{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,11]],"date-time":"2026-07-11T02:25:15Z","timestamp":1783736715649,"version":"3.55.0"},"reference-count":61,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2019,9,1]],"date-time":"2019-09-01T00:00:00Z","timestamp":1567296000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100012553","name":"Chang Gung Memorial Hospital","doi-asserted-by":"publisher","award":["CMRPG3F1091"],"award-info":[{"award-number":["CMRPG3F1091"]}],"id":[{"id":"10.13039\/100012553","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100012553","name":"Chang Gung Memorial Hospital","doi-asserted-by":"publisher","award":["CFRPG6J0051"],"award-info":[{"award-number":["CFRPG6J0051"]}],"id":[{"id":"10.13039\/100012553","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004663","name":"Ministry of Science and Technology, Taiwan","doi-asserted-by":"publisher","award":["NSC102-2314-B-182A-082"],"award-info":[{"award-number":["NSC102-2314-B-182A-082"]}],"id":[{"id":"10.13039\/501100004663","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCM"],"abstract":"<jats:p>Background: Obstructive sleep apnea (OSA) increases the risk of Alzheimer\u2019s disease (AD), and inflammation may be involved in the early pathogenesis of AD in patients with OSA. However, the potential pathways between OSA and AD have yet to be established. In this study, we aimed to investigate differential expressions of AD-associated genes in OSA patients without evident AD or dementia. Methods: This prospective case-control study included five patients with severe OSA and five age and sex-matched patients with non-severe OSA without evident dementia who underwent uvulopalatopharyngoplasty between 1 January 2013 and 31 December 2015. The expressions of genes associated with AD were analyzed using whole-exome sequencing. Unsupervised two-dimensional hierarchical clustering was performed on these genes. Pearson\u2019s correlation was used as the distance metric to simultaneously cluster subjects and genes. Results: The expressions of CCL2, IL6, CXCL8, HLA-A, and IL1RN in the patients with severe OSA were significantly different from those in the patients with non-severe OSA and contributed to changes in the immune response, cytokine\u2013cytokine receptor interactions, and nucleotide-binding oligomerization domain-like receptor signaling pathways. Conclusions: Inflammation may contribute to the onset of AD and physicians need to be aware of the potential occurrence of AD in patients with severe OSA.<\/jats:p>","DOI":"10.3390\/jcm8091361","type":"journal-article","created":{"date-parts":[[2019,9,2]],"date-time":"2019-09-02T03:16:12Z","timestamp":1567394172000},"page":"1361","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Alterations in Alzheimer\u2019s Disease-Associated Gene Expression in Severe Obstructive Sleep Apnea Patients"],"prefix":"10.3390","volume":"8","author":[{"given":"Hsueh-Yu","family":"Li","sequence":"first","affiliation":[{"name":"Department of Otolaryngology\u2014Head and Neck Surgery, Linkou Chang Gung Memorial Hospital, Taoyuan 333, Taiwan"},{"name":"Faculty of Medicine, College of Medicine, Chang Gung University, Taoyuan 333, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9314-5940","authenticated-orcid":false,"given":"Ming-Shao","family":"Tsai","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, College of Medicine, Chang Gung University, Taoyuan 333, Taiwan"},{"name":"Department of Otolaryngology\u2014Head and Neck Surgery, Chiayi Chang Gung Memorial Hospital, Chiayi 613, Taiwan"},{"name":"Graduate Institute of Clinical Medical Sciences, College of Medicine, Chang Gung University, Taoyuan 333, Taiwan"},{"name":"Health Information and Epidemiology Laboratory, Chiayi, Chang Gung Memorial Hospital, Chiayi 613, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chung-Guei","family":"Huang","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine, Linkou Chang Gung Memorial Hospital, Taoyuan 333, Taiwan"},{"name":"Research Center for Emerging Viral Infections, Chang Gung University, Taoyuan 333, Taiwan"},{"name":"Graduate Institute of Biomedical Sciences, Department of Medical Biotechnology and Laboratory Science, College of Medicine, Chang Gung University, Taoyuan 333, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1322-3890","authenticated-orcid":false,"given":"Robert","family":"Wang","sequence":"additional","affiliation":[{"name":"Research Center for Emerging Viral Infections, Chang Gung University, Taoyuan 333, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5466-8995","authenticated-orcid":false,"given":"Li-Pang","family":"Chuang","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, College of Medicine, Chang Gung University, Taoyuan 333, Taiwan"},{"name":"Graduate Institute of Clinical Medical Sciences, College of Medicine, Chang Gung University, Taoyuan 