{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,2]],"date-time":"2026-06-02T19:55:37Z","timestamp":1780430137873,"version":"3.54.1"},"reference-count":64,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2024,9,16]],"date-time":"2024-09-16T00:00:00Z","timestamp":1726444800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2024,9,16]],"date-time":"2024-09-16T00:00:00Z","timestamp":1726444800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"name":"National Institute on Alcohol Abuse and Alcoholism, United States"},{"DOI":"10.13039\/100000051","name":"National Human Genome Research Institute","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000051","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Virginia Commonwealth University, United States"},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    While previous research has shown the potential links between taste perception pathways and brain-related conditions, the area involving Alzheimer\u2019s disease remains incompletely understood. Taste perception involves neurotransmitter signaling, including serotonin, glutamate, and dopamine. Disruptions in these pathways are implicated in neurodegenerative diseases. The integration of olfactory and taste signals in flavor perception may impact brain health, evident in olfactory dysfunction as an early symptom in neurodegenerative conditions. Shared immune response and inflammatory pathways may contribute to the association between altered taste perception and conditions like neurodegeneration, present in Alzheimer\u2019s disease. This study consists of an exploration of expression-quantitative trait loci (eQTL), utilizing whole-blood transcriptome profiles, of 28 taste perception genes, from a combined cohort of 475 African American subjects. This comprehensive dataset was subsequently intersected with single-nucleotide polymorphisms (SNPs) identified in Genome-Wide Association Studies (GWAS) of Alzheimer\u2019s Disease (AD). Finally, the investigation delved into assessing the association between eQTLs reported in GWAS of AD and the profiles of 741 proteins from the Olink Neurological Panel. The eQTL analysis unveiled 3,547 statistically significant SNP-Gene associations, involving 412 distinct SNPs that spanned all 28 taste genes. In 17 GWAS studies encompassing various traits, a total of 14 SNPs associated with 12 genes were identified, with three SNPs consistently linked to Alzheimer\u2019s disease across four GWAS studies. All three SNPs demonstrated significant associations with the down-regulation of\n                    <jats:italic>TAS2R41,<\/jats:italic>\n                    and two of them were additionally associated with the down-regulation of\n                    <jats:italic>TAS2R60<\/jats:italic>\n                    . In the subsequent pQTL analysis, two of the SNPs linked to\n                    <jats:italic>TAS2R41<\/jats:italic>\n                    and\n                    <jats:italic>TAS2R60<\/jats:italic>\n                    genes (rs117771145 and rs10228407) were correlated with the upregulation of two proteins, namely EPHB6 and ADGRB3. Our investigation introduces a new perspective to the understanding of Alzheimer's disease, emphasizing the significance of bitter taste receptor genes in its pathogenesis. These discoveries set the stage for subsequent research to delve into these receptors as promising avenues for both intervention and diagnosis. Nevertheless, the translation of these genetic insights into clinical practice requires a more profound understanding of the implicated pathways and their pertinence to the disease's progression across diverse populations.