{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T16:06:43Z","timestamp":1791475603573,"version":"4.3.4"},"reference-count":212,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2023,10,24]],"date-time":"2023-10-24T00:00:00Z","timestamp":1698105600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Ainsworth Medical Research Fund"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biomolecules"],"abstract":"<jats:p>Alzheimer\u2019s disease (AD) is a complex neurodegenerative disorder characterized by progressive cognitive decline and memory impairment. Many possible factors might contribute to the development of AD, including amyloid peptide and tau deposition, but more recent evidence suggests that neuroinflammation may also play an\u2014at least partial\u2014role in its pathogenesis. In recent years, emerging research has explored the possible involvement of external, invading pathogens in starting or accelerating the neuroinflammatory processes in AD. In this narrative review, we advance the hypothesis that neuroinflammation in AD might be partially caused by viral, bacterial, and fungal pathogens entering the brain through the nose and the olfactory system. The olfactory system represents a plausible route for pathogen entry, given its direct anatomical connection to the brain and its involvement in the early stages of AD. We discuss the potential mechanisms through which pathogens may exploit the olfactory pathway to initiate neuroinflammation, one of them being accidental exposure of the olfactory mucosa to hands contaminated with soil and feces when picking one\u2019s nose.<\/jats:p>","DOI":"10.3390\/biom13111568","type":"journal-article","created":{"date-parts":[[2023,10,24]],"date-time":"2023-10-24T06:28:25Z","timestamp":1698128905000},"page":"1568","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["Neuroinflammation in Alzheimer\u2019s Disease: A Potential Role of Nose-Picking in Pathogen Entry via the Olfactory System?"],"prefix":"10.3390","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8766-8158","authenticated-orcid":false,"given":"Xian","family":"Zhou","sequence":"first","affiliation":[{"name":"NICM Health Research Institute, Western Sydney University, Westmead, NSW 2145, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paayal","family":"Kumar","sequence":"additional","affiliation":[{"name":"Pharmacology Unit, School of Medicine, Western Sydney University, Campbelltown, NSW 2560, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9736-0197","authenticated-orcid":false,"given":"Deep J.","family":"Bhuyan","sequence":"additional","affiliation":[{"name":"NICM Health Research Institute, Western Sydney University, Westmead, NSW 2145, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4489-589X","authenticated-orcid":false,"given":"Slade O.","family":"Jensen","sequence":"additional","affiliation":[{"name":"Ingham Institute for Applied Medical Research, Liverpool, NSW 2170, Australia"},{"name":"Microbiology and Infectious Diseases Unit, School of Medicine, Western Sydney University, Liverpool, NSW 2170, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9266-0943","authenticated-orcid":false,"given":"Tara L.","family":"Roberts","sequence":"additional","affiliation":[{"name":"Ingham Institute for Applied Medical Research, Liverpool, NSW 2170, Australia"},{"name":"Oncology Unit, School of Medicine, Western Sydney University, Liverpool, NSW 2170, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gerald W.","family":"M\u00fcnch","sequence":"additional","affiliation":[{"name":"NICM Health Research Institute, Western Sydney University, Westmead, NSW 2145, Australia"},{"name":"Pharmacology Unit, School of Medicine, Western Sydney University, Campbelltown, NSW 2560, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,10,24]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"53","DOI":"10.5535\/arm.22027","article-title":"Dementia Epidemiology Fact Sheet 2022","volume":"46","author":"Shin","year":"2022","journal-title":"Ann. Rehabil. Med."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"207","DOI":"10.1007\/s00401-014-1371-2","article-title":"Tau aggregation and its interplay with amyloid-beta","volume":"129","author":"Nisbet","year":"2015","journal-title":"Acta Neuropathol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1291","DOI":"10.1111\/ejn.15599","article-title":"A closer look at the mycobiome in Alzheimer\u2019s disease: Fungal species, pathogenesis and transmission","volume":"55","author":"Phuna","year":"2022","journal-title":"Eur. J. Neurosci."},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Millington, C., Sonego, S., Karunaweera, N., Rangel, A., Aldrich-Wright, J.R., Campbell, I.L., Gyengesi, E., and M\u00fcnch, G. (2014). Chronic neuroinflammation in Alzheimer\u2019s disease: New perspectives on animal models and promising candidate drugs. BioMed Res. Int., 2014.","DOI":"10.1155\/2014\/309129"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1007\/s10571-014-0101-6","article-title":"Microglial Abeta receptors in Alzheimer\u2019s disease","volume":"35","author":"Yu","year":"2015","journal-title":"Cell Mol. Neurobiol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"813","DOI":"10.1046\/j.1460-9568.2003.02506.x","article-title":"beta-Amyloid peptide potentiates inflammatory responses induced by lipopolysaccharide, interferon -gamma and \u2018advanced glycation endproducts\u2019 in a murine microglia cell line","volume":"17","author":"Gartner","year":"2003","journal-title":"Eur. J. Neurosci."},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Vojtechova, I., Machacek, T., Kristofikova, Z., Stuchlik, A., and Petrasek, T. (2022). Infectious origin of Alzheimer\u2019s disease: Amyloid beta as a component of brain antimicrobial immunity. PLoS Pathog., 18.","DOI":"10.1371\/journal.ppat.1010929"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"340ra372","DOI":"10.1126\/scitranslmed.aaf1059","article-title":"Amyloid-beta peptide protects against microbial infection in mouse and worm models of Alzheimer\u2019s disease","volume":"8","author":"Kumar","year":"2016","journal-title":"Sci. Transl. Med."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"859","DOI":"10.3233\/JAD-160517","article-title":"Anti-Viral Properties of Amyloid-beta Peptides","volume":"54","author":"Bourgade","year":"2016","journal-title":"J. Alzheimers Dis."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"742065","DOI":"10.3389\/fnins.2021.742065","article-title":"Microglia in Neuroinflammation and Neurodegeneration: From Understanding to Therapy","volume":"15","author":"Muzio","year":"2021","journal-title":"Front. Neurosci."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"105212","DOI":"10.1016\/j.neuint.2021.105212","article-title":"Cellular and molecular influencers of neuroinflammation in Alzheimer\u2019s disease: Recent concepts & roles","volume":"151","author":"Ghosh","year":"2021","journal-title":"Neurochem. Int."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1002\/glia.440090305","article-title":"Early and rapid de novo synthesis of Alzheimer beta A4-amyloid precursor protein (APP) in activated microglia","volume":"9","author":"Banati","year":"1993","journal-title":"Glia"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1017\/S1461145711000149","article-title":"Increased NF-kappaB signalling up-regulates BACE1 expression and its therapeutic potential in Alzheimer\u2019s disease","volume":"15","author":"Chen","year":"2012","journal-title":"Int. J. Neuropsychopharmacol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"833","DOI":"10.1016\/j.neuron.2011.07.001","article-title":"Nitration of tyrosine 10 critically enhances amyloid beta aggregation and plaque formation","volume":"71","author":"Kummer","year":"2011","journal-title":"Neuron"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"307","DOI":"10.3109\/00207454.2013.833510","article-title":"Microglia, neuroinflammation, and beta-amyloid protein in Alzheimer\u2019s disease","volume":"124","author":"Cai","year":"2014","journal-title":"Int. J. Neurosci."