333, Taiwan"},{"name":"Department of Pulmonary and Critical Care Medicine, Taoyuan Chang Gung Memorial Hospital, Taoyuan 333, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ning-Hung","family":"Chen","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, College of Medicine, Chang Gung University, Taoyuan 333, Taiwan"},{"name":"Department of Pulmonary and Critical Care Medicine, Taoyuan Chang Gung Memorial Hospital, Taoyuan 333, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chi-Hung","family":"Liu","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, College of Medicine, Chang Gung University, Taoyuan 333, Taiwan"},{"name":"Graduate Institute of Clinical Medical Sciences, College of Medicine, Chang Gung University, Taoyuan 333, Taiwan"},{"name":"Stroke Center and Department of Neurology, Linkou Chang Gung Memorial Hospital, Taoyuan 333, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3792-3784","authenticated-orcid":false,"given":"Cheng-Ming","family":"Hsu","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology\u2014Head and Neck Surgery, Chiayi Chang Gung Memorial Hospital, Chiayi 613, Taiwan"},{"name":"School of Traditional Chinese Medicine, College of Medicine, Chang Gung University, Taoyuan 333, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wen-Nuan","family":"Cheng","sequence":"additional","affiliation":[{"name":"Department of Sports Sciences, University of Taipei, Taipei 111, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8414-595X","authenticated-orcid":false,"given":"Li-Ang","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology\u2014Head and Neck Surgery, Linkou Chang Gung Memorial Hospital, Taoyuan 333, Taiwan"},{"name":"Faculty of Medicine, College of Medicine, Chang Gung University, Taoyuan 333, Taiwan"},{"name":"Graduate Institute of Clinical Medical Sciences, College of Medicine, Chang Gung University, Taoyuan 333, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2019,9,1]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"404","DOI":"10.1016\/S2213-2600(15)00090-9","article-title":"Sleep apnoea and the brain: A complex relationship","volume":"3","author":"Rosenzweig","year":"2015","journal-title":"Lancet Respir. Med."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"656","DOI":"10.1016\/j.neubiorev.2014.10.019","article-title":"Can sleep apnea cause Alzheimer\u2019s disease?","volume":"47","author":"Pan","year":"2014","journal-title":"Neurosci. Biobehav. Rev."},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Chang, W.P., Liu, M.E., Chang, W.C., Yang, A.C., Ku, Y.C., Pai, J.T., Huang, H.L., and Tsai, S.J. (2013). Sleep apnea and the risk of dementia: A population-based 5-year follow-up study in Taiwan. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0078655"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"624","DOI":"10.1016\/j.psychres.2019.01.086","article-title":"Sleep-disordered breathing and Alzheimer\u2019s disease: A nationwide cohort study","volume":"273","author":"Lee","year":"2019","journal-title":"Psychiatry Res."},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Bubu, O.M., Brannick, M., Mortimer, J., Umasabor-Bubu, O., Sebastiao, Y.V., Wen, Y., Schwartz, S., Borenstein, A.R., Wu, Y., and Morgan, D. (2017). Sleep, Cognitive impairment, and Alzheimer\u2019s disease: A Systematic Review and Meta-Analysis. Sleep, 40.","DOI":"10.1093\/sleep\/zsw032"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"4","DOI":"10.1016\/j.smrv.2017.06.010","article-title":"Sleep disturbances increase the risk of dementia: A systematic review and meta-analysis","volume":"40","author":"Shi","year":"2018","journal-title":"Sleep Med. Rev."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"993","DOI":"10.3233\/JAD-161287","article-title":"Is Sleep Disruption a Risk Factor for Alzheimer\u2019s Disease?","volume":"58","author":"Macedo","year":"2017","journal-title":"J. Alzheimer\u2019s Dis."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"89","DOI":"10.3389\/fncel.2014.00089","article-title":"Emerging bioinformatics approaches for analysis of NGS-derived coding and non-coding RNAs in neurodegenerative diseases","volume":"8","author":"Guffanti","year":"2014","journal-title":"Front. Cell. Neurosci."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"550","DOI":"10.1038\/nature12825","article-title":"Rare coding variants in the phospholipase D3 gene confer risk for Alzheimer\u2019s disease","volume":"505","author":"Cruchaga","year":"2014","journal-title":"Nature"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"74","DOI":"10.1016\/j.ejphar.2013.10.070","article-title":"FK506-binding protein 1b\/12.6: A key to aging-related hippocampal Ca2+ dysregulation?","volume":"739","author":"Gant","year":"2014","journal-title":"Eur. J. Pharmacol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"319","DOI":"10.3389\/fnmol.2017.00319","article-title":"Alzheimer\u2019s Disease: From Genetic Variants to the Distinct Pathological Mechanisms","volume":"10","author":"Sun","year":"2017","journal-title":"Front. Mol. Neurosci."