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Unit of Institut d\u2019Investigacions Biom\u00e8diques de Barcelona (IIBB\/CSIC)","award":["PI2021\/00679"],"award-info":[{"award-number":["PI2021\/00679"]}]},{"name":"Neurobiology Unit of Institut d\u2019Investigacions Biom\u00e8diques de Barcelona (IIBB\/CSIC)","award":["PI22CIII\/00042"],"award-info":[{"award-number":["PI22CIII\/00042"]}]},{"name":"Neurobiology Unit of Institut d\u2019Investigacions Biom\u00e8diques de Barcelona (IIBB\/CSIC)","award":["S2017\/BMD-3700"],"award-info":[{"award-number":["S2017\/BMD-3700"]}]},{"name":"Neurobiology Unit of Institut d\u2019Investigacions Biom\u00e8diques de Barcelona (IIBB\/CSIC)","award":["NEUROMETAB-CM"],"award-info":[{"award-number":["NEUROMETAB-CM"]}]},{"name":"Neurobiology Unit of Institut d\u2019Investigacions Biom\u00e8diques de Barcelona (IIBB\/CSIC)","award":["CB07\/502"],"award-info":[{"award-number":["CB07\/502"]}]},{"name":"Neurobiology Unit of Institut d\u2019Investigacions Biom\u00e8diques de Barcelona (IIBB\/CSIC)","award":["PI2021\/03"],"award-info":[{"award-number":["PI2021\/03"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes"],"abstract":"<jats:p>Epithelial cells comprising the choroid plexus (CP) form a crucial barrier between the blood and the cerebrospinal fluid, thereby assuming a central position in brain homeostasis and signaling. Mounting evidence suggests that the impairment of CP function may be a significant contributor to Alzheimer\u2019s disease (AD) pathogenesis. CP function relies on the expression of specific receptors, and the potential involvement of olfactory receptors (ORs) and taste receptors (TASRs) in chemical surveillance within the CP is being investigated. Previous studies have implicated ORs and TASRs in neurodegenerative disorders like AD, although the direct evidence of their expression in the human CP remains to be established. In this study, we conducted a transcriptomic analysis encompassing eleven ORs and TASRs in the CP, comparing samples from healthy age-matched controls to those from patients with AD spanning Braak stages I to VI. Among these receptors, a striking finding emerged\u2014OR2K2 exhibited robust expression, with a statistically significant upregulation noted at Braak stage I. Surprisingly, at the protein level, OR2K2 showed a significant decrease in both Braak stage I and VI. Additionally, we identified CP epithelial cells as the source of OR2K2 expression, where it colocalized with autophagy markers LC3 and p62. We postulate that OR2K2 could be subjected to degradation by autophagy in the early stages of AD, triggering a compensatory mechanism that leads to increased OR2K2 mRNA transcription. This study uncovers a potential role for OR2K2 in AD pathogenesis, offering a novel perspective on the intricate dynamics at play in this neurodegenerative disorder.<\/jats:p>","DOI":"10.3390\/genes15030385","type":"journal-article","created":{"date-parts":[[2024,3,21]],"date-time":"2024-03-21T04:34:46Z","timestamp":1710995686000},"page":"385","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Olfactory Receptor OR2K2 Expression in Human Choroid Plexus as a Potential Marker in Early Sporadic Alzheimer\u2019s Disease"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3305-0165","authenticated-orcid":false,"given":"Victoria Cunha","family":"Alves","sequence":"first","affiliation":[{"name":"Neurodegenerative Diseases Group, Hospital Universitario 12 de Octubre Research Institute (imas12), 28041 Madrid, Spain"},{"name":"Network Center for Biomedical Research, Neurodegenerative Diseases (CIBERNED), 28029 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3590-1784","authenticated-orcid":false,"given":"Joana","family":"Figueiro-Silva","sequence":"additional","affiliation":[{"name":"Institute of Medical Genetics, University of Zurich, 8952 Zurich, Switzerland"},{"name":"Department of Molecular Life Science, University of Zurich, 8952 Zurich, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7951-9881","authenticated-orcid":false,"given":"Ramon","family":"Trullas","sequence":"additional","affiliation":[{"name":"Network Center for Biomedical Research, Neurodegenerative Diseases (CIBERNED), 28029 Madrid, Spain"},{"name":"Department of Cell Death and Proliferation, Institut d\u2019Investigacions Biom\u00e8diques de Barcelona, Consejo Superior de Investigaciones Cient\u00edficas (CSIC), Institut d\u2019Investigacions Biom\u00e8diques August Pi I Sunyer (IDIBAPS), 08036 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9888-8754","authenticated-orcid":false,"given":"Isidre","family":"Ferrer","sequence":"additional","affiliation":[{"name":"Network Center for Biomedical Research, Neurodegenerative Diseases (CIBERNED), 28029 Madrid, Spain"},{"name":"Institute of Neuropathology, Bellvitge University Hospital-IDIBELL, 08908 Barcelona, Spain"},{"name":"Department of Pathology and Experimental Therapeutics, University of Barcelona, 08007 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6504-4579","authenticated-orcid":false,"given":"Eva","family":"Carro","sequence":"additional","affiliation":[{"name":"Network Center for Biomedical Research, Neurodegenerative Diseases (CIBERNED), 28029 Madrid, Spain"},{"name":"Neurobiology of Alzheimer\u2019s Disease Unit, Functional Unit for Research into Chronic Diseases, Instituto de Salud Carlos III, 28222 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,3,21]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"445","DOI":"10.1038\/nrn3921","article-title":"Development and functions of the choroid plexus\u2013cerebrospinal fluid system","volume":"16","author":"Lun","year":"2015","journal-title":"Nat. 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Alzheimer\u2019s Dis."}],"container-title":["Genes"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2073-4425\/15\/3\/385\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T14:17:01Z","timestamp":1760105821000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2073-4425\/15\/3\/385"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,3,21]]},"references-count":36,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2024,3]]}},"alternative-id":["genes15030385"],"URL":"https:\/\/doi.org\/10.3390\/genes15030385","relation":{},"ISSN":["2073-4425"],"issn-type":[{"value":"2073-4425","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,3,21]]}}}