{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,29]],"date-time":"2026-06-29T07:48:48Z","timestamp":1782719328852,"version":"3.54.5"},"reference-count":95,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2026,6,29]],"date-time":"2026-06-29T00:00:00Z","timestamp":1782691200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Neurology International"],"abstract":"<jats:p>Background\/Objectives: Herpesviridae have been increasingly investigated as possible contributors to Alzheimer\u2019s disease (AD) because of their neurotropism, lifelong latency, and capacity to modulate inflammatory and amyloid-related pathways Methods: This structured narrative review, based on a systematic literature search, examined original studies published between December 2020 and December 2025 on the association between human herpesviridae and AD. Searches were conducted in PubMed, Web of Science, and Scopus using a PRISMA-informed screening framework. Results: The available evidence was heterogeneous across viruses and study designs. HSV-1 emerged as the most consistently implicated virus, supported by epidemiological, biomarker, neuroimaging, and experimental studies, although contradictory findings were also reported. VZV was mainly associated with AD through vascular, inflammatory, and vaccination-related evidence, with several studies suggesting lower dementia risk after zoster vaccination. CMV, EBV, and HHV-6 showed biologically plausible but less consistent associations, whereas HHV-7 and HHV-8 were supported only by limited or indirect evidence. Across studies, the proposed mechanisms included chronic neuroinflammation, vascular injury, amyloid and tau dysregulation, host immune responses, and cumulative infectious burden. Conclusions: Overall, the literature suggests that the relationship between herpesviridae and AD is not uniform and that HSV-1 appears to be the most relevant candidate. However, methodological heterogeneity, possible reverse causation, and unequal study intensity across viruses limit firm conclusions. More robust longitudinal and subtype-specific studies are needed to clarify causal relevance.<\/jats:p>","DOI":"10.3390\/neurolint18070125","type":"journal-article","created":{"date-parts":[[2026,6,29]],"date-time":"2026-06-29T05:49:33Z","timestamp":1782712173000},"page":"125","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Recent Insights into the Role of Herpesviridae in Alzheimer\u2019s Disease: A Structured Narrative Review Based on a Systematic Literature Search"],"prefix":"10.3390","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6666-7244","authenticated-orcid":false,"given":"Domenico","family":"Plantone","sequence":"first","affiliation":[{"name":"Department of Medicine, Surgery and Neuroscience, University of Siena, 53100 Siena, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4572-2616","authenticated-orcid":false,"given":"Carlo","family":"Manco","sequence":"additional","affiliation":[{"name":"Department of Medicine, Surgery and Neuroscience, University of Siena, 53100 Siena, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-3352-5618","authenticated-orcid":false,"given":"Delia","family":"Righi","sequence":"additional","affiliation":[{"name":"Department of Medicine, Surgery and Neuroscience, University of Siena, 53100 Siena, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefania","family":"Lago","sequence":"additional","affiliation":[{"name":"Department of Medicine, Surgery and Neuroscience, University of Siena, 53100 Siena, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alessio Rocco","family":"Sangiorgio","sequence":"additional","affiliation":[{"name":"Department of Medicine, Surgery and Neuroscience, University of Siena, 53100 Siena, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-0930-3881","authenticated-orcid":false,"given":"Valentina","family":"Schino","sequence":"additional","affiliation":[{"name":"Interdisciplinary Department of Medicine, Section of Occupational Medicine, University of Bari Aldo Moro, 70100 Bari, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matteo","family":"Pardini","sequence":"additional","affiliation":[{"name":"Department of Neuroscience, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health (DINOGMI), University of Genoa, 