},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Alzheimer\u2019s Association (2015). 2015 Alzheimer\u2019s disease facts and figures. Alzheimer\u2019s Dement., 11, 332\u2013384.","DOI":"10.1016\/j.jalz.2015.02.003"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"429","DOI":"10.1038\/ng.803","article-title":"Common variants at ABCA7, MS4A6A\/MS4A4E, EPHA1, CD33 and CD2AP are associated with Alzheimer\u2019s disease","volume":"43","author":"Hollingworth","year":"2011","journal-title":"Nat. Genet."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"180","DOI":"10.1016\/j.neulet.2007.02.010","article-title":"ABCA1 polymorphisms and Alzheimer\u2019s disease","volume":"416","author":"Compton","year":"2007","journal-title":"Neurosci. Lett."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"6476","DOI":"10.1007\/s12035-015-9547-x","article-title":"Association of Single-Nucleotide Polymorphism in ANK1 with Late-Onset Alzheimer\u2019s Disease in Han Chinese","volume":"53","author":"Chi","year":"2016","journal-title":"Mol. Neurobiol."},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Patel, T., Brookes, K.J., Turton, J., Chaudhury, S., Guetta-Baranes, T., Guerreiro, R., Bras, J., Hernandez, D., Singleton, A., and Francis, P.T. (2017). Whole-exome sequencing of the BDR cohort: evidence to support the role of the PILRA gene in Alzheimer\u2019s disease. Neuropathol. Appl. Neurobiol.","DOI":"10.1111\/nan.12452"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"106","DOI":"10.1038\/nrneurol.2012.263","article-title":"Apolipoprotein E and Alzheimer disease: Risk, mechanisms and therapy","volume":"9","author":"Liu","year":"2013","journal-title":"Nat. Rev. Neurol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"189","DOI":"10.1016\/j.neulet.2016.01.059","article-title":"Meta-analysis of BACE1 gene rs638405 polymorphism and the risk of Alzheimer\u2019s disease in Caucasion and Asian population","volume":"616","author":"Yu","year":"2016","journal-title":"Neurosci. Lett."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1832","DOI":"10.1001\/jama.2010.574","article-title":"Genome-wide analysis of genetic loci associated with Alzheimer disease","volume":"303","author":"Seshadri","year":"2010","journal-title":"JAMA"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1452","DOI":"10.1038\/ng.2802","article-title":"Meta-analysis of 74,046 individuals identifies 11 new susceptibility loci for Alzheimer\u2019s disease","volume":"45","author":"Lambert","year":"2013","journal-title":"Nat. Genet."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"230","DOI":"10.1159\/000353395","article-title":"Effect of proinflammatory gene polymorphisms on the risk of Alzheimer\u2019s disease","volume":"13","author":"Flex","year":"2014","journal-title":"Neurodegener. Dis."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"436","DOI":"10.1038\/ng.801","article-title":"Common variants at MS4A4\/MS4A6E, CD2AP, CD33 and EPHA1 are associated with late-onset Alzheimer\u2019s disease","volume":"43","author":"Naj","year":"2011","journal-title":"Nat. Genet."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1088","DOI":"10.1038\/ng.440","article-title":"Genome-wide association study identifies variants at CLU and PICALM associated with Alzheimer\u2019s disease","volume":"41","author":"Harold","year":"2009","journal-title":"Nat. Genet."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1094","DOI":"10.1038\/ng.439","article-title":"Genome-wide association study identifies variants at CLU and CR1 associated with Alzheimer\u2019s disease","volume":"41","author":"Lambert","year":"2009","journal-title":"Nat. Genet."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"141","DOI":"10.3233\/JAD-2010-100123","article-title":"Polymorphic variation in cytochrome oxidase subunit genes","volume":"21","author":"Lu","year":"2010","journal-title":"J. Alzheimer\u2019s Dis."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1630","DOI":"10.1002\/humu.22167","article-title":"Exploratory data from complete genomes of familial alzheimer disease age-at-onset outliers","volume":"33","author":"Lalli","year":"2012","journal-title":"Hum. Mutat."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"11295","DOI":"10.1038\/ncomms11295","article-title":"Untangling the brain\u2019s neuroinflammatory and neurodegenerative transcriptional responses","volume":"7","author":"Srinivasan","year":"2016","journal-title":"Nat. Commun."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"34","DOI":"10.1186\/alzrt137","article-title":"Pooled-DNA sequencing identifies novel causative variants in PSEN1, GRN and MAPT in a clinical early-onset and familial Alzheimer\u2019s disease Ibero-American cohort","volume":"4","author":"Jin","year":"2012","journal-title":"Alzheimer\u2019s Res."