\n                  <\/jats:p>","DOI":"10.1038\/s41598-024-71669-9","type":"journal-article","created":{"date-parts":[[2024,9,16]],"date-time":"2024-09-16T04:04:20Z","timestamp":1726459460000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Genomic study of taste perception genes in African Americans reveals SNPs linked to Alzheimer\u2019s disease"],"prefix":"10.1038","volume":"14","author":[{"given":"Paule Valery","family":"Joseph","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Malak","family":"Abbas","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gabriel","family":"Goodney","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ana","family":"Diallo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amadou","family":"Gaye","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2024,9,16]]},"reference":[{"issue":"7117","key":"71669_CR1","doi-asserted-by":"publisher","first-page":"288","DOI":"10.1038\/nature05401","volume":"444","author":"J Chandrashekar","year":"2006","unstructured":"Chandrashekar, J., Hoon, M. A., Ryba, N. J. & Zuker, C. S. The receptors and cells for mammalian taste. Nature 444(7117), 288\u2013294. https:\/\/doi.org\/10.1038\/nature05401 (2006).","journal-title":"Nature"},{"issue":"3\u20134","key":"71669_CR2","doi-asserted-by":"publisher","first-page":"345","DOI":"10.1007\/s00221-005-2376-9","volume":"166","author":"DM Small","year":"2005","unstructured":"Small, D. M. & Prescott, J. Odor\/taste integration and the perception of flavor. Exp. Brain Res. 166(3\u20134), 345\u2013357. https:\/\/doi.org\/10.1007\/s00221-005-2376-9 (2005).","journal-title":"Exp. Brain Res."},{"issue":"2","key":"71669_CR3","doi-asserted-by":"publisher","first-page":"108","DOI":"10.1007\/s13668-019-0269-y","volume":"8","author":"C Kure Liu","year":"2019","unstructured":"Kure Liu, C. et al. Brain imaging of taste perception in obesity: A review. Curr. Nutr. Rep. 8(2), 108\u2013119. https:\/\/doi.org\/10.1007\/s13668-019-0269-y (2019).","journal-title":"Curr. Nutr. Rep."},{"key":"71669_CR4","doi-asserted-by":"publisher","first-page":"255","DOI":"10.1159\/000093764","volume":"63","author":"JG Heckmann","year":"2006","unstructured":"Heckmann, J. G. & Lang, C. J. G. Neurological causes of taste disorders. Adv. Otorhinolaryngol. 63, 255\u2013264. https:\/\/doi.org\/10.1159\/000093764 (2006).","journal-title":"Adv. Otorhinolaryngol."},{"key":"71669_CR5","doi-asserted-by":"crossref","unstructured":"Ram S, Wada T, Sahai-Srivastava S. Neurosensory Disturbances Including Smell and Taste. In: Farah CS, Balasubramaniam R, McCullough MJ, eds. Contemporary Oral Medicine: A Comprehensive Approach to Clinical Practice. Springer International Publishing, (2018)","DOI":"10.1007\/978-3-319-28100-1_26-1"},{"issue":"2","key":"71669_CR6","doi-asserted-by":"publisher","first-page":"234","DOI":"10.1016\/j.cell.2009.10.001","volume":"139","author":"DA Yarmolinsky","year":"2009","unstructured":"Yarmolinsky, D. A., Zuker, C. S. & Ryba, N. J. Common sense about taste: from mammals to insects. Cell 139(2), 234\u2013244. https:\/\/doi.org\/10.1016\/j.cell.2009.10.001 (2009).","journal-title":"Cell"},{"issue":"8","key":"71669_CR7","doi-asserted-by":"publisher","first-page":"776","DOI":"10.1001\/archgenpsychiatry.2012.169","volume":"69","author":"OD Howes","year":"2012","unstructured":"Howes, O. D. et al. The nature of dopamine dysfunction in schizophrenia and what this means for treatment. Arch. Gen. Psychiatry 69(8), 776\u2013786. https:\/\/doi.org\/10.1001\/archgenpsychiatry.2012.169 (2012).","journal-title":"Arch. Gen. Psychiatry"},{"issue":"5","key":"71669_CR8","doi-asserted-by":"publisher","first-page":"305","DOI":"10.1038\/nrn3939","volume":"16","author":"DJ Nutt","year":"2015","unstructured":"Nutt, D. J., Lingford-Hughes, A., Erritzoe, D. & Stokes, P. R. The dopamine theory of addiction: 40 years of highs and lows. Nat. Rev. Neurosci. 16(5), 305\u2013312. https:\/\/doi.org\/10.1038\/nrn3939 (2015).","journal-title":"Nat. Rev. Neurosci."},{"issue":"6","key":"71669_CR9","doi-asserted-by":"publisher","first-page":"478","DOI":"10.1016\/S1474-4422(17)30123-0","volume":"16","author":"RL Doty","year":"2017","unstructured":"Doty, R. L. Olfactory dysfunction in neurodegenerative diseases: Is there a common pathological substrate?. Lancet Neurol. 