16100 Genoa, Italy"},{"name":"IRCCS Azienda Ospedaliera Metropolitana, Polo Ospedale San Martino, 16100 Genoa, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Angela","family":"Stufano","sequence":"additional","affiliation":[{"name":"Department of Medical and Surgical Sciences, University of Foggia, 71100 Foggia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1809-6376","authenticated-orcid":false,"given":"Guglielmo","family":"Lucchese","sequence":"additional","affiliation":[{"name":"Department of Experimental Medicine, University of Salento, 73100 Lecce, Italy"},{"name":"Neurology Unit, \u201cVito Fazzi\u201d Hospital, 73100 Lecce, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,6,29]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"214","DOI":"10.2174\/1570163811666140212112300","article-title":"Single Amino Acid Repeats Connect Viruses to Neurodegeneration","volume":"11","author":"Lucchese","year":"2014","journal-title":"Curr. Drug Discov. Technol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"e200460","DOI":"10.1212\/NXI.0000000000200460","article-title":"Epstein-Barr Virus in Multiple Sclerosis","volume":"12","author":"Wahbeh","year":"2025","journal-title":"Neurol. Neuroimmunol. Neuroinflamm."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"205","DOI":"10.1111\/2049-632X.12066","article-title":"Peptide matching between Epstein-Barr virus and human proteins","volume":"69","author":"Capone","year":"2013","journal-title":"Pathog. Dis."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1038\/s41579-022-00770-5","article-title":"Epstein\u2013Barr virus and multiple sclerosis","volume":"21","author":"Soldan","year":"2022","journal-title":"Nat. Rev. Microbiol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1111\/j.1532-5415.2006.01001.x","article-title":"Viral Infection and Cognitive Decline","volume":"55","author":"Itzhaki","year":"2007","journal-title":"J. Am. Geriatr. Soc."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"312","DOI":"10.1016\/S0966-842X(03)00146-X","article-title":"Do infectious agents play a role in dementia?","volume":"11","author":"Dobson","year":"2003","journal-title":"Trends Microbiol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1007\/s00406-021-01286-4","article-title":"Cognitive decline following acute viral infections: Literature review and projections for post-COVID-19","volume":"272","author":"Damiano","year":"2021","journal-title":"Eur. Arch. Psychiatry Clin. Neurosci."},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Vogelgesang, A., Steinmetz, A., Stufano, A., Schino, V., Plantone, D., Fl\u00f6el, A., and Lucchese, G. (2025). Anti-neuronal and anti-mitochondrial autoantibodies are associated with lower functional status and more severe respiratory symptoms in post COVID syndrome. Front. Immunol., 16.","DOI":"10.3389\/fimmu.2025.1642250"},{"key":"ref_9","first-page":"140539","article-title":"Alzheimer\u2019s Disease: A Pathogenetic Autoimmune Disorder Caused by Herpes Simplex in a Gene-Dependent Manner","volume":"2010","author":"Carter","year":"2010","journal-title":"Int. J. Alzheimer\u2019s Dis."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"319","DOI":"10.3233\/JAD-142853","article-title":"Herpes Simplex Virus Type 1 and Other Pathogens are Key Causative Factors in Sporadic Alzheimer\u2019s Disease","volume":"48","author":"Harris","year":"2015","journal-title":"J. Alzheimer\u2019s Dis."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1841","DOI":"10.3233\/JAD-230718","article-title":"Herpes Simplex Viral Infection Doubles the Risk of Dementia in a Contemporary Cohort of Older Adults: A Prospective Study","volume":"97","author":"Vestin","year":"2024","journal-title":"J. Alzheimer\u2019s Dis."