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"733","DOI":"10.3233\/JAD-122407","article-title":"Association between interleukin 6 gene haplotype and Alzheimer\u2019s disease: A Brazilian case-control study","volume":"36","author":"Rasmussen","year":"2013","journal-title":"J Alzheimer\u2019s Dis."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"268","DOI":"10.1016\/j.cca.2010.10.015","article-title":"A single nucleotide polymorphism in LRP2 is associated with susceptibility to Alzheimer\u2019s disease in the Chinese population","volume":"412","author":"Wang","year":"2011","journal-title":"Clin. Chim. Acta"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"336","DOI":"10.1016\/0169-328X(94)90147-3","article-title":"Impairment in mitochondrial cytochrome oxidase gene expression in Alzheimer disease","volume":"24","author":"Chandrasekaran","year":"1994","journal-title":"Mol. Brain Res."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"207","DOI":"10.1159\/000333799","article-title":"Pin1 contribution to Alzheimer\u2019s disease: Transcriptional and epigenetic mechanisms in patients with late-onset Alzheimer\u2019s disease","volume":"10","author":"Arosio","year":"2012","journal-title":"Neurodegener. Dis."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1056\/NEJMoa1211851","article-title":"TREM2 variants in Alzheimer\u2019s disease","volume":"368","author":"Guerreiro","year":"2013","journal-title":"N. Engl. J. Med."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"314","DOI":"10.1159\/000051276","article-title":"Decreased Levels of Intrathecal Interleukin 1 Receptor Antagonist in Alzheimer\u2019s Disease","volume":"12","author":"Tarkowski","year":"2001","journal-title":"Dement. Geriatr. Cogn. Disord."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"565","DOI":"10.1016\/j.bbrc.2011.07.127","article-title":"CXCL8 protects human neurons from amyloid-beta-induced neurotoxicity: Relevance to Alzheimer\u2019s disease","volume":"412","author":"Ashutosh","year":"2011","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1089\/rej.2006.9.99","article-title":"Association between the HLA-A2 allele and Alzheimer disease","volume":"9","author":"Listi","year":"2006","journal-title":"Rejuvenation Res."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"754","DOI":"10.1016\/j.bbalip.2010.04.005","article-title":"Genetic evidence for the involvement of lipid metabolism in Alzheimer\u2019s disease","volume":"1801","author":"Jones","year":"2010","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"21","DOI":"10.3233\/JAD-161047","article-title":"Amyloid burden in obstructive sleep apnea","volume":"59","author":"Yun","year":"2017","journal-title":"J. Alzheimer\u2019s Dis."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"154","DOI":"10.1002\/ana.24672","article-title":"Obstructive sleep apnea decreases central nervous system-derived proteins in the cerebrospinal fluid","volume":"80","author":"Ju","year":"2016","journal-title":"Ann. Neurol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"1318","DOI":"10.1016\/j.neurobiolaging.2013.12.030","article-title":"The interaction between sleep-disordered breathing and apolipoprotein E genotype on cerebrospinal fluid biomarkers for Alzheimer\u2019s disease in cognitively normal elderly individuals","volume":"35","author":"Osorio","year":"2014","journal-title":"Neurobiol. Aging"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"zsz048","DOI":"10.1093\/sleep\/zsz048","article-title":"Obstructive sleep apnea and longitudinal Alzheimer\u2019s disease biomarker changes","volume":"42","author":"Bubu","year":"2019","journal-title":"Sleep"},{"key":"ref_42","first-page":"zsx011","article-title":"Obstructive sleep apnea is associated with early but possibly modifiable Alzheimer\u2019s disease biomarkers changes","volume":"40","author":"Liguori","year":"2017","journal-title":"Sleep"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"475","DOI":"10.5664\/jcsm.27938","article-title":"Does snoring intensity correlate with the severity of obstructive sleep apnea?","volume":"6","author":"Maimon","year":"2010","journal-title":"J. Clin. Sleep Med."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"189","DOI":"10.1016\/0022-3956(75)90026-6","article-title":"\u201cMini-mental state\u201d","volume":"12","author":"Folstein","year":"1975","journal-title":"J. Psychiatr. Res."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1038\/nrg2484","article-title":"RNA-Seq: A revolutionary tool for transcriptomics","volume":"10","author":"Wang","year":"2009","journal-title":"Nat. Rev. Genet."