16(6), 478\u2013488. https:\/\/doi.org\/10.1016\/S1474-4422(17)30123-0 (2017).","journal-title":"Lancet Neurol."},{"key":"71669_CR10","doi-asserted-by":"publisher","first-page":"257","DOI":"10.1016\/s0065-2407(08)60349-3","volume":"13","author":"JE Steiner","year":"1979","unstructured":"Steiner, J. E. Human facial expressions in response to taste and smell stimulation. Adv. Child Dev. Behav. 13, 257\u2013295. https:\/\/doi.org\/10.1016\/s0065-2407(08)60349-3 (1979).","journal-title":"Adv. Child Dev. Behav."},{"issue":"1","key":"71669_CR11","doi-asserted-by":"publisher","first-page":"46","DOI":"10.1038\/nrn2297","volume":"9","author":"R Dantzer","year":"2008","unstructured":"Dantzer, R., O\u2019Connor, J. C., Freund, G. G., Johnson, R. W. & Kelley, K. W. From inflammation to sickness and depression: When the immune system subjugates the brain. Nat. Rev. Neurosci. 9(1), 46\u201356. https:\/\/doi.org\/10.1038\/nrn2297 (2008).","journal-title":"Nat. Rev. Neurosci."},{"issue":"5","key":"71669_CR12","doi-asserted-by":"publisher","first-page":"514","DOI":"10.1111\/j.1755-5949.2010.00177.x","volume":"17","author":"R Medeiros","year":"2011","unstructured":"Medeiros, R., Baglietto-Vargas, D. & LaFerla, F. M. The role of tau in Alzheimer\u2019s disease and related disorders. CNS Neurosci. Ther. 17(5), 514\u2013524. https:\/\/doi.org\/10.1111\/j.1755-5949.2010.00177.x (2011).","journal-title":"CNS Neurosci. Ther."},{"issue":"3","key":"71669_CR13","doi-asserted-by":"publisher","first-page":"395","DOI":"10.1159\/000481854","volume":"7","author":"M Sakai","year":"2017","unstructured":"Sakai, M. et al. Gustatory Dysfunction as an Early Symptom of Semantic Dementia. Dement. Geriatr. Cogn. Dis. Extra. 7(3), 395\u2013405. https:\/\/doi.org\/10.1159\/000481854 (2017).","journal-title":"Dement. Geriatr. Cogn. Dis. Extra."},{"issue":"3","key":"71669_CR14","doi-asserted-by":"publisher","first-page":"511","DOI":"10.1017\/s1041610215001337","volume":"28","author":"M Sakai","year":"2016","unstructured":"Sakai, M., Ikeda, M., Kazui, H., Shigenobu, K. & Nishikawa, T. Decline of gustatory sensitivity with the progression of Alzheimer\u2019s disease. Int. Psychogeriatr. 28(3), 511\u2013517. https:\/\/doi.org\/10.1017\/s1041610215001337 (2016).","journal-title":"Int. Psychogeriatr."},{"key":"71669_CR15","doi-asserted-by":"publisher","DOI":"10.1016\/S0197-4580(01)00337-2","author":"SS Schiffman","year":"2002","unstructured":"Schiffman, S. S., Graham, B. G., Sattely-Miller, E. A., Zervakis, J. & Welsh-Bohmer, K. Taste, smell and neuropsychological performance of individuals at familial risk for Alzheimer\u2019s disease. Neurobiol. Aging https:\/\/doi.org\/10.1016\/S0197-4580(01)00337-2 (2002).","journal-title":"Neurobiol. Aging"},{"issue":"2","key":"71669_CR16","doi-asserted-by":"publisher","first-page":"238","DOI":"10.1007\/s00415-009-5300-6","volume":"257","author":"S Steinbach","year":"2010","unstructured":"Steinbach, S. et al. Taste in mild cognitive impairment and Alzheimer\u2019s disease. J. Neurol. 257(2), 238\u2013246. https:\/\/doi.org\/10.1007\/s00415-009-5300-6 (2010).","journal-title":"J. Neurol."},{"issue":"12","key":"71669_CR17","doi-asserted-by":"publisher","first-page":"1452","DOI":"10.1038\/ng.2802","volume":"45","author":"JC Lambert","year":"2013","unstructured":"Lambert, J. C. et al. Meta-analysis of 74,046 individuals identifies 11 new susceptibility loci for Alzheimer\u2019s disease. Nat. Genet. 45(12), 1452\u20131458. https:\/\/doi.org\/10.1038\/ng.2802 (2013).","journal-title":"Nat. Genet."