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"414","DOI":"10.1038\/s41398-021-01532-2","article-title":"Herpes simplex virus, early neuroimaging markers and incidence of Alzheimer\u2019s disease","volume":"11","author":"Linard","year":"2021","journal-title":"Transl. Psychiatry"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"e093946","DOI":"10.1136\/bmjopen-2024-093946","article-title":"Association between herpes simplex virus type 1 and the risk of Alzheimer\u2019s disease: A retrospective case\u2013control study","volume":"15","author":"Liu","year":"2025","journal-title":"BMJ Open"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"e31116","DOI":"10.1097\/MD.0000000000031116","article-title":"Increased incidence of dementia following herpesvirus infection in the Korean population","volume":"101","author":"Shim","year":"2022","journal-title":"Medicine"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"393","DOI":"10.1177\/13872877251317228","article-title":"Increased risk of dementia associated with herpes simplex virus infections: Evidence from a retrospective cohort study using U.S. electronic health records","volume":"104","author":"Araya","year":"2025","journal-title":"J. Alzheimer\u2019s Dis."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1186\/s13195-024-01418-7","article-title":"The associations of herpes simplex virus and varicella zoster virus infection with dementia: A nationwide retrospective cohort study","volume":"16","author":"Shin","year":"2024","journal-title":"Alzheimer\u2019s Res. Ther."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"68","DOI":"10.1186\/s13195-024-01437-4","article-title":"Human in vivo evidence of associations between herpes simplex virus and cerebral amyloid-beta load in normal aging","volume":"16","author":"Cantero","year":"2024","journal-title":"Alzheimer\u2019s Res. Ther."},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Mekli, K., Lophatananon, A., Cant, R., Burns, A., Dobson, C.B., Itzhaki, R.F., and Muir, K.R. (2022). Investigation of the association between the antibody responses to neurotropic viruses and dementia outcomes in the UK Biobank. PLoS ONE, 17.","DOI":"10.1371\/journal.pone.0274872"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"253","DOI":"10.1002\/alz.13414","article-title":"DNA from multiple viral species is associated with Alzheimer\u2019s disease risk","volume":"20","author":"Tejeda","year":"2023","journal-title":"Alzheimer\u2019s Dement."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"6468","DOI":"10.1002\/alz.14141","article-title":"Infection burden, periodontal pathogens, and their interactive association with incident all-cause and Alzheimer\u2019s disease dementia in a large national survey","volume":"20","author":"Beydoun","year":"2024","journal-title":"Alzheimer\u2019s Dement."},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Olsson, J., Nourmohammadi, S., Honkala, E., Johansson, A., Hallmans, G., Weidung, B., L\u00f6vheim, H., and Elgh, F. (2024). Time trends in herpesvirus seroepidemiology among Swedish adults. BMC Infect. Dis., 24.","DOI":"10.1186\/s12879-024-09155-w"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"25424823251361066","DOI":"10.1177\/25424823251361066","article-title":"The association of specific and cumulative exposure to infectious agents with cognitive impairment in older Hispanic adults","volume":"9","author":"Rangel","year":"2025","journal-title":"J. Alzheimer\u2019s Dis. Rep."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"120856","DOI":"10.1016\/j.jns.2023.120856","article-title":"Herpes simplex virus 2 serology is associated with thinner whole-brain cortex in community-dwelling older adults","volume":"454","author":"Roberts","year":"2023","journal-title":"J. Neurol. Sci."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"229","DOI":"10.3233\/ADR-210008","article-title":"Plasma Amyloid-\u03b2 in Relation to Antibodies Against Herpes Simplex Virus, Cytomegalovirus, and Chlamydophila pneumoniae","volume":"5","author":"Weidung","year":"2021","journal-title":"J. Alzheimer\u2019s Dis. Rep."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"171","DOI":"10.3233\/JAD-230746","article-title":"Herpes Simplex Virus 1 Infection Does Not Increase Amyloid-\u03b2 Pathology in APP\/PS1 Mice","volume":"97","author":"Lapeyre","year":"2024","journal-title":"J. Alzheimer\u2019s Dis."