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"165","DOI":"10.1186\/s12974-023-02853-3","article-title":"Tau and neuroinflammation in Alzheimer\u2019s disease: Interplay mechanisms and clinical translation","volume":"20","author":"Chen","year":"2023","journal-title":"J. Neuroinflamm."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"5628","DOI":"10.12998\/wjcc.v11.i24.5628","article-title":"Effect of pesticides on phosphorylation of tau protein, and its influence on Alzheimer\u2019s disease","volume":"11","author":"Ortiz","year":"2023","journal-title":"World J. Clin. Cases"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"395","DOI":"10.1038\/s41582-023-00822-1","article-title":"Functional roles of reactive astrocytes in neuroinflammation and neurodegeneration","volume":"19","author":"Patani","year":"2023","journal-title":"Nat. Rev. Neurol."},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Song, L., Wells, E.A., and Robinson, A.S. (2021). Critical Molecular and Cellular Contributors to Tau Pathology. Biomedicines, 9.","DOI":"10.3390\/biomedicines9020190"},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Thangaleela, S., Sivamaruthi, B.S., Kesika, P., Bharathi, M., and Chaiyasut, C. (2022). Nasal Microbiota, Olfactory Health, Neurological Disorders and Aging-A Review. Microorganisms, 10.","DOI":"10.3390\/microorganisms10071405"},{"key":"ref_21","first-page":"394","article-title":"Rhinotillexomania: A Manifestation of Psychiatric Illness","volume":"72","year":"2021","journal-title":"Acta Otorrinolaringol. Esp."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1007\/s004300050071","article-title":"Identification and localization of Chlamydia pneumoniae in the Alzheimer\u2019s brain","volume":"187","author":"Balin","year":"1998","journal-title":"Med. Microbiol. Immunol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"629","DOI":"10.1016\/j.neurobiolaging.2003.12.022","article-title":"Challenges and directions for the pathogen hypothesis of Alzheimer\u2019s disease","volume":"25","author":"Robinson","year":"2004","journal-title":"Neurobiol. Aging"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"157114","DOI":"10.1016\/j.scitotenv.2022.157114","article-title":"Increased occurrence of Treponema spp. and double-species infections in patients with Alzheimer\u2019s disease","volume":"844","author":"Nemergut","year":"2022","journal-title":"Sci. Total Environ."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1071","DOI":"10.1080\/00207454.2022.2045290","article-title":"A reappraisal on amyloid cascade hypothesis: The role of chronic infection in Alzheimer\u2019s disease","volume":"133","author":"Phuna","year":"2022","journal-title":"Int. J. Neurosci."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1024998","DOI":"10.3389\/fimmu.2022.1024998","article-title":"Parasite infections, neuroinflammation, and potential contributions of gut microbiota","volume":"13","author":"Alloo","year":"2022","journal-title":"Front. Immunol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1186\/s12934-021-01520-7","article-title":"Multi-pathogen infections and Alzheimer\u2019s disease","volume":"20","author":"Vigasova","year":"2021","journal-title":"Microb. Cell Fact."},{"key":"ref_28","first-page":"496","article-title":"The \u201cviruses of love\u201d and cancer","volume":"40","author":"Aurelian","year":"1974","journal-title":"Am. J. Med. Technol."},{"key":"ref_29","first-page":"308","article-title":"Seroprevalence of herpes simplex virus type 1 and type 2\u2014Data from a hospital-based study in Varna, northeastern Bulgaria, 2019\u20132021","volume":"46","author":"Tsankova","year":"2023","journal-title":"New Microbiol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"e33","DOI":"10.1017\/S0950268823000183","article-title":"Epidemiology of herpes simplex virus type 1 and genital herpes in Australia and New Zealand: Systematic review, meta-analyses and meta-regressions","volume":"151","author":"AlMukdad","year":"2023","journal-title":"Epidemiol. Infect."},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Looker, K.J., Magaret, A.S., May, M.T., Turner, K.M., Vickerman, P., Gottlieb, S.L., and Newman, L.M. (2015). Global and Regional Estimates of Prevalent and Incident Herpes Simplex Virus Type 1 Infections in 2012. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0140765"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"345","DOI":"10.1177\/0956462412472822","article-title":"Seroprevalence of HSV-1 and HSV-2 antibodies in Canadian women screened for enrolment in a herpes simplex virus vaccine trial","volume":"24","author":"Gorfinkel","year":"2013","journal-title":"Int. J. STD AIDS"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"171","DOI":"10.1016\/0039-6257(76)90095-3","article-title":"The biology of herpes simplex virus infection in humans","volume":"21","author":"Baringer","year":"1976","journal-title":"Surv. Ophthalmol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"766","DOI":"10.1093\/aje\/kwaa240","article-title":"Common Childhood Viruses and Pubertal Timing: The LEGACY Girls Study","volume":"190","author":"McDonald","year":"2021","journal-title":"Am. J. Epidemiol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"e002388","DOI":"10.1136\/bmjgh-2020-002388","article-title":"Herpes simplex virus type 1 in Europe: Systematic review, meta-analyses and meta-regressions","volume":"5","author":"Yousuf","year":"2020","journal-title":"BMJ Glob. Health"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"1656","DOI":"10.1016\/j.jocn.2013.12.023","article-title":"Primary herpes virus infection and ischemic stroke in childhood: A new association?","volume":"21","author":"Terlizzi","year":"2014","journal-title":"J. Clin. Neurosci."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"2963","DOI":"10.1073\/pnas.0806660106","article-title":"Early childhood stress is associated with elevated antibody levels to herpes simplex virus type 1","volume":"106","author":"Shirtcliff","year":"2009","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"303","DOI":"10.3109\/13550280009030756","article-title":"Asymptomatic herpes simplex type 1 virus infection of the mouse brain","volume":"6","author":"Boggian","year":"2000","journal-title":"J. Neurovirol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"27","DOI":"10.3109\/13550289809113479","article-title":"The comparative biology of latent herpes simplex virus type 1 and type 2 infections: Latency-associated transcript promoter activity and expression in vitro and in infected mice","volume":"4","author":"Wang","year":"1998","journal-title":"J. Neurovirol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"1999","DOI":"10.1007\/BF01718210","article-title":"Replication of herpes simplex virus type 1 and 2 in the medulla of the adrenal gland after vaginal infection of mice","volume":"141","author":"Podlech","year":"1996","journal-title":"Arch. Virol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"1989","DOI":"10.1089\/hum.1996.7.16-1989","article-title":"Long-term survival in a rodent model of disseminated brain tumors by combined intrathecal delivery of herpes vectors and ganciclovir treatment","volume":"7","author":"Kramm","year":"1996","journal-title":"Hum. Gene Ther."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1016\/S0959-437X(05)80345-4","article-title":"Herpesviruses: Expression of genes in postmitotic brain cells","volume":"3","author":"Geller","year":"1993","journal-title":"Curr. Opin. Genet. Dev."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"435","DOI":"10.1016\/0042-6822(89)90186-4","article-title":"Herpes simplex virus neurovirulence and productive infection of neural cells is associated with a function which maps between 0.82 and 0.832 map units on the HSV genome","volume":"172","author":"Thompson","year":"1989","journal-title":"Virology"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"790","DOI":"10.1038\/nrn2953","article-title":"Neuroimmunology: Keeping HSV-1 dormant","volume":"11","author":"David","year":"2010","journal-title":"Nat. Rev. Neurosci."