},{"key":"71669_CR18","doi-asserted-by":"publisher","DOI":"10.1038\/s41398-018-0150-6","author":"RE Marioni","year":"2018","unstructured":"Marioni, R. E. et al. GWAS on family history of Alzheimer\u2019s disease. Transl. Psychiatry https:\/\/doi.org\/10.1038\/s41398-018-0150-6 (2018).","journal-title":"Transl. Psychiatry"},{"issue":"10","key":"71669_CR19","doi-asserted-by":"publisher","first-page":"1333","DOI":"10.1016\/j.jalz.2019.06.4950","volume":"15","author":"S Moreno-Grau","year":"2019","unstructured":"Moreno-Grau, S. et al. Genome-wide association analysis of dementia and its clinical endophenotypes reveal novel loci associated with Alzheimer\u2019s disease and three causality networks: The GR@ACE project. Alzheimers Dement. 15(10), 1333\u20131347. https:\/\/doi.org\/10.1016\/j.jalz.2019.06.4950 (2019).","journal-title":"Alzheimers Dement."},{"issue":"4","key":"71669_CR20","doi-asserted-by":"publisher","first-page":"412","DOI":"10.1038\/s41588-022-01024-z","volume":"54","author":"C Bellenguez","year":"2022","unstructured":"Bellenguez, C. et al. New insights into the genetic etiology of Alzheimer\u2019s disease and related dementias. Nat Genet. 54(4), 412\u2013436. https:\/\/doi.org\/10.1038\/s41588-022-01024-z (2022).","journal-title":"Nat Genet."},{"issue":"3","key":"71669_CR21","doi-asserted-by":"publisher","first-page":"404","DOI":"10.1038\/s41588-018-0311-9","volume":"51","author":"IE Jansen","year":"2019","unstructured":"Jansen, I. E. et al. Genome-wide meta-analysis identifies new loci and functional pathways influencing Alzheimer\u2019s disease risk. Nat Genet. 51(3), 404\u2013413. https:\/\/doi.org\/10.1038\/s41588-018-0311-9 (2019).","journal-title":"Nat Genet."},{"issue":"8","key":"71669_CR22","doi-asserted-by":"publisher","first-page":"1461","DOI":"10.1002\/alz.12509","volume":"18","author":"JC Lennon","year":"2022","unstructured":"Lennon, J. C. et al. Black and White individuals differ in dementia prevalence, risk factors, and symptomatic presentation. Alzheimers Dement. 18(8), 1461\u20131471. https:\/\/doi.org\/10.1002\/alz.12509 (2022).","journal-title":"Alzheimers Dement."},{"key":"71669_CR23","unstructured":"Association As. Black Americans and alzheimer's. https:\/\/www.alz.org\/help-support\/resources\/black-americans-and-alzheimers, (Accessed 02 May 2024)."},{"key":"71669_CR24","unstructured":"Institute B. broadinstitute\/gtex-pipeline. https:\/\/github.com\/broadinstitute\/gtex-pipeline"},{"issue":"3","key":"71669_CR25","doi-asserted-by":"publisher","first-page":"R25","DOI":"10.1186\/gb-2010-11-3-r25","volume":"11","author":"MD Robinson","year":"2010","unstructured":"Robinson, M. D. & Oshlack, A. A scaling normalization method for differential expression analysis of RNA-seq data. Genome Biol. 11(3), R25. https:\/\/doi.org\/10.1186\/gb-2010-11-3-r25 (2010).","journal-title":"Genome Biol."},{"issue":"D1","key":"71669_CR26","doi-asserted-by":"publisher","first-page":"D977","DOI":"10.1093\/nar\/gkac1010","volume":"51","author":"E Sollis","year":"2023","unstructured":"Sollis, E. et al. The NHGRI-EBI GWAS Catalog: knowledgebase and deposition resource. Nucleic Acids Res. 51(D1), D977\u2013D985. https:\/\/doi.org\/10.1093\/nar\/gkac1010 (2023).","journal-title":"Nucleic Acids Res."},{"issue":"10","key":"71669_CR27","doi-asserted-by":"publisher","first-page":"1353","DOI":"10.1093\/bioinformatics\/bts163","volume":"28","author":"AA Shabalin","year":"2012","unstructured":"Shabalin, A. A. Matrix eQTL: Ultra fast eQTL analysis via large matrix operations. Bioinformatics 28(10), 1353\u20131358. https:\/\/doi.org\/10.1093\/bioinformatics\/bts163 (2012).","journal-title":"Bioinformatics"},{"issue":"4","key":"71669_CR28","doi-asserted-by":"publisher","first-page":"407","DOI":"10.1111\/apha.12621","volume":"216","author":"B Avau","year":"2016","unstructured":"Avau, B. & Depoortere, I. The bitter truth about bitter taste receptors: beyond sensing bitter in the oral cavity. Acta Physiol. (Oxf). 216(4), 407\u2013420. https:\/\/doi.org\/10.1111\/apha.12621 (2016).","journal-title":"Acta Physiol. (Oxf)."