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"e13116","DOI":"10.1111\/bpa.13116","article-title":"A\u03b2 plaques do not protect against HSV-1 infection in a mouse model of familial Alzheimer\u2019s disease, and HSV-1 does not induce A\u03b2 pathology in a model of late onset Alzheimer\u2019s disease","volume":"33","author":"Bocharova","year":"2022","journal-title":"Brain Pathol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"e13044","DOI":"10.1111\/bpa.13044","article-title":"No evidence of aberrant amyloid \u03b2 and phosphorylated tau expression in herpes simplex virus-infected neurons of the trigeminal ganglia and brain","volume":"32","author":"Tran","year":"2021","journal-title":"Brain Pathol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"100845","DOI":"10.1016\/j.jbc.2021.100845","article-title":"Alzheimer\u2019s disease-associated \u03b2-amyloid does not protect against herpes simplex virus 1 infection in the mouse brain","volume":"297","author":"Bocharova","year":"2021","journal-title":"J. Biol. Chem."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"511","DOI":"10.1001\/jama.2025.21738","article-title":"Valacyclovir Treatment of Early Symptomatic Alzheimer Disease","volume":"335","author":"Devanand","year":"2026","journal-title":"JAMA"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"791","DOI":"10.3233\/JAD-240391","article-title":"Cross-Sectional and Longitudinal Associations Between Treatment for Herpes Virus Infection and the Dispensing of Antidementia Medicines: An Analysis of the Australian Pharmaceutical Benefits Scheme Database","volume":"100","author":"Tan","year":"2024","journal-title":"J. Alzheimer\u2019s Dis."},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Sundstrom, J., Vanderleeden, E., Barton, N.J., Redick, S.D., Dawes, P., Murray, L.F., Olson, M.N., Tran, K., Chigas, S.M., and Orszulak, A.R. (2024). Herpes Simplex Virus 1 Infection of Human Brain Organoids and Pancreatic Stem Cell-Islets Drives Organoid-Specific Transcripts Associated with Alzheimer\u2019s Disease and Autoimmune Diseases. Cells, 13.","DOI":"10.20944\/preprints202407.1267.v1"},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Qiao, H., Zhao, W., Guo, M., Zhu, L., Chen, T., Wang, J., Xu, X., Zhang, Z., Wu, Y., and Chen, P. (2022). Cerebral Organoids for Modeling of HSV-1-Induced-Amyloid \u03b2 Associated Neuropathology and Phenotypic Rescue. Int. J. Mol. Sci., 23.","DOI":"10.1101\/2022.02.11.480178"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1284","DOI":"10.1093\/infdis\/jiaa513","article-title":"Amylin, A\u03b242, and Amyloid in Varicella Zoster Virus Vasculopathy Cerebrospinal Fluid and Infected Vascular Cells","volume":"223","author":"Bubak","year":"2020","journal-title":"J. Infect. Dis."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"e1103","DOI":"10.1212\/NXI.0000000000001103","article-title":"Targeted RNA Sequencing of VZV-Infected Brain Vascular Adventitial Fibroblasts Indicates That Amyloid May Be Involved in VZV Vasculopathy","volume":"9","author":"Bubak","year":"2022","journal-title":"Neurol. Neuroimmunol. Neuroinflamm."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1186\/s40035-020-00227-w","article-title":"Cerebral spinal fluid biomarker profiles in CNS infection associated with HSV and VZV mimic patterns in Alzheimer\u2019s disease","volume":"10","author":"Shinomoto","year":"2021","journal-title":"Transl. Neurodegener."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"22400","DOI":"10.1038\/s41598-020-79800-2","article-title":"Cognitive impairment without altered levels of cerebrospinal fluid biomarkers in patients with encephalitis caused by varicella-zoster virus: A pilot study","volume":"10","author":"Nilsson","year":"2020","journal-title":"Sci. Rep."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"25475","DOI":"10.1038\/s41598-025-10102-1","article-title":"Human herpes viruses are associated with steeper age-dependent increases of serum biomarkers for dementia in cognitively unimpaired women","volume":"15","author":"James","year":"2025","journal-title":"Sci. Rep."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"e045871","DOI":"10.1136\/bmjopen-2020-045871","article-title":"Shingles, Zostavax vaccination and risk of developing dementia: A nested case\u2013control study\u2014Results from the UK Biobank cohort","volume":"11","author":"Lophatananon","year":"2021","journal-title":"BMJ Open"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"4841","DOI":"10.1002\/alz.13070","article-title":"Association of common infections with cognitive performance in the Baltimore Epidemiologic Catchment Area study follow-up","volume":"19","author":"Wennberg","year":"2023","journal-title":"Alzheimer\u2019s Dement."