272136 20250127091553.0 pmc:PMC11480862 pmc 10.1016/j.xgen.2024.100642 doi pmid:39216475 pmid altmetric:166818088 altmetric DZNE-2024-01131 English 610 Tayran, Hüseyin 0 ABCA7-dependent induction of neuropeptide Y is required for synaptic resilience in Alzheimer's disease through BDNF/NGFR signaling. Amsterdam 2024 Elsevier article DRIVER Output Types/Journal article DataCite Journal Article journal journal PUB:(DE-HGF)16 1727089339_25599 PUB:(DE-HGF) ARTICLE BibTeX JOURNAL_ARTICLE ORCID Journal Article 0 EndNote Genetic variants in ABCA7, an Alzheimer's disease (AD)-associated gene, elevate AD risk, yet its functional relevance to the etiology is unclear. We generated a CRISPR-Cas9-mediated abca7 knockout zebrafish to explore ABCA7's role in AD. Single-cell transcriptomics in heterozygous abca7+/- knockout combined with Aβ42 toxicity revealed that ABCA7 is crucial for neuropeptide Y (NPY), brain-derived neurotrophic factor (BDNF), and nerve growth factor receptor (NGFR) expressions, which are crucial for synaptic integrity, astroglial proliferation, and microglial prevalence. Impaired NPY induction decreased BDNF and synaptic density, which are rescuable with ectopic NPY. In induced pluripotent stem cell-derived human neurons exposed to Aβ42, ABCA7-/- suppresses NPY. Clinical data showed reduced NPY in AD correlated with elevated Braak stages, genetic variants in NPY associated with AD, and epigenetic changes in NPY, NGFR, and BDNF promoters linked to ABCA7 variants. Therefore, ABCA7-dependent NPY signaling via BDNF-NGFR maintains synaptic integrity, implicating its impairment in increased AD risk through reduced brain resilience. 352 - Disease Mechanisms (POF4-352) G:(DE-HGF)POF4-352 POF4-352 POF IV 0 Dataset connected to CrossRef, PubMed, , Journals: pub.dzne.de Brain-Derived Neurotrophic Factor NLM Chemicals Neuropeptide Y NLM Chemicals ATP-Binding Cassette Transporters NLM Chemicals Receptors, Nerve Growth Factor NLM Chemicals Zebrafish Proteins NLM Chemicals Amyloid beta-Peptides NLM Chemicals Brain-Derived Neurotrophic Factor: metabolism MeSH Brain-Derived Neurotrophic Factor: genetics MeSH Animals MeSH Alzheimer Disease: metabolism MeSH Alzheimer Disease: genetics MeSH Alzheimer Disease: pathology MeSH Neuropeptide Y: metabolism MeSH Neuropeptide Y: genetics MeSH Humans MeSH Zebrafish MeSH Signal Transduction MeSH Synapses: metabolism MeSH Synapses: pathology MeSH ATP-Binding Cassette Transporters: genetics MeSH ATP-Binding Cassette Transporters: metabolism MeSH Receptors, Nerve Growth Factor: genetics MeSH Receptors, Nerve Growth Factor: metabolism MeSH Zebrafish Proteins: genetics MeSH Zebrafish Proteins: metabolism MeSH Neurons: metabolism MeSH Neurons: pathology MeSH Amyloid beta-Peptides: metabolism MeSH Amyloid beta-Peptides: genetics MeSH Yilmaz, Elanur 1 Bhattarai, Prabesh P:(DE-2719)2811306 2 dzne Min, Yuhao 3 Wang, Xue 4 Ma, Yiyi 5 Wang, Ni 6 Jeong, Inyoung 7 Nelson, Nastasia 8 Kassara, Nada 9 Cosacak, Mehmet Ilyas P:(DE-2719)2811286 10 dzne Dogru, Ruya Merve 11 Reyes-Dumeyer, Dolly 12 Stenersen, Jakob Mørkved 13 Reddy, Joseph S 14 Qiao, Min 15 Flaherty, Delaney 16 Gunasekaran, Tamil Iniyan 17 Yang, Zikun 18 Jurisch-Yaksi, Nathalie 19 Teich, Andrew F 20 Kanekiyo, Takahisa 21 Tosto, Giuseppe 22 Vardarajan, Badri N 23 İş, Özkan 24 Ertekin-Taner, Nilüfer 25 Mayeux, Richard 26 Kizil, Caghan 27 10.1016/j.xgen.2024.100642 Vol. 4, no. 9, p. 100642 - PERI:(DE-600)3110160-4 9 100642 Cell genomics 4 2024 2666-979X http://pub.dzne.de/record/272136/files/DZNE-2024-01131%20SUP.zip OpenAccess http://pub.dzne.de/record/272136/files/DZNE-2024-01131.pdf OpenAccess pdfa http://pub.dzne.de/record/272136/files/DZNE-2024-01131.pdf?subformat=pdfa oai:pub.dzne.de:272136 openaire open_access VDB driver dnbdelivery External Institute I:(DE-HGF)0 Extern 2 P:(DE-2719)2811306 Deutsches Zentrum für Neurodegenerative Erkrankungen I:(DE-588)1065079516 DZNE 10 P:(DE-2719)2811286 DE-HGF Gesundheit Neurodegenerative Diseases G:(DE-HGF)POF4-350 G:(DE-HGF)POF4-352 G:(DE-HGF)POF4 G:(DE-HGF)POF4-300 G:(DE-HGF)POF Disease Mechanisms 0 2024 DBCoverage StatID:(DE-HGF)0200 StatID SCOPUS 2023-08-29 Creative Commons Attribution-NonCommercial-NoDerivs CC BY-NC-ND 4.0 LIC:(DE-HGF)CCBYNCND4 HGFVOC DBCoverage StatID:(DE-HGF)0501 StatID DOAJ Seal 2023-05-09T12:14:04Z DBCoverage StatID:(DE-HGF)0500 StatID DOAJ 2023-05-09T12:14:04Z OpenAccess StatID:(DE-HGF)0510 StatID Peer Review StatID:(DE-HGF)0030 StatID DOAJ : Double anonymous peer review 2023-05-09T12:14:04Z Article Processing Charges StatID:(DE-HGF)0561 StatID 2023-08-29 DBCoverage StatID:(DE-HGF)0300 StatID Medline 2023-08-29 DBCoverage StatID:(DE-HGF)0320 StatID PubMed Central 2023-08-29 Fees StatID:(DE-HGF)0700 StatID 2023-08-29 I:(DE-2719)1710007 AG Kizil Mechanisms of Induced Plasticity of the Vertebrate Brain 0 journal VDB UNRESTRICTED I:(DE-2719)1710007 FullTexts