},{"key":"71669_CR29","doi-asserted-by":"publisher","DOI":"10.3390\/nu11092017","author":"RM Carey","year":"2019","unstructured":"Carey, R. M. & Lee, R. J. Taste receptors in upper airway innate immunity. Nutrients https:\/\/doi.org\/10.3390\/nu11092017 (2019).","journal-title":"Nutrients"},{"key":"71669_CR30","doi-asserted-by":"publisher","DOI":"10.1016\/j.bcp.2020.113954","author":"AC Duarte","year":"2020","unstructured":"Duarte, A. C. et al. Bitter taste receptors profiling in the human blood-cerebrospinal fluid-barrier. Biochem. Pharmacol. https:\/\/doi.org\/10.1016\/j.bcp.2020.113954 (2020).","journal-title":"Biochem. Pharmacol."},{"key":"71669_CR31","doi-asserted-by":"publisher","DOI":"10.1016\/j.bcp.2022.114915","author":"AC Duarte","year":"2022","unstructured":"Duarte, A. C. et al. The druggability of bitter taste receptors for the treatment of neurodegenerative disorders. Biochem. Pharmacol. https:\/\/doi.org\/10.1016\/j.bcp.2022.114915 (2022).","journal-title":"Biochem. Pharmacol."},{"issue":"2","key":"71669_CR32","doi-asserted-by":"publisher","first-page":"181","DOI":"10.1085\/jgp.201611637","volume":"149","author":"P Lu","year":"2017","unstructured":"Lu, P., Zhang, C. H., Lifshitz, L. M. & ZhuGe, R. Extraoral bitter taste receptors in health and disease. J. Gen. Physiol. 149(2), 181\u2013197. https:\/\/doi.org\/10.1085\/jgp.201611637 (2017).","journal-title":"J. Gen. Physiol."},{"key":"71669_CR33","doi-asserted-by":"publisher","DOI":"10.3390\/ijms24010081","author":"VC de Jesus","year":"2022","unstructured":"de Jesus, V. C., Mittermuller, B. A., Hu, P., Schroth, R. J. & Chelikani, P. Association between downstream taste signaling genes, oral microbiome, and severe early childhood caries. Int. J. Mol. Sci. https:\/\/doi.org\/10.3390\/ijms24010081 (2022).","journal-title":"Int. J. Mol. Sci."},{"key":"71669_CR34","doi-asserted-by":"publisher","first-page":"70","DOI":"10.1016\/j.cophys.2021.01.006","volume":"20","author":"CP Harmon","year":"2021","unstructured":"Harmon, C. P., Deng, D. & Breslin, P. A. S. Bitter taste receptors (T2Rs) are sentinels that coordinate metabolic and immunological defense responses. Curr. Opin. Physiol. 20, 70\u201376. https:\/\/doi.org\/10.1016\/j.cophys.2021.01.006 (2021).","journal-title":"Curr. Opin. Physiol."},{"key":"71669_CR35","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2164-15-1057","author":"EC da Silva","year":"2014","unstructured":"da Silva, E. C. et al. Characterization of the porcine nutrient and taste receptor gene repertoire in domestic and wild populations across the globe. BMC Genomics. https:\/\/doi.org\/10.1186\/1471-2164-15-1057 (2014).","journal-title":"BMC Genomics."},{"issue":"1","key":"71669_CR36","doi-asserted-by":"publisher","first-page":"4","DOI":"10.1016\/j.physbeh.2011.02.010","volume":"105","author":"M Behrens","year":"2011","unstructured":"Behrens, M. & Meyerhof, W. Gustatory and extragustatory functions of mammalian taste receptors. Physiol. Behav. 105(1), 4\u201313. https:\/\/doi.org\/10.1016\/j.physbeh.2011.02.010 (2011).","journal-title":"Physiol. Behav."},{"issue":"7","key":"71669_CR37","doi-asserted-by":"publisher","first-page":"759","DOI":"10.1177\/00220345221077989","volume":"101","author":"R Xi","year":"2022","unstructured":"Xi, R., Zheng, X. & Tizzano, M. Role of taste receptors in innate immunity and oral health. J. Dent. Res. 101(7), 759\u2013768. https:\/\/doi.org\/10.1177\/00220345221077989 (2022).","journal-title":"J. Dent. Res."},{"issue":"1","key":"71669_CR38","doi-asserted-by":"publisher","first-page":"89","DOI":"10.1007\/s10787-022-01086-9","volume":"31","author":"MO Welcome","year":"2023","unstructured":"Welcome, M. O., Dogo, D. & Nikos, E. M. Cellular mechanisms and molecular pathways linking bitter taste receptor signalling to cardiac inflammation, oxidative stress, arrhythmia and contractile dysfunction in heart diseases. Inflammopharmacology 31(1), 89\u2013117. https:\/\/doi.org\/10.1007\/s10787-022-01086-9 (2023).","journal-title":"Inflammopharmacology"},{"key":"71669_CR39","doi-asserted-by":"publisher","DOI":"10.1016\/j.phrs.2021.105557","author":"MO Welcome","year":"2021","unstructured":"Welcome, M. O. & Mastorakis, N. E. The taste of neuroinflammation: Molecular mechanisms linking taste sensing to neuroinflammatory responses. Pharmacol. Res. https:\/\/doi.org\/10.1016\/j.phrs.2021.105557 (2021).","journal-title":"Pharmacol. Res."