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"15333175211006504","DOI":"10.1177\/15333175211006504","article-title":"Herpes Zoster Does Not Increase the Risk of Neurodegenerative Dementia: A Case-Control Study","volume":"36","author":"Choi","year":"2021","journal-title":"Am. J. Alzheimer\u2019s Dis. Other Dement."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"180","DOI":"10.1186\/s13195-024-01511-x","article-title":"Herpes zoster and long-term risk of subjective cognitive decline","volume":"16","author":"Yeh","year":"2024","journal-title":"Alzheimer\u2019s Res. Ther."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"3271","DOI":"10.21873\/invivo.12622","article-title":"Herpes Zoster Vaccination Reduces Risk of Dementia","volume":"35","author":"Lehrer","year":"2021","journal-title":"Vivo"},{"key":"ref_43","doi-asserted-by":"crossref","unstructured":"Lophatananon, A., Carr, M., Mcmillan, B., Dobson, C., Itzhaki, R., Parisi, R., Ashcroft, D.M., and Muir, K.R. (2023). The association of herpes zoster and influenza vaccinations with the risk of developing dementia: A population-based cohort study within the UK Clinical Practice Research Datalink. BMC Public Health, 23.","DOI":"10.1186\/s12889-023-16768-4"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"7049","DOI":"10.1016\/j.cell.2025.11.007","article-title":"The effect of shingles vaccination at different stages of the dementia disease course","volume":"188","author":"Xie","year":"2025","journal-title":"Cell"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"703","DOI":"10.3233\/JAD-221231","article-title":"The Impact of Routine Vaccinations on Alzheimer\u2019s Disease Risk in Persons 65 Years and Older: A Claims-Based Cohort Study Using Propensity Score Matching","volume":"95","author":"Harris","year":"2023","journal-title":"J. Alzheimer\u2019s Dis."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"138192","DOI":"10.1016\/j.neulet.2025.138192","article-title":"Studying the effect of Chlamydia trachomatis, Helicobacter pylori, and Varicella zoster microorganisms in stimulating the expression of cytokines TNF\u03b1, IFN\u03b3, TGF\u03b2, IL-10 in Alzheimer and non-Alzheimer patients","volume":"852","author":"Taheri","year":"2025","journal-title":"Neurosci. Lett."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1186\/s41065-024-00358-4","article-title":"Alzheimer\u2019s disease and antibody-mediated immune responses to infectious diseases agents: A mendelian randomization study","volume":"162","author":"Zhang","year":"2025","journal-title":"Hereditas"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"158","DOI":"10.1186\/s13195-021-00905-5","article-title":"Herpesvirus infections and Alzheimer\u2019s disease: A Mendelian randomization study","volume":"13","author":"Huang","year":"2021","journal-title":"Alzheimer\u2019s Res. Ther."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"e44145","DOI":"10.1097\/MD.0000000000044145","article-title":"Causal effect of infectious mononucleosis on neurodegenerative diseases: A Mendelian randomization study","volume":"104","author":"Peng","year":"2025","journal-title":"Medicine"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"122","DOI":"10.1016\/j.neurobiolaging.2013.06.024","article-title":"Herpes virus in Alzheimer\u2019s disease: Relation to progression of the disease","volume":"35","author":"Carbone","year":"2014","journal-title":"Neurobiol. Aging"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"102462","DOI":"10.1016\/j.jiph.2024.05.050","article-title":"Alzheimer\u2019s disease risk associated with changes in Epstein-Barr virus nuclear antigen 1-specific epitope targeting antibody levels","volume":"17","author":"Sim","year":"2024","journal-title":"J. Infect. Public Health"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"S128","DOI":"10.1093\/infdis\/jiae242","article-title":"From Viral Infections to Alzheimer\u2019s Disease: Unveiling the Mechanistic Links Through Systems Bioinformatics","volume":"230","author":"Onisiforou","year":"2024","journal-title":"J. Infect. Dis."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"eadt7176","DOI":"10.1126\/sciadv.adt7176","article-title":"Proteomic signatures of corona and herpes viral antibodies identify IGDCC4 as a mediator of neurodegeneration","volume":"11","author":"Duggan","year":"2025","journal-title":"Sci. Adv."