},{"key":"ref_45","first-page":"378","article-title":"Herpes acquisition and transmission","volume":"4","author":"Burkhart","year":"2005","journal-title":"J. Drugs Dermatol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"849","DOI":"10.3233\/JAD-131706","article-title":"Inflammatory and neurodegeneration markers during asymptomatic HSV-1 reactivation","volume":"39","author":"Martin","year":"2014","journal-title":"J. Alzheimer\u2019s Dis. JAD"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1097\/00002093-198903030-00001","article-title":"In situ hybridization analysis for herpes simplex virus nucleic acids in Alzheimer disease","volume":"3","author":"Walker","year":"1989","journal-title":"Alzheimer Dis. Assoc. Disord."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"613","DOI":"10.1136\/jnnp.49.6.613","article-title":"Detection of HSV1 DNA by in situ hybridisation in human brain after immunosuppression","volume":"49","author":"Saldanha","year":"1986","journal-title":"J. Neurol. Neurosurg. Psychiatry"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"224","DOI":"10.1002\/jmv.1890330403","article-title":"Latent herpes simplex virus type 1 in normal and Alzheimer\u2019s disease brains","volume":"33","author":"Jamieson","year":"1991","journal-title":"J. Med. Virol."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"1027","DOI":"10.1016\/j.neuron.2019.12.031","article-title":"Human Herpesvirus 6 Detection in Alzheimer\u2019s Disease Cases and Controls across Multiple Cohorts","volume":"105","author":"Allnutt","year":"2020","journal-title":"Neuron"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"1761","DOI":"10.1074\/jbc.270.4.1761","article-title":"Effects of apoprotein E on intracellular metabolism of model triglyceride-rich particles are distinct from effects on cell particle uptake","volume":"270","author":"Schwiegelshohn","year":"1995","journal-title":"J. Biol. Chem."},{"key":"ref_52","first-page":"128","article-title":"Apolipoprotein E in the brain and its role in Alzheimer\u2019s disease","volume":"21","author":"Poirier","year":"1996","journal-title":"J. Psychiatry Neurosci. JPN"},{"key":"ref_53","first-page":"1485","article-title":"Human apolipoprotein E: The Alzheimer\u2019s disease connection","volume":"10","author":"Weisgraber","year":"1996","journal-title":"FASEB J. Off. Publ. Fed. Am. Soc. Exp. Biol."},{"key":"ref_54","first-page":"27","article-title":"Genes contributing to Alzheimer\u2019s disease","volume":"1","author":"Sandbrink","year":"1996","journal-title":"Mol. Psychiatry"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"457","DOI":"10.1016\/S0197-4580(99)00055-X","article-title":"Herpes simplex virus type 1 and Alzheimer\u2019s disease","volume":"20","author":"Dobson","year":"1999","journal-title":"Neurobiol. Aging"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"102200","DOI":"10.1016\/j.coph.2022.102200","article-title":"Role of HSV-1 in Alzheimer\u2019s disease pathogenesis: A challenge for novel preventive\/therapeutic strategies","volume":"63","author":"Protto","year":"2022","journal-title":"Curr. Opin. Pharmacol."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"103340","DOI":"10.1016\/j.drudis.2022.103340","article-title":"Recent insights into viral infections as a trigger and accelerator in alzheimer\u2019s disease","volume":"27","author":"Vandenbroucke","year":"2022","journal-title":"Drug Discov. Today"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"695738","DOI":"10.3389\/fncel.2021.695738","article-title":"The Hippocampal Vulnerability to Herpes Simplex Virus Type I Infection: Relevance to Alzheimer\u2019s Disease and Memory Impairment","volume":"15","author":"Yong","year":"2021","journal-title":"Front. Cell. Neurosci."},{"key":"ref_59","doi-asserted-by":"crossref","unstructured":"Itzhaki, R.F. (2021). Overwhelming Evidence for a Major Role for Herpes Simplex Virus Type 1 (HSV1) in Alzheimer\u2019s Disease (AD); Underwhelming Evidence against. Vaccines, 9.","DOI":"10.3390\/vaccines9060679"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"529","DOI":"10.1016\/j.omtn.2023.07.031","article-title":"Apolipoprotein E and viral infection: Risks and Mechanisms","volume":"33","author":"Chen","year":"2023","journal-title":"Mol. Ther. Nucleic Acids"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"261","DOI":"10.1038\/s41392-022-01118-4","article-title":"APOE interacts with ACE2 inhibiting SARS-CoV-2 cellular entry and inflammation in COVID-19 patients","volume":"7","author":"Zhang","year":"2022","journal-title":"Signal Transduct. Target. Ther."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"359","DOI":"10.1016\/j.csbj.2017.05.003","article-title":"Apolipoprotein E\u2014A Multifunctional Protein with Implications in Various Pathologies as a Result of Its Structural Features","volume":"15","author":"Tudorache","year":"2017","journal-title":"Comput. Struct. Biotechnol. J."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"3216","DOI":"10.1096\/fj.201700360","article-title":"Herpes simplex virus type 1 and Alzheimer\u2019s disease: Possible mechanisms and signposts","volume":"31","author":"Itzhaki","year":"2017","journal-title":"FASEB J."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"417","DOI":"10.1007\/s13311-018-0611-x","article-title":"Anti-herpetic Medications and Reduced Risk of Dementia in Patients with Herpes Simplex Virus Infections-a Nationwide, Population-Based Cohort Study in Taiwan","volume":"15","author":"Tzeng","year":"2018","journal-title":"Neurotherapeutics"},{"key":"ref_65","doi-asserted-by":"crossref","unstructured":"Romanescu, C., Schreiner, T.G., and Mukovozov, I. (2022). The Role of Human Herpesvirus 6 Infection in Alzheimer\u2019s Disease Pathogenicity-A Theoretical Mosaic. J. Clin. Med., 11.","DOI":"10.3390\/jcm11113061"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"2407","DOI":"10.1007\/s40520-022-02170-4","article-title":"Association between human herpesvirus 6 (HHV-6) and cognitive function in the elderly population in Shenzhen, China","volume":"34","author":"Huang","year":"2022","journal-title":"Aging Clin. Exp. Res."},{"key":"ref_67","doi-asserted-by":"crossref","unstructured":"Santpere, G., Telford, M., Andres-Benito, P., Navarro, A., and Ferrer, I. (2020). The Presence of Human Herpesvirus 6 in the Brain in Health and Disease. Biomolecules, 10.","DOI":"10.3390\/biom10111520"},{"key":"ref_68","doi-asserted-by":"crossref","unstructured":"Romeo, M.A., Gilardini Montani, M.S., Gaeta, A., D\u2019Orazi, G., Faggioni, A., and Cirone, M. (2020). HHV-6A infection dysregulates autophagy\/UPR interplay increasing beta amyloid production and tau phosphorylation in astrocytoma cells as well as in primary neurons, possible molecular mechanisms linking viral infection to Alzheimer\u2019s disease. Biochim. Biophys. Acta Mol. Basis Dis., 1866.","DOI":"10.1016\/j.bbadis.2019.165647"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"1189","DOI":"10.3233\/JAD-220287","article-title":"Potential Involvement of Varicella Zoster Virus in Alzheimer\u2019s Disease via Reactivation of Quiescent Herpes Simplex Virus Type 1","volume":"88","author":"Cairns","year":"2022","journal-title":"J. Alzheimers Dis."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"363","DOI":"10.3233\/JAD-180266","article-title":"Herpes Viruses and Senile Dementia: First Population Evidence for a Causal Link","volume":"64","author":"Itzhaki","year":"2018","journal-title":"J. Alzheimers Dis."},{"key":"ref_71","doi-asserted-by":"crossref","unstructured":"Preda, M., Manolescu, L.S.C., and Chivu, R.D. (2023). Advances in Alpha Herpes Viruses Vaccines for Human. Vaccines, 11.","DOI":"10.3390\/vaccines11061094"},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"56","DOI":"10.1016\/j.trsl.2021.12.006","article-title":"An mRNA vaccine to prevent genital herpes","volume":"242","author":"Awasthi","year":"2022","journal-title":"Transl. Res."