},{"key":"71669_CR40","doi-asserted-by":"publisher","first-page":"1008","DOI":"10.3389\/fphar.2019.01008","volume":"10","author":"L Guzman-Martinez","year":"2019","unstructured":"Guzman-Martinez, L. et al. Neuroinflammation as a Common Feature of Neurodegenerative Disorders. Front. Pharmacol. 10, 1008. https:\/\/doi.org\/10.3389\/fphar.2019.01008 (2019).","journal-title":"Front. Pharmacol."},{"key":"71669_CR41","doi-asserted-by":"publisher","DOI":"10.1186\/s12967-021-03067-y","author":"K Tuzim","year":"2021","unstructured":"Tuzim, K. & Korolczuk, A. An update on extra-oral bitter taste receptors. J. Transl. Med. https:\/\/doi.org\/10.1186\/s12967-021-03067-y (2021).","journal-title":"J. Transl. Med."},{"key":"71669_CR42","doi-asserted-by":"publisher","DOI":"10.21203\/rs.3.rs-3304297\/v1","author":"G Dong","year":"2023","unstructured":"Dong, G., Boothe, K., He, L., Shi, Y. & McCluskey, L. P. Altered peripheral taste function in a mouse model of inflammatory bowel disease. Res. Sq. https:\/\/doi.org\/10.21203\/rs.3.rs-3304297\/v1 (2023).","journal-title":"Res. Sq."},{"key":"71669_CR43","doi-asserted-by":"publisher","DOI":"10.1038\/sigtrans.2017.23","author":"T Liu","year":"2017","unstructured":"Liu, T., Zhang, L., Joo, D. & Sun, S. C. NF-kappaB signaling in inflammation. Signal Transduct. Target Ther. https:\/\/doi.org\/10.1038\/sigtrans.2017.23 (2017).","journal-title":"Signal Transduct. Target Ther."},{"key":"71669_CR44","doi-asserted-by":"publisher","first-page":"575","DOI":"10.1016\/j.trci.2018.06.014","volume":"4","author":"JW Kinney","year":"2018","unstructured":"Kinney, J. W. et al. Inflammation as a central mechanism in Alzheimer\u2019s disease. Alzheimers Dement (N Y). 4, 575\u2013590. https:\/\/doi.org\/10.1016\/j.trci.2018.06.014 (2018).","journal-title":"Alzheimers Dement (N Y)."},{"key":"71669_CR45","doi-asserted-by":"publisher","DOI":"10.3389\/fgene.2022.952299","author":"SP Wooding","year":"2022","unstructured":"Wooding, S. P. & Ramirez, V. A. Global population genetics and diversity in the TAS2R bitter taste receptor family. Front. Genet. https:\/\/doi.org\/10.3389\/fgene.2022.952299 (2022).","journal-title":"Front. Genet."},{"issue":"4","key":"71669_CR46","doi-asserted-by":"publisher","first-page":"240","DOI":"10.1038\/nrm.2015.16","volume":"17","author":"A Kania","year":"2016","unstructured":"Kania, A. & Klein, R. Mechanisms of ephrin-Eph signalling in development, physiology and disease. Nat. Rev. Mol. Cell Biol. 17(4), 240\u2013256. https:\/\/doi.org\/10.1038\/nrm.2015.16 (2016).","journal-title":"Nat. Rev. Mol. Cell Biol."},{"issue":"1","key":"71669_CR47","doi-asserted-by":"publisher","first-page":"75","DOI":"10.1016\/j.semcdb.2011.10.020","volume":"23","author":"S Sloniowski","year":"2012","unstructured":"Sloniowski, S. & Ethell, I. M. Looking forward to EphB signaling in synapses. Semin Cell Dev. Biol. 23(1), 75\u201382. https:\/\/doi.org\/10.1016\/j.semcdb.2011.10.020 (2012).","journal-title":"Semin Cell Dev. Biol."},{"key":"71669_CR48","doi-asserted-by":"publisher","DOI":"10.1038\/s41419-023-05825-w","author":"CH He","year":"2023","unstructured":"He, C. H. et al. Overexpression of EphB6 and EphrinB2 controls soma spacing of cortical neurons in a mutual inhibitory way. Cell Death Dis. https:\/\/doi.org\/10.1038\/s41419-023-05825-w (2023).","journal-title":"Cell Death Dis."},{"key":"71669_CR49","doi-asserted-by":"publisher","first-page":"1473","DOI":"10.3389\/fimmu.2019.01473","volume":"10","author":"TK Darling","year":"2019","unstructured":"Darling, T. K. & Lamb, T. J. Emerging roles for eph receptors and ephrin ligands in immunity. Front Immunol. 10, 1473. https:\/\/doi.org\/10.3389\/fimmu.2019.01473 (2019).","journal-title":"Front Immunol."