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"679","DOI":"10.1097\/PSY.0000000000001080","article-title":"Diminished Cellular Immunity and Executive Cognitive Functioning Among Middle-Aged and Elderly Adults","volume":"84","author":"Murdock","year":"2022","journal-title":"Psychosom. Med."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"8918","DOI":"10.1080\/07391102.2022.2138978","article-title":"An in-silico insight into the predictive interaction of Apolipoprotein-E with Epstein-Barr virus proteins and their probable role in mediating Alzheimer\u2019s disease","volume":"41","author":"Tiwari","year":"2022","journal-title":"J. Biomol. Struct. Dyn."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"3957","DOI":"10.1021\/acschemneuro.1c00584","article-title":"Indication of Neurodegenerative Cascade Initiation by Amyloid-like Aggregate-Forming EBV Proteins and Peptide in Alzheimer\u2019s Disease","volume":"12","author":"Tiwari","year":"2021","journal-title":"ACS Chem. Neurosci."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"2450","DOI":"10.1021\/acschemneuro.3c00231","article-title":"Unraveling the Connection of Epstein\u2013Barr Virus and Its Glycoprotein M146\u2013157 Peptide with Neurological Ailments","volume":"14","author":"Patra","year":"2023","journal-title":"ACS Chem. Neurosci."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"e202200527","DOI":"10.1002\/cbdv.202200527","article-title":"Targeting Epstein-Barr Virus dUTPase, an Immunomodulatory Protein Using Antiviral, Anti-Inflammatory, and Neuroprotective Phytochemicals","volume":"19","author":"Tiwari","year":"2022","journal-title":"Chem. Biodivers."},{"key":"ref_59","doi-asserted-by":"crossref","unstructured":"Awasthi, P., Kumar, D., and Hasan, S. (2024). Role of 14-3-3 protein family in the pathobiology of EBV in immortalized B cells and Alzheimer\u2019s disease. Front. Mol. Biosci., 11.","DOI":"10.3389\/fmolb.2024.1353828"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"805","DOI":"10.15789\/1563-0625-HIA-2168","article-title":"Herpesvirus Infections and Clinical-Immunologic Interactions in Patients with Early-Onset Alzheimer\u2019s Disease and Late-Onset Alzheimer\u2019s Disease","volume":"23","author":"Malashenkova","year":"2021","journal-title":"Med. Immunol."},{"key":"ref_61","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_62","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_63","doi-asserted-by":"crossref","first-page":"129","DOI":"10.36233\/0507-4088-32","article-title":"Herpesvirus infections and immunological disturbances in patients with different stages of Alzheimer\u2019s disease","volume":"66","author":"Krynskiy","year":"2021","journal-title":"Probl. Virol."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"593","DOI":"10.3233\/JAD-230220","article-title":"Anti-CMV IgG Seropositivity is Associated with Plasma Biomarker Evidence of Amyloid-\u03b2 Accumulation","volume":"98","author":"Parker","year":"2024","journal-title":"J. Alzheimer\u2019s Dis."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"2560904","DOI":"10.1080\/21505594.2025.2560904","article-title":"Exploring the role of multi-pathogen infections in Alzheimer\u2019s disease: A case\u2013control study","volume":"16","author":"Baquero","year":"2025","journal-title":"Virulence"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"1331","DOI":"10.1007\/s12035-023-03553-y","article-title":"Single-Cell RNA Sequencing Transcriptomics Revealed CMV IE2-Related Microglia Responses in Alzheimer\u2019s-like Disease in Transgenic Mice","volume":"61","author":"Liu","year":"2023","journal-title":"Mol. Neurobiol."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"169","DOI":"10.1186\/s12985-025-02786-8","article-title":"Oxidative stress, inflammation, and apoptosis in Alzheimer\u2019s disease associated with HSV-1 and CMV coinfection","volume":"22","author":"Khodamoradi","year":"2025","journal-title":"Virol. J."