{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T10:52:59Z","timestamp":1790247179569,"version":"4.1.0"},"reference-count":105,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2022,5,31]],"date-time":"2022-05-31T00:00:00Z","timestamp":1653955200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Neurogenesis is significantly reduced in Alzheimer\u2019s disease (AD) and is a potential therapeutic target. Contrary to humans, a zebrafish can regenerate its diseased brain, and thus is ideal for studying neurogenesis. To compare the AD-related molecular pathways between humans and zebrafish, we compared single cell or nuclear transcriptomic data from a zebrafish amyloid toxicity model and its controls (N = 12) with the datasets of two human adult brains (N = 10 and N = 48 (Microglia)), and one fetal brain (N = 10). Approximately 95.4% of the human and zebrafish cells co-clustered. Within each cell type, we identified differentially expressed genes (DEGs), enriched KEGG pathways, and gene ontology terms. We studied synergistic and non-synergistic DEGs to point at either common or uniquely altered mechanisms across species. Using the top DEGs, a high concordance in gene expression changes between species was observed in neuronal clusters. On the other hand, the molecular pathways affected by AD in zebrafish astroglia differed from humans in favor of the neurogenic pathways. The integration of zebrafish and human transcriptomes shows that the zebrafish can be used as a tool to study the cellular response to amyloid proteinopathies. Uniquely altered pathways in zebrafish could highlight the specific mechanisms underlying neurogenesis, which are absent in humans, and could serve as potential candidates for therapeutic developments.<\/jats:p>","DOI":"10.3390\/cells11111807","type":"journal-article","created":{"date-parts":[[2022,5,31]],"date-time":"2022-05-31T09:24:29Z","timestamp":1653989069000},"page":"1807","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":46,"title":["Single Cell\/Nucleus Transcriptomics Comparison in Zebrafish and Humans Reveals Common and Distinct Molecular Responses to Alzheimer\u2019s Disease"],"prefix":"10.3390","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2978-3902","authenticated-orcid":false,"given":"Mehmet Ilyas","family":"Cosacak","sequence":"first","affiliation":[{"name":"German Center for Neurodegenerative Diseases (DZNE) Dresden, Helmholtz Association, Tatzberg 41, 01307 Dresden, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Prabesh","family":"Bhattarai","sequence":"additional","affiliation":[{"name":"German Center for Neurodegenerative Diseases (DZNE) Dresden, Helmholtz Association, Tatzberg 41, 01307 Dresden, Germany"},{"name":"Taub Institute for Research on Alzheimer\u2019s Disease and the Aging Brain, Vagelos College of Physicians and Surgeons, Columbia University Irving Medical Center, Columbia University, 630 W 168th St., New York, NY 10032, USA"},{"name":"Department of Neurology, Vagelos College of Physicians and Surgeons, Columbia University Irving Medical Center, Columbia University, 710 W 168th St., New York, NY 10032, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Philip L.","family":"De Jager","sequence":"additional","affiliation":[{"name":"Taub Institute for Research on Alzheimer\u2019s Disease and the Aging Brain, Vagelos College of Physicians and Surgeons, Columbia University Irving Medical Center, Columbia University, 630 W 168th St., New York, NY 10032, USA"},{"name":"Department of Neurology, Vagelos College of Physicians and Surgeons, Columbia University Irving Medical Center, Columbia University, 710 W 168th St., New York, NY 10032, USA"},{"name":"Center for Translational and Computational Neuroimmunology, Department of Neurology, Columbia University Irving Medical Center, Columbia University, 630 W 168th St., New York, NY 10033, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vilas","family":"Menon","sequence":"additional","affiliation":[{"name":"Taub Institute for Research on Alzheimer\u2019s Disease and the Aging Brain, Vagelos College of Physicians and Surgeons, Columbia University Irving Medical Center, Columbia University, 630 W 168th St., New York, NY 10032, USA"},{"name":"Department of Neurology, Vagelos College of Physicians and Surgeons, Columbia University Irving Medical Center, Columbia University, 710 W 168th St., New York, NY 10032, USA"},{"name":"Center for Translational and Computational Neuroimmunology, Department of Neurology, Columbia University Irving Medical Center, Columbia University, 630 W 168th St., New York, NY 10033, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giuseppe","family":"Tosto","sequence":"additional","affiliation":[{"name":"Taub Institute for Research on Alzheimer\u2019s Disease and the Aging Brain, Vagelos College of Physicians and Surgeons, Columbia University Irving Medical Center, Columbia University, 630 W 168th St., New York, NY 10032, USA"},{"name":"Department of Neurology, Vagelos College of Physicians and Surgeons, Columbia University Irving Medical Center, Columbia University, 710 W 168th St., New York, NY 10032, USA"},{"name":"Gertrude H. Sergievsky Center, Vagelos College of Physicians and Surgeons, Columbia University Irving Medical Center, Columbia University, 710 W 168th St., New York, NY 10033, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8164-9762","authenticated-orcid":false,"given":"Caghan","family":"Kizil","sequence":"additional","affiliation":[{"name":"German Center for Neurodegenerative Diseases (DZNE) Dresden, Helmholtz Association, Tatzberg 41, 01307 Dresden, Germany"},{"name":"Taub Institute for Research on Alzheimer\u2019s Disease and the Aging Brain, Vagelos College of Physicians and Surgeons, Columbia University Irving Medical Center, Columbia University, 630 W 168th St., New York, NY 10032, USA"},{"name":"Department of Neurology, Vagelos College of Physicians and Surgeons, Columbia University Irving Medical Center, Columbia University, 710 W 168th St., New York, NY 10032, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,5,31]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"603","DOI":"10.1016\/j.cell.2015.12.056","article-title":"The Cellular Phase of Alzheimer\u2019s Disease","volume":"164","author":"Karran","year":"2016","journal-title":"Cell"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"388","DOI":"10.1016\/S1474-4422(15)70016-5","article-title":"Neuroinflammation in Alzheimer\u2019s disease","volume":"14","author":"Heneka","year":"2015","journal-title":"Lancet Neurol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"900","DOI":"10.1038\/nature02264","article-title":"Folding proteins in fatal ways","volume":"426","author":"Selkoe","year":"2003","journal-title":"Nature"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"789","DOI":"10.1126\/science.1074069","article-title":"Alzheimer\u2019s disease is a synaptic failure","volume":"298","author":"Selkoe","year":"2002","journal-title":"Science"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"741","DOI":"10.1152\/physrev.2001.81.2.741","article-title":"Alzheimer\u2019s disease: Genes, proteins, and therapy","volume":"81","author":"Selkoe","year":"2001","journal-title":"Physiol. 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