},{"key":"71669_CR50","doi-asserted-by":"publisher","first-page":"1282","DOI":"10.3389\/fphar.2019.01282","volume":"10","author":"I Dal Pra","year":"2019","unstructured":"Dal Pra, I., Armato, U. & Chiarini, A. Family C G-protein-coupled receptors in Alzheimer\u2019s disease and therapeutic implications. Front Pharmacol. 10, 1282. https:\/\/doi.org\/10.3389\/fphar.2019.01282 (2019).","journal-title":"Front Pharmacol."},{"key":"71669_CR51","doi-asserted-by":"publisher","DOI":"10.1038\/mp.2013.46","author":"V Lanoue","year":"2013","unstructured":"Lanoue, V. et al. The adhesion-GPCR BAI3, a gene linked to psychiatric disorders, regulates dendrite morphogenesis in neurons. Mol. Psychiatry https:\/\/doi.org\/10.1038\/mp.2013.46 (2013).","journal-title":"Mol. Psychiatry"},{"issue":"31","key":"71669_CR52","doi-asserted-by":"publisher","first-page":"22248","DOI":"10.1074\/jbc.M113.489757","volume":"288","author":"JR Stephenson","year":"2013","unstructured":"Stephenson, J. R. et al. Brain-specific angiogenesis inhibitor-1 signaling, regulation, and enrichment in the postsynaptic density. J. Biol. Chem. 288(31), 22248\u201322256. https:\/\/doi.org\/10.1074\/jbc.M113.489757 (2013).","journal-title":"J. Biol. Chem."},{"key":"71669_CR53","doi-asserted-by":"publisher","DOI":"10.1016\/j.expneurol.2022.113994","volume":"351","author":"FH Shiu","year":"2022","unstructured":"Shiu, F. H. et al. Mice lacking full length Adgrb1 (Bai1) exhibit social deficits, increased seizure susceptibility, and altered brain development. Exp. Neurol. 351, 113994. https:\/\/doi.org\/10.1016\/j.expneurol.2022.113994 (2022).","journal-title":"Exp. Neurol."},{"issue":"7","key":"71669_CR54","doi-asserted-by":"publisher","first-page":"493","DOI":"10.1089\/omi.2018.0047","volume":"22","author":"JS Choi","year":"2018","unstructured":"Choi, J. S., Bae, W. Y., Nam, S. & Jeong, J. W. New targets for Parkinson\u2019s disease: Adhesion G protein-coupled receptor B1 is downregulated by AMP-activated protein kinase activation. OMICS 22(7), 493\u2013501. https:\/\/doi.org\/10.1089\/omi.2018.0047 (2018).","journal-title":"OMICS"},{"issue":"1","key":"71669_CR55","doi-asserted-by":"publisher","first-page":"147","DOI":"10.1016\/j.bbrc.2009.11.022","volume":"391","author":"JS Choi","year":"2010","unstructured":"Choi, J. S., Park, C. & Jeong, J. W. AMP-activated protein kinase is activated in Parkinson\u2019s disease models mediated by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine. Biochem. Biophys. Res. Commun. 391(1), 147\u2013151. https:\/\/doi.org\/10.1016\/j.bbrc.2009.11.022 (2010).","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"71669_CR56","doi-asserted-by":"publisher","first-page":"429","DOI":"10.1146\/annurev-pharmtox-010617-052933","volume":"58","author":"RH Purcell","year":"2018","unstructured":"Purcell, R. H. & Hall, R. A. Adhesion G protein-coupled receptors as drug targets. Annu. Rev. Pharmacol. Toxicol. 58, 429\u2013449. https:\/\/doi.org\/10.1146\/annurev-pharmtox-010617-052933 (2018).","journal-title":"Annu. Rev. Pharmacol. Toxicol."},{"issue":"4","key":"71669_CR57","doi-asserted-by":"publisher","first-page":"1587","DOI":"10.1152\/physrev.00027.2021","volume":"102","author":"T Lala","year":"2022","unstructured":"Lala, T. & Hall, R. A. Adhesion G protein-coupled receptors: Structure, signaling, physiology, and pathophysiology. Physiol. Rev. 102(4), 1587\u20131624. https:\/\/doi.org\/10.1152\/physrev.00027.2021 (2022).","journal-title":"Physiol. Rev."},{"issue":"4","key":"71669_CR58","doi-asserted-by":"publisher","first-page":"594","DOI":"10.1038\/s41431-018-0321-1","volume":"27","author":"C Scuderi","year":"2019","unstructured":"Scuderi, C. et al. Biallelic intragenic duplication in ADGRB3 (BAI3) gene associated with intellectual disability, cerebellar atrophy, and behavioral disorder. Eur. J. Hum. Genet. 27(4), 594\u2013602. https:\/\/doi.org\/10.1038\/s41431-018-0321-1 (2019).","journal-title":"Eur. J. Hum. Genet."