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"469","DOI":"10.21775\/cimb.041.469","article-title":"Alphaherpesvirus Vaccines","volume":"41","author":"Aschner","year":"2021","journal-title":"Curr. Issues Mol. Biol."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1007\/978-1-4939-9814-2_2","article-title":"Vaccines for Herpes Simplex: Recent Progress Driven by Viral and Adjuvant Immunology","volume":"2060","author":"Sandgren","year":"2020","journal-title":"Methods Mol. Biol."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"e12293","DOI":"10.1002\/trc2.12293","article-title":"Reduced dementia incidence after varicella zoster vaccination in Wales 2013\u20132020","volume":"8","author":"Schnier","year":"2022","journal-title":"Alzheimers Dement"},{"key":"ref_76","first-page":"395","article-title":"Infection control of herpes simplex virus infections in obstetrics and gynecology","volume":"31","author":"Gibbs","year":"1986","journal-title":"J. Reprod. Med."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1111\/j.1875-595X.2004.tb00263.x","article-title":"Herpes simplex virus: An occupational hazard in dentistry","volume":"54","author":"Lewis","year":"2004","journal-title":"Int. Dent. J."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"270","DOI":"10.1038\/s41586-020-2012-7","article-title":"A pneumonia outbreak associated with a new coronavirus of probable bat origin","volume":"579","author":"Zhou","year":"2020","journal-title":"Nature"},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"1018","DOI":"10.1001\/jamaneurol.2020.2065","article-title":"Neuropathogenesis and Neurologic Manifestations of the Coronaviruses in the Age of Coronavirus Disease 2019: A Review","volume":"77","author":"Zubair","year":"2020","journal-title":"JAMA Neurol."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"e89","DOI":"10.1093\/ibd\/izaa131","article-title":"Temporal Correlation Between Neurological and Gastrointestinal Symptoms of SARS-CoV-2","volume":"26","author":"Bostanciklioglu","year":"2020","journal-title":"Inflamm. Bowel Dis."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"159","DOI":"10.1016\/B978-0-323-98818-6.00014-5","article-title":"COVID-19 (novel SARS-CoV-2) neurological illness","volume":"195","author":"Younger","year":"2023","journal-title":"Handb. Clin. Neurol."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"1505","DOI":"10.1111\/ene.15721","article-title":"Functional neurological disorder in people with long COVID: A systematic review","volume":"30","author":"Teodoro","year":"2023","journal-title":"Eur. J. Neurol."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"311","DOI":"10.2147\/NDT.S387501","article-title":"Neurological Manifestations of Long COVID: A Single-Center One-Year Experience","volume":"19","author":"Taruffi","year":"2023","journal-title":"Neuropsychiatr. Dis. Treat."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"155","DOI":"10.1016\/j.jiph.2022.12.005","article-title":"Neurological Manifestations of hospitalized patients with mild to moderate infection with SARS-CoV-2 Omicron variant in Shanghai, China","volume":"16","author":"Shen","year":"2023","journal-title":"J. Infect. Public. Health"},{"key":"ref_85","first-page":"69","article-title":"Neurological Involvements in COVID-19: A hospital-based study","volume":"17","author":"Montazerlotfelahi","year":"2023","journal-title":"Iran. J. Child. Neurol."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"416","DOI":"10.1016\/S2215-0366(21)00084-5","article-title":"6-month neurological and psychiatric outcomes in 236 379 survivors of COVID-19: A retrospective cohort study using electronic health records","volume":"8","author":"Taquet","year":"2021","journal-title":"Lancet Psychiatry"},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"171","DOI":"10.1017\/cjn.2021.70","article-title":"Effects of the COVID-19 Pandemic on Parkinson\u2019s Disease: A Single-Centered Qualitative Study","volume":"49","author":"Anghelescu","year":"2022","journal-title":"Can. J. Neurol. Sci."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"1953","DOI":"10.1002\/acn3.51688","article-title":"COVID-19 and the risk of Alzheimer\u2019s disease, amyotrophic lateral sclerosis, and multiple sclerosis","volume":"9","author":"Zhang","year":"2022","journal-title":"Ann. Clin. Transl. Neurol."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"283","DOI":"10.1038\/s41398-022-02052-3","article-title":"COVID-19 and risk of neurodegenerative disorders: A Mendelian randomization study","volume":"12","author":"Li","year":"2022","journal-title":"Transl. Psychiatry"},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"119","DOI":"10.3233\/ADR-220090","article-title":"The Effects of SARS-CoV-2 Infection on the Cognitive Functioning of Patients with Pre-Existing Dementia","volume":"7","author":"Dubey","year":"2023","journal-title":"J. Alzheimers Dis. Rep."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"152057","DOI":"10.1016\/j.anndiagpath.2022.152057","article-title":"The amplification of CNS damage in Alzheimer\u2019s disease due to SARS-CoV2 infection","volume":"61","author":"Nuovo","year":"2022","journal-title":"Ann. Diagn. Pathol."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"973","DOI":"10.30773\/pi.2022.0179","article-title":"The Impact of the COVID-19 Pandemic and Social Distancing on Cognition of Alzheimer\u2019s Disease Patients","volume":"19","author":"Joo","year":"2022","journal-title":"Psychiatry Investig."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1186\/s40035-021-00237-2","article-title":"COVID-19 and Alzheimer\u2019s disease: How one crisis worsens the other","volume":"10","author":"Xia","year":"2021","journal-title":"Transl. Neurodegener."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"883","DOI":"10.3233\/JAD-210335","article-title":"Dementia and COVID-19, a Bidirectional Liaison: Risk Factors, Biomarkers, and Optimal Health Care","volume":"82","author":"Toniolo","year":"2021","journal-title":"J. Alzheimers Dis."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"1086","DOI":"10.1016\/j.neuron.2022.12.029","article-title":"Virus exposure and neurodegenerative disease risk across national biobanks","volume":"111","author":"Levine","year":"2023","journal-title":"Neuron"},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"75","DOI":"10.1016\/j.neurobiolaging.2022.12.004","article-title":"Signatures for viral infection and inflammation in the proximal olfactory system in familial Alzheimer\u2019s disease","volume":"123","author":"Bubak","year":"2023","journal-title":"Neurobiol. Aging"},{"key":"ref_97","unstructured":"Gautam, J., and Krawiec, C. (2023). StatPearls, Treasure Island (FL) Ineligible Companies."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"1527","DOI":"10.7754\/Clin.Lab.2021.210908","article-title":"Systematic Infection of Chlamydia Pneumoniae","volume":"68","author":"Ma","year":"2022","journal-title":"Clin. Lab."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"355","DOI":"10.1111\/j.1574-695X.2006.00154.x","article-title":"Chlamydophila (Chlamydia) pneumoniae in the Alzheimer\u2019s brain","volume":"48","author":"Gerard","year":"2006","journal-title":"FEMS Immunol. Med. Microbiol."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"2591","DOI":"10.1128\/JCM.38.7.2591-2594.2000","article-title":"Failure to detect Chlamydia pneumoniae in the late-onset Alzheimer\u2019s brain","volume":"38","author":"Ring","year":"2000","journal-title":"J. Clin. Microbiol."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"1888","DOI":"10.1212\/WNL.53.8.1888-a","article-title":"Failure to detect Chlamydia pneumoniae in brain tissues of Alzheimer\u2019s disease","volume":"53","author":"Nochlin","year":"1999","journal-title":"Neurology"},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"957","DOI":"10.3233\/JAD-140621","article-title":"Bacterial infection and Alzheimer\u2019s disease: A meta-analysis","volume":"43","author":"Maheshwari","year":"2015","journal-title":"J. Alzheimers Dis."