},{"key":"ref_46","doi-asserted-by":"crossref","unstructured":"Li, B., and Dewey, C.N. (2011). RSEM: Accurate transcript quantification from RNA-Seq data with or without a reference genome. BMC Bioinform., 12.","DOI":"10.1186\/1471-2105-12-323"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"986","DOI":"10.1101\/gr.7.10.986","article-title":"The significance of digital gene expression profiles","volume":"7","author":"Audic","year":"1997","journal-title":"Genome Res."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"1165","DOI":"10.1214\/aos\/1013699998","article-title":"The control of the false discovery rate in multiple testing under dependency","volume":"29","author":"Benjamini","year":"2001","journal-title":"Ann Stat."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"44","DOI":"10.1038\/nprot.2008.211","article-title":"Systematic and integrative analysis of large gene lists using DAVID bioinformatics resources","volume":"4","author":"Huang","year":"2009","journal-title":"Nat. Protoc."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"D480","DOI":"10.1093\/nar\/gkm882","article-title":"KEGG for linking genomes to life and the environment","volume":"36","author":"Kanehisa","year":"2008","journal-title":"Nucleic Acids Res."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1016\/j.gene.2016.10.022","article-title":"Integrated late onset Alzheimer\u2019s disease (LOAD) susceptibility genes: Cholesterol metabolism and trafficking perspectives","volume":"597","author":"Dong","year":"2017","journal-title":"Gene"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1016\/j.jneuroim.2012.03.012","article-title":"Association of interleukin 1beta polymorphisms and haplotypes with Alzheimer\u2019s disease","volume":"247","author":"Payao","year":"2012","journal-title":"J. Neuroimmunol."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"719","DOI":"10.1007\/s11325-015-1288-6","article-title":"Roles of interleukin (IL)-6 gene polymorphisms, serum IL-6 levels, and treatment in obstructive sleep apnea: A meta-analysis","volume":"20","author":"Zhong","year":"2016","journal-title":"Sleep Breath"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"425","DOI":"10.1007\/s11325-015-1252-5","article-title":"Increased MCP-1 gene expression in monocytes of severe OSA patients and under intermittent hypoxia","volume":"20","author":"Chuang","year":"2016","journal-title":"Sleep Breath"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"233","DOI":"10.1002\/gps.3816","article-title":"Increased systemic inflammatory interleukin-1ss and interleukin-6 during agitation as predictors of Alzheimer\u2019s disease","volume":"28","author":"Honma","year":"2013","journal-title":"Int. J. Geriatr. Psychiatry"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"1763","DOI":"10.1016\/j.neurobiolaging.2005.10.007","article-title":"Serum MCP-1 levels are increased in mild cognitive impairment and mild Alzheimer\u2019s disease","volume":"27","author":"Galimberti","year":"2006","journal-title":"Neurobiol. Aging"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"1902","DOI":"10.1212\/01.wnl.0000263217.36439.da","article-title":"Inflammatory markers and the risk of Alzheimer disease: The Framingham Study","volume":"68","author":"Tan","year":"2007","journal-title":"Neurology"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"1105","DOI":"10.3233\/JAD-140669","article-title":"Longitudinal Protein Changes in Blood Plasma Associated with the Rate of Cognitive Decline in Alzheimer\u2019s Disease","volume":"49","author":"Sattlecker","year":"2016","journal-title":"J. Alzheimer\u2019s Dis."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"1360","DOI":"10.1002\/jnr.23986","article-title":"Inflammasomes, hormesis, and antioxidants in neuroinflammation: Role of NRLP3 in Alzheimer disease","volume":"95","author":"Pennisi","year":"2017","journal-title":"J. Neurosci. Res."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"78","DOI":"10.3389\/fnagi.2016.00078","article-title":"The Association Between Obstructive Sleep Apnea and Alzheimer\u2019s Disease: A Meta-Analysis Perspective","volume":"8","author":"Emamian","year":"2016","journal-title":"Front. Aging Neurosci."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"258","DOI":"10.1111\/j.1532-5415.1991.tb01647.x","article-title":"Dementia in Institutionalized Elderly: Relation to Sleep Apnea","volume":"39","author":"Klauber","year":"1991","journal-title":"J. Am. Geriatr. Soc."}],"container-title":["Journal of Clinical Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2077-0383\/8\/9\/1361\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T13:15:53Z","timestamp":1760188553000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2077-0383\/8\/9\/1361"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,9,1]]},"references-count":61,"journal-issue":{"issue":"9","published-online":{"date-parts":[[2019,9]]}},"alternative-id":["jcm8091361"],"URL":"https:\/\/doi.org\/10.3390\/jcm8091361","relation":{},"ISSN":["2077-0383"],"issn-type":[{"value":"2077-0383","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,9,1]]}}}