},{"key":"71669_CR59","doi-asserted-by":"publisher","unstructured":"Bipolar D, Schizophrenia Working Group of the Psychiatric Genomics Consortium. Electronic address drve, Bipolar D, Schizophrenia Working Group of the Psychiatric Genomics C. Genomic Dissection of Bipolar Disorder and Schizophrenia, Including 28 Subphenotypes. Cell. https:\/\/doi.org\/10.1016\/j.cell.2018.05.046, (2018).","DOI":"10.1016\/j.cell.2018.05.046"},{"key":"71669_CR60","doi-asserted-by":"publisher","unstructured":"Zehentner S, Reiner AT, Grimm C, Somoza V. The Role of Bitter Taste Receptors in Cancer: A Systematic Review. Cancers (Basel). Nov 23 2021;13(23)https:\/\/doi.org\/10.3390\/cancers13235891","DOI":"10.3390\/cancers13235891"},{"key":"71669_CR61","doi-asserted-by":"publisher","first-page":"6038996","DOI":"10.1155\/2022\/6038996","volume":"2022","author":"T Minocha","year":"2022","unstructured":"Minocha, T. et al. Flavonoids as promising neuroprotectants and their therapeutic potential against Alzheimer\u2019s disease. Oxid. Med. Cell. Longev. 2022, 6038996. https:\/\/doi.org\/10.1155\/2022\/6038996 (2022).","journal-title":"Oxid. Med. Cell. Longev."},{"key":"71669_CR62","doi-asserted-by":"publisher","DOI":"10.1007\/s11882-019-0876-0","author":"AP Nayak","year":"2019","unstructured":"Nayak, A. P., Villalba, D. & Deshpande, D. A. Bitter taste receptors: An answer to comprehensive asthma control?. Curr. Allergy Asthma. Rep. https:\/\/doi.org\/10.1007\/s11882-019-0876-0 (2019).","journal-title":"Curr. Allergy Asthma. Rep."},{"key":"71669_CR63","doi-asserted-by":"publisher","DOI":"10.1186\/s13024-022-00592-2","author":"SR Oatman","year":"2023","unstructured":"Oatman, S. R. et al. Genome-wide association study of brain biochemical phenotypes reveals distinct genetic architecture of Alzheimer\u2019s disease related proteins. Mol. Neurodegener. https:\/\/doi.org\/10.1186\/s13024-022-00592-2 (2023).","journal-title":"Mol. Neurodegener."},{"issue":"2","key":"71669_CR64","doi-asserted-by":"publisher","first-page":"223","DOI":"10.1177\/1099800420947176","volume":"23","author":"RR Romano 3rd","year":"2021","unstructured":"Romano, R. R. 3rd., Carter, M. A. & Monroe, T. B. Narrative review of sensory changes as a biomarker for Alzheimer\u2019s disease. Biol Res Nurs. 23(2), 223\u2013230. https:\/\/doi.org\/10.1177\/1099800420947176 (2021).","journal-title":"Biol Res Nurs."}],"container-title":["Scientific Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41598-024-71669-9.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-024-71669-9","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-024-71669-9.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,9,20]],"date-time":"2024-09-20T11:07:21Z","timestamp":1726830441000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41598-024-71669-9"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,9,16]]},"references-count":64,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2024,12]]}},"alternative-id":["71669"],"URL":"https:\/\/doi.org\/10.1038\/s41598-024-71669-9","relation":{"has-preprint":[{"id-type":"doi","id":"10.1101\/2024.08.10.607452","asserted-by":"object"}]},"ISSN":["2045-2322"],"issn-type":[{"value":"2045-2322","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,9,16]]},"assertion":[{"value":"5 March 2024","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"29 August 2024","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"16 September 2024","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare no competing interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}},{"value":"This study was approved by National Institutes of Health Institutional Review Board (IRB). The study was conducted in accordance with the local legislation and institutional requirements. The participants provided their written informed consent to participate.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to particpate"}}],"article-number":"21560"}}