},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"2759","DOI":"10.1038\/s41598-022-06749-9","article-title":"Chlamydia pneumoniae can infect the central nervous system via the olfactory and trigeminal nerves and contributes to Alzheimer\u2019s disease risk","volume":"12","author":"Chacko","year":"2022","journal-title":"Sci. Rep."},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"419","DOI":"10.1016\/S0197-4580(03)00127-1","article-title":"Chlamydia pneumoniae induces Alzheimer-like amyloid plaques in brains of BALB\/c mice","volume":"25","author":"Little","year":"2004","journal-title":"Neurobiol. Aging"},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"217","DOI":"10.1186\/s12974-014-0217-0","article-title":"Chlamydia pneumoniae infection of monocytes in vitro stimulates innate and adaptive immune responses relevant to those in Alzheimer\u2019s disease","volume":"11","author":"Lim","year":"2014","journal-title":"J. Neuroinflamm."},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"1433","DOI":"10.1161\/ATVBAHA.106.138743","article-title":"Endotoxemia, immune response to periodontal pathogens, and systemic inflammation associate with incident cardiovascular disease events","volume":"27","author":"Pussinen","year":"2007","journal-title":"Arterioscler. Thromb. Vasc. Biol."},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"63","DOI":"10.1111\/j.1574-6968.1995.tb07915.x","article-title":"Binding of hemoglobin by Porphyromonas gingivalis","volume":"134","author":"Amano","year":"1995","journal-title":"FEMS Microbiol. Lett."},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"1932","DOI":"10.1128\/iai.59.6.1932-1940.1991","article-title":"Hemolytic activity in the periodontopathogen Porphyromonas gingivalis: Kinetics of enzyme release and localization","volume":"59","author":"Chu","year":"1991","journal-title":"Infect. Immun."},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"eaau3333","DOI":"10.1126\/sciadv.aau3333","article-title":"Porphyromonas gingivalis in Alzheimer\u2019s disease brains: Evidence for disease causation and treatment with small-molecule inhibitors","volume":"5","author":"Dominy","year":"2019","journal-title":"Sci. Adv."},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"479","DOI":"10.3233\/JAD-190298","article-title":"Porphyromonas gingivalis Infection Induces Amyloid-beta Accumulation in Monocytes\/Macrophages","volume":"72","author":"Nie","year":"2019","journal-title":"J. Alzheimers Dis."},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"120","DOI":"10.1016\/j.archoralbio.2019.01.008","article-title":"Porphyromonas gingivalis lipopolysaccharide-induced periodontitis and serum amyloid-beta peptides","volume":"99","author":"Leira","year":"2019","journal-title":"Arch. Oral. Biol."},{"key":"ref_112","doi-asserted-by":"crossref","unstructured":"Raineri, E.J.M., Altulea, D., and van Dijl, J.M. (2022). Staphylococcal trafficking and infection-from \u2018nose to gut\u2019 and back. FEMS Microbiol. Rev., 46.","DOI":"10.1093\/femsre\/fuab041"},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"7990","DOI":"10.1038\/s41598-023-35111-w","article-title":"The impact of methicillin resistance on clinical outcome among patients with Staphylococcus aureus osteomyelitis: A retrospective cohort study of 482 cases","volume":"13","author":"Wu","year":"2023","journal-title":"Sci. Rep."},{"key":"ref_114","doi-asserted-by":"crossref","unstructured":"Siciliano, V., Passerotto, R.A., Chiuchiarelli, M., Leanza, G.M., and Ojetti, V. (2023). Difficult-to-Treat Pathogens: A Review on the Management of Multidrug-Resistant Staphylococcus epidermidis. Life, 13.","DOI":"10.3390\/life13051126"},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"189","DOI":"10.1016\/j.ijid.2021.12.322","article-title":"Diagnosis, management, and outcomes of brain abscess due to gram-negative versus gram-positive bacteria","volume":"115","author":"Wilson","year":"2022","journal-title":"Int. J. Infect. Dis."},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"1349","DOI":"10.1007\/s10571-018-0609-2","article-title":"Mechanisms of Blood Brain Barrier Disruption by Different Types of Bacteria, and Bacterial-Host Interactions Facilitate the Bacterial Pathogen Invading the Brain","volume":"38","author":"Desa","year":"2018","journal-title":"Cell Mol. Neurobiol."},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"266","DOI":"10.3109\/08830185.2013.823422","article-title":"Role of pathogens in multiple sclerosis","volume":"33","author":"Libbey","year":"2014","journal-title":"Int. Rev. Immunol."},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"480739","DOI":"10.1155\/2013\/480739","article-title":"Cytokines and chemokines at the crossroads of neuroinflammation, neurodegeneration, and neuropathic pain","volume":"2013","author":"Ramesh","year":"2013","journal-title":"Mediat. Inflamm."},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"32228","DOI":"10.1038\/srep32228","article-title":"Amyloidogenic amyloid-beta-peptide variants induce microbial agglutination and exert antimicrobial activity","volume":"6","author":"Spitzer","year":"2016","journal-title":"Sci. Rep."},{"key":"ref_120","doi-asserted-by":"crossref","unstructured":"Lim, J.Y., Lee, J.E., Kim, H.K., Park, Y.J., Jeon, J.H., Park, S.A., Lee, N., Lee, I.H., Kim, D.H., and Yang, S.H. (2022). Human Palatine Tonsils Are Linked to Alzheimer\u2019s Disease through Function of Reservoir of Amyloid Beta Protein Associated with Bacterial Infection. Cells, 11.","DOI":"10.3390\/cells11152285"},{"key":"ref_121","doi-asserted-by":"crossref","first-page":"112785","DOI":"10.1016\/j.celrep.2023.112785","article-title":"Multi-transcriptomics reveals brain cellular responses to peripheral infection in Alzheimer\u2019s disease model mice","volume":"42","author":"Lu","year":"2023","journal-title":"Cell Rep."},{"key":"ref_122","doi-asserted-by":"crossref","first-page":"4584","DOI":"10.3390\/cimb44100314","article-title":"Implications of Microorganisms in Alzheimer\u2019s Disease","volume":"44","author":"Yadav","year":"2022","journal-title":"Curr. Issues Mol. Biol."},{"key":"ref_123","doi-asserted-by":"crossref","first-page":"139","DOI":"10.3233\/ADR-180073","article-title":"Innate Immune and Fungal Model of Alzheimer\u2019s Disease","volume":"2","author":"Parady","year":"2018","journal-title":"J. Alzheimers Dis. Rep."},{"key":"ref_124","doi-asserted-by":"crossref","first-page":"15015","DOI":"10.1038\/srep15015","article-title":"Different Brain Regions are Infected with Fungi in Alzheimer\u2019s Disease","volume":"5","author":"Pisa","year":"2015","journal-title":"Sci. Rep."},{"key":"ref_125","doi-asserted-by":"crossref","unstructured":"Soscia, S.J., Kirby, J.E., Washicosky, K.J., Tucker, S.M., Ingelsson, M., Hyman, B., Burton, M.A., Goldstein, L.E., Duong, S., and Tanzi, R.E. (2010). The Alzheimer\u2019s disease-associated amyloid beta-protein is an antimicrobial peptide. PLoS ONE, 5.","DOI":"10.1371\/journal.pone.0009505"},{"key":"ref_126","doi-asserted-by":"crossref","first-page":"55","DOI":"10.3233\/JAD-170058","article-title":"Identification of Fungal Species in Brain Tissue from Alzheimer\u2019s Disease by Next-Generation Sequencing","volume":"58","author":"Alonso","year":"2017","journal-title":"J. Alzheimers Dis."},{"key":"ref_127","doi-asserted-by":"crossref","first-page":"362","DOI":"10.3389\/fgene.2018.00362","article-title":"Role of Microbes in the Development of Alzheimer\u2019s Disease: State of the Art\u2014An International Symposium Presented at the 2017 IAGG Congress in San Francisco","volume":"9","author":"Fulop","year":"2018","journal-title":"Front. Genet."},{"key":"ref_128","doi-asserted-by":"crossref","first-page":"1517","DOI":"10.1111\/j.1532-5415.2008.01826.x","article-title":"Olfaction and the 5-year incidence of cognitive impairment in an epidemiological study of older adults","volume":"56","author":"Schubert","year":"2008","journal-title":"J. Am. Geriatr. Soc."