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"26331055241258436","DOI":"10.1177\/26331055241258436","article-title":"Negative Association of Cognitive Performance with Blood Serum Neurotoxicity and Its Modulation by Human Herpes Virus 5 (HHV5) Seropositivity in Healthy Women","volume":"19","author":"James","year":"2024","journal-title":"Neurosci. Insights"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"786","DOI":"10.1093\/aje\/kwaa238","article-title":"Association Between Immune Response to Cytomegalovirus and Cognition in the Health and Retirement Study","volume":"190","author":"Stebbins","year":"2020","journal-title":"Am. J. Epidemiol."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"e70457","DOI":"10.1002\/alz.70457","article-title":"The association of common infectious exposures with cognitive performance in community-dwelling older adults","volume":"21","author":"Roberts","year":"2025","journal-title":"Alzheimer\u2019s Dement."},{"key":"ref_71","doi-asserted-by":"crossref","unstructured":"Vacher, M., Lee, S., Price, P., Ha, P., Waters, S., and Laws, S.M. (2025). Relationship between cytomegalovirus antibody levels and cognitive performance is dependent on age and genetic risk. BMC Neurol., 25.","DOI":"10.1186\/s12883-025-04279-1"},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"155","DOI":"10.1016\/j.bbi.2024.07.026","article-title":"Specific and cumulative infection burden and mild cognitive impairment and dementia: A population-based study","volume":"121","author":"Shi","year":"2024","journal-title":"Brain Behav. Immun."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"105414","DOI":"10.1016\/j.psyneuen.2021.105414","article-title":"Immune function, cortisol, and cognitive decline & dementia in an aging latino population","volume":"133","author":"Stebbins","year":"2021","journal-title":"Psychoneuroendocrinology"},{"key":"ref_74","first-page":"81","article-title":"Cross sectional association between cytomegalovirus seropositivity, inflammation and cognitive impairment in elderly cancer survivors","volume":"33","author":"Vivek","year":"2021","journal-title":"Cancer Causes Control"},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"593","DOI":"10.3233\/JAD-200957","article-title":"Herpes Labialis, Chlamydophila pneumoniae, Helicobacter pylori, and Cytomegalovirus Infections and Risk of Dementia: The Framingham Heart Study","volume":"82","author":"Zilli","year":"2021","journal-title":"J. Alzheimer\u2019s Dis."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"102757","DOI":"10.1016\/j.eclinm.2024.102757","article-title":"The association between cytomegalovirus infection and neurodegenerative diseases: A prospective cohort using UK Biobank data","volume":"74","author":"Ma","year":"2024","journal-title":"eClinicalMedicine"},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"111140","DOI":"10.1016\/j.mehy.2023.111140","article-title":"CMV as a factor in the development of Alzheimer\u2019s disease?","volume":"178","author":"Blanck","year":"2023","journal-title":"Med. Hypotheses"},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"e14401","DOI":"10.1002\/alz.14401","article-title":"Alzheimer\u2019s disease-associated CD83(+) microglia are linked with increased immunoglobulin G4 and human cytomegalovirus in the gut, vagal nerve, and brain","volume":"21","author":"Readhead","year":"2024","journal-title":"Alzheimer\u2019s Dement."},{"key":"ref_79","doi-asserted-by":"crossref","unstructured":"Agostini, S., Mancuso, R., Costa, A.S., Citterio, L.A., Guerini, F.R., Meloni, M., Navarro, J., and Clerici, M. (2021). A Possible Role for HSV-1-Specific Humoral Response and PILRA rs1859788 Polymorphism in the Pathogenesis of Parkinson\u2019s Disease. Vaccines, 9.","DOI":"10.3390\/vaccines9070686"},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"e01688-21","DOI":"10.1128\/jvi.01688-21","article-title":"Human Herpesvirus 6A U4 Inhibits Proteasomal Degradation of the Amyloid Precursor Protein","volume":"96","author":"Tang","year":"2022","journal-title":"J. Virol."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"103770","DOI":"10.1016\/j.mcn.2022.103770","article-title":"Expression of the human herpesvirus 6A latency-associated transcript U94A impairs cytoskeletal functions in human neural cells","volume":"123","author":"Hogestyn","year":"2022","journal-title":"Mol. Cell. Neurosci."