ |y OpenAccess
|u https://pub.dzne.de/record/270417/files/DZNE-2024-00797.pdf
856 4 _ |y OpenAccess
|x pdfa
|u https://pub.dzne.de/record/270417/files/DZNE-2024-00797.pdf?subformat=pdfa
909 C O |o oai:pub.dzne.de:270417
|p openaire
|p open_access
|p VDB
|p driver
|p dnbdelivery
910 1 _ |a External Institute
|0 I:(DE-HGF)0
|k Extern
|b 5
|6 P:(DE-2719)2811306
910 1 _ |a Deutsches Zentrum für Neurodegenerative Erkrankungen
|0 I:(DE-588)1065079516
|k DZNE
|b 17
|6 P:(DE-2719)2811286
910 1 _ |a External Institute
|0 I:(DE-HGF)0
|k Extern
|b 38
|6 P:(DE-2719)2811030
913 1 _ |a DE-HGF
|b Gesundheit
|l Neurodegenerative Diseases
|1 G:(DE-HGF)POF4-350
|0 G:(DE-HGF)POF4-352
|3 G:(DE-HGF)POF4
|2 G:(DE-HGF)POF4-300
|4 G:(DE-HGF)POF
|v Disease Mechanisms
|x 0
914 1 _ |y 2024
915 _ _ |a DBCoverage
|0 StatID:(DE-HGF)0150
|2 StatID
|b Web of Science Core Collection
|d 2023-08-29
915 _ _ |a DBCoverage
|0 StatID:(DE-HGF)1040
|2 StatID
|b Zoological Record
|d 2023-08-29
915 _ _ |a DBCoverage
|0 StatID:(DE-HGF)1060
|2 StatID
|b Current Contents - Agriculture, Biology and Environmental Sciences
|d 2023-08-29
915 _ _ |a DBCoverage
|0 StatID:(DE-HGF)0501
|2 StatID
|b DOAJ Seal
|d 2023-05-02T09:09:09Z
915 _ _ |a DBCoverage
|0 StatID:(DE-HGF)1030
|2 StatID
|b Current Contents - Life Sciences
|d 2023-08-29
915 _ _ |a Article Processing Charges
|0 StatID:(DE-HGF)0561
|2 StatID
|d 2023-08-29
915 _ _ |a Creative Commons Attribution CC BY (No Version)
|0 LIC:(DE-HGF)CCBYNV
|2 V:(DE-HGF)
|b DOAJ
|d 2023-05-02T09:09:09Z
915 _ _ |a WoS
|0 StatID:(DE-HGF)0113
|2 StatID
|b Science Citation Index Expanded
|d 2023-08-29
915 _ _ |a DBCoverage
|0 StatID:(DE-HGF)1150
|2 StatID
|b Current Contents - Physical, Chemical and Earth Sciences
|d 2023-08-29
915 _ _ |a Fees
|0 StatID:(DE-HGF)0700
|2 StatID
|d 2023-08-29
915 _ _ |a DBCoverage
|0 StatID:(DE-HGF)0200
|2 StatID
|b SCOPUS
|d 2023-08-29
915 _ _ |a DBCoverage
|0 StatID:(DE-HGF)1050
|2 StatID
|b BIOSIS Previews
|d 2023-08-29
915 _ _ |a JCR
|0 StatID:(DE-HGF)0100
|2 StatID
|b NAT COMMUN : 2022
|d 2023-08-29
915 _ _ |a DBCoverage
|0 StatID:(DE-HGF)0500
|2 StatID
|b DOAJ
|d 2023-05-02T09:09:09Z
915 _ _ |a OpenAccess
|0 StatID:(DE-HGF)0510
|2 StatID
915 _ _ |a DBCoverage
|0 StatID:(DE-HGF)0300
|2 StatID
|b Medline
|d 2023-08-29
915 _ _ |a DBCoverage
|0 StatID:(DE-HGF)1190
|2 StatID
|b Biological Abstracts
|d 2023-08-29
915 _ _ |a IF >= 15
|0 StatID:(DE-HGF)9915
|2 StatID
|b NAT COMMUN : 2022
|d 2023-08-29
915 _ _ |a DBCoverage
|0 StatID:(DE-HGF)0199
|2 StatID
|b Clarivate Analytics Master Journal List
|d 2023-08-29
915 _ _ |a Peer Review
|0 StatID:(DE-HGF)0030
|2 StatID
|b DOAJ : Peer review
|d 2023-05-02T09:09:09Z
915 _ _ |a DBCoverage
|0 StatID:(DE-HGF)0160
|2 StatID
|b Essential Science Indicators
|d 2023-08-29
915 _ _ |a DBCoverage
|0 StatID:(DE-HGF)0320
|2 StatID
|b PubMed Central
|d 2023-08-29
920 1 _ |0 I:(DE-2719)1710007
|k AG Kizil
|l Mechanisms of Induced Plasticity of the Vertebrate Brain
|x 0
980 _ _ |a journal
980 _ _ |a VDB
980 _ _ |a UNRESTRICTED
980 _ _ |a I:(DE-2719)1710007
980 1 _ |a FullTexts

LibraryCollectionCLSMajorCLSMinorLanguageAuthor
Marc 21