},{"key":"ref_129","doi-asserted-by":"crossref","first-page":"e1341","DOI":"10.1212\/WNL.0000000000207659","article-title":"Association of APOE epsilon4 Status With Long-term Declines in Odor Sensitivity, Odor Identification, and Cognition in Older US Adults","volume":"101","author":"GoodSmith","year":"2023","journal-title":"Neurology"},{"key":"ref_130","doi-asserted-by":"crossref","first-page":"857","DOI":"10.1016\/j.neubiorev.2021.11.009","article-title":"A potential biomarker of preclinical Alzheimer\u2019s disease: The olfactory dysfunction and its pathogenesis-based neural circuitry impairments","volume":"132","author":"Yan","year":"2022","journal-title":"Neurosci. Biobehav. Rev."},{"key":"ref_131","first-page":"265","article-title":"Olfactory tau pathology in Alzheimer disease and mild cognitive impairment","volume":"25","author":"Attems","year":"2006","journal-title":"Clin. Neuropathol."},{"key":"ref_132","doi-asserted-by":"crossref","unstructured":"Jellinger, K.A., and Attems, J. (2005). Alzheimer pathology in the olfactory bulb. Neuropathol. Appl. Neurobiol., 31.","DOI":"10.1111\/j.1365-2990.2004.00619.x"},{"key":"ref_133","doi-asserted-by":"crossref","first-page":"149","DOI":"10.3233\/JAD-2005-7208","article-title":"Olfactory involvement in aging and Alzheimer\u2019s disease: An autopsy study","volume":"7","author":"Attems","year":"2005","journal-title":"J. Alzheimers Dis."},{"key":"ref_134","doi-asserted-by":"crossref","first-page":"503","DOI":"10.1046\/j.1365-2990.2003.00453.x","article-title":"Tau pathology in the olfactory bulb correlates with Braak stage, Lewy body pathology and apolipoprotein epsilon4","volume":"29","author":"Tsuboi","year":"2003","journal-title":"Neuropathol. Appl. Neurobiol."},{"key":"ref_135","doi-asserted-by":"crossref","first-page":"481","DOI":"10.1046\/j.1365-2990.1999.00208.x","article-title":"beta-amyloid deposition and neurofibrillary tangle formation in the olfactory bulb in ageing and Alzheimer\u2019s disease","volume":"25","author":"Kovacs","year":"1999","journal-title":"Neuropathol. Appl. Neurobiol."},{"key":"ref_136","doi-asserted-by":"crossref","first-page":"205","DOI":"10.1177\/1533317513517049","article-title":"Possible link between Toxoplasma gondii and the anosmia associated with neurodegenerative diseases","volume":"29","author":"Prandota","year":"2014","journal-title":"Am. J. Alzheimers Dis. Other Demen."},{"key":"ref_137","doi-asserted-by":"crossref","first-page":"353","DOI":"10.1016\/0197-4580(93)90121-Q","article-title":"Axonal loss from the olfactory tracts in Alzheimer\u2019s disease","volume":"14","author":"Davies","year":"1993","journal-title":"Neurobiol. Aging"},{"key":"ref_138","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/0047-6374(88)90058-9","article-title":"Alzheimer\u2019s disease: An olfactory connection?","volume":"42","author":"Mann","year":"1988","journal-title":"Mech. Ageing Dev."},{"key":"ref_139","doi-asserted-by":"crossref","first-page":"4269","DOI":"10.1038\/s41467-018-06668-2","article-title":"The olfactory epithelium as a port of entry in neonatal neurolisteriosis","volume":"9","author":"Pagelow","year":"2018","journal-title":"Nat. Commun."},{"key":"ref_140","doi-asserted-by":"crossref","first-page":"277","DOI":"10.1002\/path.4461","article-title":"The olfactory nerve: A shortcut for influenza and other viral diseases into the central nervous system","volume":"235","author":"Verdijk","year":"2015","journal-title":"J. Pathol."},{"key":"ref_141","first-page":"1213","article-title":"Blood brain barrier and infection","volume":"6","author":"Chaudhuri","year":"2000","journal-title":"Med. Sci. Monit."},{"key":"ref_142","doi-asserted-by":"crossref","first-page":"261","DOI":"10.1007\/s004010050893","article-title":"Ultrastructural and permeability features of microvessels in the olfactory bulbs of SAM mice","volume":"96","author":"Ueno","year":"1998","journal-title":"Acta Neuropathol."},{"key":"ref_143","doi-asserted-by":"crossref","first-page":"619","DOI":"10.2174\/1381612828666211222163025","article-title":"Drug Delivery Systems and Strategies to Overcome the Barriers of Brain","volume":"28","author":"Garg","year":"2022","journal-title":"Curr. Pharm. Des."},{"key":"ref_144","first-page":"2088","article-title":"Nose to brain transport pathways an overview: Potential of nanostructured lipid carriers in nose to brain targeting","volume":"46","author":"Selvaraj","year":"2018","journal-title":"Artif. Cells Nanomed. Biotechnol."},{"key":"ref_145","doi-asserted-by":"crossref","first-page":"130","DOI":"10.1016\/j.neuro.2018.09.008","article-title":"The time course of blood brain barrier leakage and its implications on the progression of methamphetamine-induced seizures","volume":"69","author":"Bowyer","year":"2018","journal-title":"Neurotoxicology"},{"key":"ref_146","doi-asserted-by":"crossref","first-page":"337","DOI":"10.1016\/j.ejpb.2018.05.009","article-title":"Recent advances in carrier mediated nose-to-brain delivery of pharmaceutics","volume":"128","author":"Bourganis","year":"2018","journal-title":"Eur. J. Pharm. Biopharm."},{"key":"ref_147","doi-asserted-by":"crossref","first-page":"371","DOI":"10.1038\/jcbfm.2014.215","article-title":"Rapid transport within cerebral perivascular spaces underlies widespread tracer distribution in the brain after intranasal administration","volume":"35","author":"Lochhead","year":"2015","journal-title":"J. Cereb. Blood Flow. Metab."},{"key":"ref_148","doi-asserted-by":"crossref","first-page":"5471","DOI":"10.1210\/en.2004-0984","article-title":"17beta-estradiol differentially regulates blood-brain barrier permeability in young and aging female rats","volume":"145","author":"Bake","year":"2004","journal-title":"Endocrinology"},{"key":"ref_149","doi-asserted-by":"crossref","first-page":"8146","DOI":"10.1073\/pnas.97.14.8146","article-title":"Retrograde axonal transport of herpes simplex virus: Evidence for a single mechanism and a role for tegument","volume":"97","author":"Bearer","year":"2000","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_150","doi-asserted-by":"crossref","first-page":"5405","DOI":"10.1128\/jvi.70.8.5405-5413.1996","article-title":"Anterograde, transneuronal transport of herpes simplex virus type 1 strain H129 in the murine visual system","volume":"70","author":"Sun","year":"1996","journal-title":"J. Virol."},{"key":"ref_151","doi-asserted-by":"crossref","first-page":"447","DOI":"10.1111\/ene.12328","article-title":"Outcome of fulminant bacterial meningitis in adult patients","volume":"21","author":"Muralidharan","year":"2014","journal-title":"Eur. J. Neurol."},{"key":"ref_152","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1016\/j.micpath.2013.02.003","article-title":"Neisseria meningitidis serogroup B vaccine development","volume":"57","author":"Caesar","year":"2013","journal-title":"Microb. Pathog."},{"key":"ref_153","doi-asserted-by":"crossref","first-page":"287","DOI":"10.1007\/s11894-002-0078-z","article-title":"Update on Listeria monocytogenes infection","volume":"4","author":"Crum","year":"2002","journal-title":"Curr. Gastroenterol. Rep."},{"key":"ref_154","first-page":"463","article-title":"Bacterial meningitis in older children","volume":"144","author":"Bonadio","year":"1990","journal-title":"Am. J. Dis. Child."},{"key":"ref_155","doi-asserted-by":"crossref","first-page":"484","DOI":"10.1288\/00005537-197803000-00012","article-title":"Primary amoebic meningoencephalitis","volume":"88","author":"Lockey","year":"1978","journal-title":"Laryngoscope"},{"key":"ref_156","doi-asserted-by":"crossref","first-page":"42","DOI":"10.1186\/s13024-020-00378-4","article-title":"Microbial involvement in Alzheimer disease development and progression","volume":"15","author":"Bulgart","year":"2020","journal-title":"Mol. Neurodegener."},{"key":"ref_157","doi-asserted-by":"crossref","unstructured":"Mattos-Graner, R.O., Klein, M.I., and Alves, L.A. (2023). The complement system as a key modulator of the oral microbiome in health and disease. Crit. Rev. Microbiol., 1\u201330.","DOI":"10.1080\/1040841X.2022.2163614"},{"key":"ref_158","doi-asserted-by":"crossref","first-page":"730","DOI":"10.1080\/1040841X.2021.2025042","article-title":"Temporal development of the infant oral microbiome","volume":"48","author":"Blum","year":"2022","journal-title":"Crit. Rev. Microbiol."},{"key":"ref_159","doi-asserted-by":"crossref","unstructured":"Morrison, A.G., Sarkar, S., Umar, S., Lee, S.T.M., and Thomas, S.M. (2023). The Contribution of the Human Oral Microbiome to Oral Disease: A Review. Microorganisms, 11.","DOI":"10.3390\/microorganisms11020318"},{"key":"ref_160","doi-asserted-by":"crossref","first-page":"8","DOI":"10.3389\/fpsyt.2022.810008","article-title":"The Oral-Microbiome-Brain Axis and Neuropsychiatric Disorders: An Anthropological Perspective","volume":"13","author":"Bowland","year":"2022","journal-title":"Front. Psychiatry"},{"key":"ref_161","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1111\/prd.12429","article-title":"Periodontal microorganisms and Alzheimer disease\u2014A causative relationship?","volume":"89","author":"Jungbauer","year":"2022","journal-title":"Periodontol. 2000"},{"key":"ref_162","doi-asserted-by":"crossref","first-page":"1341","DOI":"10.1111\/odi.14110","article-title":"Profiling the oral microbiomes in patients with Alzheimer\u2019s disease","volume":"29","author":"Guo","year":"2023","journal-title":"Oral. Dis."},{"key":"ref_163","doi-asserted-by":"crossref","unstructured":"Noble, J.M., Scarmeas, N., Celenti, R.S., Elkind, M.S., Wright, C.B., Schupf, N., and Papapanou, P.N. (2014). Serum IgG antibody levels to periodontal microbiota are associated with incident Alzheimer disease. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0114959"},{"key":"ref_164","doi-asserted-by":"crossref","first-page":"196","DOI":"10.1016\/j.jalz.2011.04.006","article-title":"Serum antibodies to periodontal pathogens are a risk factor for Alzheimer\u2019s disease","volume":"8","author":"Steffen","year":"2012","journal-title":"Alzheimer\u2019s Dement. J. Alzheimer\u2019s Assoc."},{"key":"ref_165","doi-asserted-by":"crossref","first-page":"109","DOI":"10.12688\/f1000research.129036.2","article-title":"Studying ancient human oral microbiomes could yield insights into the evolutionary history of noncommunicable diseases","volume":"12","author":"Gancz","year":"2023","journal-title":"F1000Res"},{"key":"ref_166","doi-asserted-by":"crossref","first-page":"633","DOI":"10.3233\/JAD-190587","article-title":"Analysis of Salivary Microbiome in Patients with Alzheimer\u2019s Disease","volume":"72","author":"Liu","year":"2019","journal-title":"J. Alzheimers Dis."},{"key":"ref_167","doi-asserted-by":"crossref","unstructured":"Wu, Y.F., Lee, W.F., Salamanca, E., Yao, W.L., Su, J.N., Wang, S.Y., Hu, C.J., and Chang, W.J. (2021). Oral Microbiota Changes in Elderly Patients, an Indicator of Alzheimer\u2019s Disease. Int. J. Environ. Res. Public. Health, 18.","DOI":"10.3390\/ijerph18084211"},{"key":"ref_168","doi-asserted-by":"crossref","first-page":"1762","DOI":"10.1016\/j.jds.2022.07.001","article-title":"Association of periodontitis and oral microbiomes with Alzheimer\u2019s disease: A narrative systematic review","volume":"17","author":"Mao","year":"2022","journal-title":"J. Dent. Sci."},{"key":"ref_169","doi-asserted-by":"crossref","first-page":"2324","DOI":"10.1212\/WNL.0000000000003391","article-title":"Gram-negative bacterial molecules associate with Alzheimer disease pathology","volume":"87","author":"Zhan","year":"2016","journal-title":"Neurology"},{"key":"ref_170","doi-asserted-by":"crossref","first-page":"106189","DOI":"10.1016\/j.phrs.2022.106189","article-title":"Dual role of the nasal microbiota in neurological diseases\u2014An unignorable risk factor or a potential therapy carrier","volume":"179","author":"Xie","year":"2022","journal-title":"Pharmacol. Res."},{"key":"ref_171","doi-asserted-by":"crossref","unstructured":"Harrass, S., Yi, C., and Chen, H. (2021). Chronic Rhinosinusitis and Alzheimer\u2019s Disease\u2014A Possible Role for the Nasal Microbiome in Causing Neurodegeneration in the Elderly. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms222011207"},{"key":"ref_172","doi-asserted-by":"crossref","first-page":"644","DOI":"10.1016\/j.neurol.2019.09.004","article-title":"Bacterial transportable toxins of the nasopharyngeal microbiota in multiple sclerosis. Nose-to-brain direct","volume":"175","author":"Gay","year":"2019","journal-title":"Rev. Neurol."},{"key":"ref_173","doi-asserted-by":"crossref","first-page":"302","DOI":"10.3389\/fnagi.2018.00302","article-title":"Chlamydia pneumoniae: An Etiologic Agent for Late-Onset Dementia","volume":"10","author":"Balin","year":"2018","journal-title":"Front. Aging Neurosci."},{"key":"ref_174","doi-asserted-by":"crossref","first-page":"158","DOI":"10.1111\/j.1600-065X.2012.01146.x","article-title":"PAMPs and DAMPs: Signal 0s that spur autophagy and immunity","volume":"249","author":"Tang","year":"2012","journal-title":"Immunol. Rev."},{"key":"ref_175","doi-asserted-by":"crossref","first-page":"126","DOI":"10.2174\/1570159X19666210826130210","article-title":"Neuroinflammatory Signaling in the Pathogenesis of Alzheimer\u2019s Disease","volume":"20","author":"Uddin","year":"2022","journal-title":"Curr. Neuropharmacol."},{"key":"ref_176","doi-asserted-by":"crossref","first-page":"2285","DOI":"10.1161\/CIRCULATIONAHA.112.000434","article-title":"Innate signaling promotes formation of regulatory nitric oxide-producing dendritic cells limiting T-cell expansion in experimental autoimmune myocarditis","volume":"127","author":"Kania","year":"2013","journal-title":"Circulation"},{"key":"ref_177","doi-asserted-by":"crossref","first-page":"443","DOI":"10.1111\/j.1574-695X.2007.00329.x","article-title":"The role of nitric oxide in inflammatory reactions","volume":"51","author":"Tripathi","year":"2007","journal-title":"FEMS Immunol. Med. Microbiol."},{"key":"ref_178","doi-asserted-by":"crossref","first-page":"427","DOI":"10.1007\/s00281-022-00961-5","article-title":"Role of alarmins in poststroke inflammation and neuronal repair","volume":"45","author":"Sakai","year":"2023","journal-title":"Semin. Immunopathol."},{"key":"ref_179","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1038\/s41435-023-00198-8","article-title":"Role of DAMPs and cell death in autoimmune diseases: The example of multiple sclerosis","volume":"24","author":"Land","year":"2023","journal-title":"Genes. Immun."},{"key":"ref_180","doi-asserted-by":"crossref","unstructured":"Kunze, R., Fischer, S., Marti, H.H., and Preissner, K.T. (2023). Brain alarm by self-extracellular nucleic acids: From neuroinflammation to neurodegeneration. J. Biomed. Sci., 30.","DOI":"10.1186\/s12929-023-00954-y"},{"key":"ref_181","doi-asserted-by":"crossref","unstructured":"Moriyama, K., and Nishida, O. (2021). Targeting Cytokines, Pathogen-Associated Molecular Patterns, and Damage-Associated Molecular Patterns in Sepsis via Blood Purification. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22168882"},{"key":"ref_182","doi-asserted-by":"crossref","first-page":"106","DOI":"10.1111\/j.1600-065X.2008.00734.x","article-title":"Function of Nod-like receptors in microbial recognition and host defense","volume":"227","author":"Franchi","year":"2009","journal-title":"Immunol. Rev."},{"key":"ref_183","doi-asserted-by":"crossref","first-page":"136","DOI":"10.1002\/path.2271","article-title":"Nod-like proteins in inflammation and disease","volume":"214","author":"Carneiro","year":"2008","journal-title":"J. Pathol."},{"key":"ref_184","doi-asserted-by":"crossref","first-page":"437","DOI":"10.1146\/annurev-med-050715-104343","article-title":"Innate Immunity and Neurodegeneration","volume":"69","author":"Labzin","year":"2018","journal-title":"Annu. Rev. Med."},{"key":"ref_185","doi-asserted-by":"crossref","first-page":"35","DOI":"10.3892\/ijmm.2023.5238","article-title":"Inhibitors of the NLRP3 inflammasome pathway as promising therapeutic candidates for inflammatory diseases (Review)","volume":"51","author":"Zhang","year":"2023","journal-title":"Int. J. Mol. Med."},{"key":"ref_186","doi-asserted-by":"crossref","first-page":"153","DOI":"10.1038\/nature18629","article-title":"Inflammasome-activated gasdermin D causes pyroptosis by forming membrane pores","volume":"535","author":"Liu","year":"2016","journal-title":"Nature"},{"key":"ref_187","doi-asserted-by":"crossref","first-page":"857","DOI":"10.1038\/ni.1636","article-title":"The NALP3 inflammasome is involved in the innate immune response to amyloid-beta","volume":"9","author":"Halle","year":"2008","journal-title":"Nat. Immunol."},{"key":"ref_188","doi-asserted-by":"crossref","first-page":"669","DOI":"10.1038\/s41586-019-1769-z","article-title":"NLRP3 inflammasome activation drives tau pathology","volume":"575","author":"Ising","year":"2019","journal-title":"Nature"},{"key":"ref_189","doi-asserted-by":"crossref","first-page":"570711","DOI":"10.3389\/fneur.2020.570711","article-title":"The Role of Microglia and the Nlrp3 Inflammasome in Alzheimer\u2019s Disease","volume":"11","author":"Hanslik","year":"2020","journal-title":"Front. Neurol."},{"key":"ref_190","doi-asserted-by":"crossref","first-page":"787","DOI":"10.4049\/jimmunol.0901363","article-title":"Cutting edge: NF-kappaB activating pattern recognition and cytokine receptors license NLRP3 inflammasome activation by regulating NLRP3 expression","volume":"183","author":"Bauernfeind","year":"2009","journal-title":"J. Immunol."},{"key":"ref_191","doi-asserted-by":"crossref","first-page":"306","DOI":"10.1016\/j.bbi.2016.12.014","article-title":"Inhibiting the NLRP3 inflammasome with MCC950 promotes non-phlogistic clearance of amyloid-beta and cognitive function in APP\/PS1 mice","volume":"61","author":"Dempsey","year":"2017","journal-title":"Brain Behav. Immun."},{"key":"ref_192","doi-asserted-by":"crossref","first-page":"786","DOI":"10.1126\/science.1232458","article-title":"Cyclic GMP-AMP synthase is a cytosolic DNA sensor that activates the type I interferon pathway","volume":"339","author":"Sun","year":"2013","journal-title":"Science"},{"key":"ref_193","doi-asserted-by":"crossref","first-page":"380","DOI":"10.1038\/nature12306","article-title":"cGAS produces a 2\u2032-5\u2032-linked cyclic dinucleotide second messenger that activates STING","volume":"498","author":"Ablasser","year":"2013","journal-title":"Nature"},{"key":"ref_194","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1016\/j.molcel.2013.01.039","article-title":"STING recognition of cytoplasmic DNA instigates cellular defense","volume":"50","author":"Abe","year":"2013","journal-title":"Mol. Cell"},{"key":"ref_195","doi-asserted-by":"crossref","first-page":"374","DOI":"10.1038\/s41586-023-06373-1","article-title":"cGAS-STING drives ageing-related inflammation and neurodegeneration","volume":"620","author":"Gulen","year":"2023","journal-title":"Nature"},{"key":"ref_196","first-page":"109","article-title":"A rat model of ataxia-telangiectasia: Evidence for a neurodegenerative phenotype","volume":"26","author":"Quek","year":"2017","journal-title":"Hum. Mol. Genet."},{"key":"ref_197","doi-asserted-by":"crossref","first-page":"R730","DOI":"10.1016\/j.cub.2022.05.027","article-title":"cGAS-STING signaling","volume":"32","author":"Sun","year":"2022","journal-title":"Curr. Biol."},{"key":"ref_198","doi-asserted-by":"crossref","first-page":"726","DOI":"10.1016\/j.tips.2022.05.004","article-title":"Toll-like receptor-mediated neuroinflammation: Relevance for cognitive dysfunctions","volume":"43","author":"Squillace","year":"2022","journal-title":"Trends Pharmacol. Sci."},{"key":"ref_199","doi-asserted-by":"crossref","unstructured":"Frederiksen, H.R., Haukedal, H., and Freude, K. (2019). Cell Type Specific Expression of Toll-Like Receptors in Human Brains and Implications in Alzheimer\u2019s Disease. Biomed. Res. Int., 2019.","DOI":"10.1155\/2019\/7420189"},{"key":"ref_200","doi-asserted-by":"crossref","first-page":"3651","DOI":"10.1074\/jbc.M508125200","article-title":"Activation of Toll-like receptor 2 on microglia promotes cell uptake of Alzheimer disease-associated amyloid beta peptide","volume":"281","author":"Chen","year":"2006","journal-title":"J. Biol. Chem."},{"key":"ref_201","doi-asserted-by":"crossref","first-page":"3281","DOI":"10.4049\/jimmunol.1600873","article-title":"Stimulation of TLR4 Attenuates Alzheimer\u2019s Disease-Related Symptoms and Pathology in Tau-Transgenic Mice","volume":"197","author":"Qin","year":"2016","journal-title":"J. Immunol."},{"key":"ref_202","doi-asserted-by":"crossref","first-page":"6539","DOI":"10.1007\/s12035-019-1540-3","article-title":"Dysregulation of TLR5 and TAM Ligands in the Alzheimer\u2019s Brain as Contributors to Disease Progression","volume":"56","author":"Santarelli","year":"2019","journal-title":"Mol. Neurobiol."},{"key":"ref_203","doi-asserted-by":"crossref","unstructured":"Chen, Y.C., Yip, P.K., Huang, Y.L., Sun, Y., Wen, L.L., Chu, Y.M., and Chen, T.F. (2012). Sequence variants of toll like receptor 4 and late-onset Alzheimer\u2019s disease. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0050771"},{"key":"ref_204","doi-asserted-by":"crossref","first-page":"458","DOI":"10.2174\/156720512800492495","article-title":"Common variants in toll-like receptor 4 confer susceptibility to Alzheimer\u2019s disease in a Han Chinese population","volume":"9","author":"Yu","year":"2012","journal-title":"Curr. Alzheimer Res."},{"key":"ref_205","first-page":"56","article-title":"Rhinotillexomania: Psychiatric disorder or habit?","volume":"56","author":"Jefferson","year":"1995","journal-title":"J. Clin. Psychiatry"},{"key":"ref_206","doi-asserted-by":"crossref","first-page":"426","DOI":"10.4088\/JCP.v62n0605","article-title":"A preliminary survey of rhinotillexomania in an adolescent sample","volume":"62","author":"Andrade","year":"2001","journal-title":"J. Clin. Psychiatry"},{"key":"ref_207","doi-asserted-by":"crossref","first-page":"989","DOI":"10.1017\/S002221510014784X","article-title":"Aetiological evaluation of foreign bodies in the ear and nose","volume":"98","author":"Das","year":"1984","journal-title":"J. Laryngol. Otol."},{"key":"ref_208","doi-asserted-by":"crossref","first-page":"863","DOI":"10.1086\/506401","article-title":"Nose picking and nasal carriage of Staphylococcus aureus","volume":"27","author":"Wertheim","year":"2006","journal-title":"Infect. Control Hosp. Epidemiol."},{"key":"ref_209","doi-asserted-by":"crossref","first-page":"e134","DOI":"10.1097\/IOP.0b013e318281eb40","article-title":"Rhinotillexomania: A rare cause of medial orbital wall erosion","volume":"29","author":"Rathore","year":"2013","journal-title":"Ophthalmic Plast. Reconstr. Surg."},{"key":"ref_210","first-page":"e9856","article-title":"Chronic Rhinotillexomania Leading to Multiple Infectious Sequelae in a 66-Year-Old Female","volume":"12","author":"Shah","year":"2020","journal-title":"Cureus"},{"key":"ref_211","doi-asserted-by":"crossref","unstructured":"Lavell, A.H.A., Tijdink, J., Buis, D.T.P., Smulders, Y.M., Bomers, M.K., and Sikkens, J.J. (2023). Why not to pick your nose: Association between nose picking and SARS-CoV-2 incidence, a cohort study in hospital health care workers. PLoS ONE, 18.","DOI":"10.1371\/journal.pone.0288352"},{"key":"ref_212","doi-asserted-by":"crossref","first-page":"429","DOI":"10.1017\/S0033291700030373","article-title":"Environmental risk factors for Alzheimer\u2019s disease: Their relationship to age of onset and to familial or sporadic types","volume":"22","author":"Henderson","year":"1992","journal-title":"Psychol. Med."}],"container-title":["Biomolecules"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2218-273X\/13\/11\/1568\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T21:10:47Z","timestamp":1760130647000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2218-273X\/13\/11\/1568"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,10,24]]},"references-count":212,"journal-issue":{"issue":"11","published-online":{"date-parts":[[2023,11]]}},"alternative-id":["biom13111568"],"URL":"https:\/\/doi.org\/10.3390\/biom13111568","relation":{},"ISSN":["2218-273X"],"issn-type":[{"value":"2218-273X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,10,24]]}}}