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"198726","DOI":"10.1016\/j.virusres.2022.198726","article-title":"The dysregulation of autophagy and ER stress induced by HHV-6A infection activates pro-inflammatory pathways and promotes the release of inflammatory cytokines and cathepsin S by CNS cells","volume":"313","author":"Romeo","year":"2022","journal-title":"Virus Res."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1186\/s13024-021-00514-8","article-title":"Murine roseolovirus does not accelerate amyloid-\u03b2 pathology and human roseoloviruses are not over-represented in Alzheimer disease brains","volume":"17","author":"Bigley","year":"2022","journal-title":"Mol. Neurodegener."},{"key":"ref_84","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_85","doi-asserted-by":"crossref","unstructured":"Jain, N., Smirnovs, M., Strojeva, S., Murovska, M., and Skuja, S. (2021). Chronic Alcoholism and HHV-6 Infection Synergistically Promote Neuroinflammatory Microglial Phenotypes in the Substantia Nigra of the Adult Human Brain. Biomedicines, 9.","DOI":"10.3390\/biomedicines9091216"},{"key":"ref_86","doi-asserted-by":"crossref","unstructured":"Kasimir, F., Toomey, D., Liu, Z., Kaiping, A.C., Ariza, M.E., and Prusty, B.K. (2022). Tissue specific signature of HHV-6 infection in ME\/CFS. Front. Mol. Biosci., 9.","DOI":"10.3389\/fmolb.2022.1044964"},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"239","DOI":"10.1097\/QCO.0000000000000554","article-title":"Herpes simplex virus encephalitis update","volume":"32","author":"Stahl","year":"2019","journal-title":"Curr. Opin. Infect. Dis."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"92","DOI":"10.1007\/s40475-022-00255-8","article-title":"Herpesvirus-Associated Encephalitis: An Update","volume":"9","author":"Matthews","year":"2022","journal-title":"Curr. Trop. Med. Rep."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"15","DOI":"10.3390\/biophysica1010002","article-title":"A Protein Assembly Hypothesis for Population-Specific Decrease in Dementia with Time","volume":"1","author":"Serwer","year":"2021","journal-title":"Biophysica"},{"key":"ref_90","doi-asserted-by":"crossref","unstructured":"Li, Z., Martin, N.P., Epstein, J., Chen, S.-H., Hao, Y., Ramos, D.M., Andersh, K.M., Jarreau, P., Weller, C., and Nalls, M.A. (2025). Proteomic Analysis of Endemic Viral Infections in Neurons offers Insights into Neurodegenerative Diseases. openRxiv.","DOI":"10.1101\/2025.03.17.643709"},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"961","DOI":"10.3233\/JAD-240073","article-title":"Analysis of the Association Between Pathogen Exposure and the Risk of Dementia","volume":"100","author":"Fu","year":"2024","journal-title":"J. Alzheimer\u2019s Dis."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1515\/revneuro-2023-0049","article-title":"Peripheral inflammation is a potential etiological factor in Alzheimer\u2019s disease","volume":"35","author":"Li","year":"2023","journal-title":"Rev. Neurosci."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"254","DOI":"10.1016\/j.bbi.2016.07.153","article-title":"High avidity HSV-1 antibodies correlate with absence of amnestic Mild Cognitive Impairment conversion to Alzheimer\u2019s disease","volume":"58","author":"Agostini","year":"2016","journal-title":"Brain Behav. Immun."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1080\/14787210.2017.1264271","article-title":"A protective role for herpes simplex virus type-1-specific humoral immunity in Alzheimer\u2019s Disease","volume":"15","author":"Agostini","year":"2016","journal-title":"Expert Rev. Anti-Infect. Ther."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"8691","DOI":"10.1038\/s41598-021-87963-9","article-title":"Herpes simplex virus 1 and the risk of dementia: A population-based study","volume":"11","author":"Murphy","year":"2021","journal-title":"Sci. Rep."}],"container-title":["Neurology International"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2035-8377\/18\/7\/125\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,6,29]],"date-time":"2026-06-29T07:35:09Z","timestamp":1782718509000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2035-8377\/18\/7\/125"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,6,29]]},"references-count":95,"journal-issue":{"issue":"7","published-online":{"date-parts":[[2026,7]]}},"alternative-id":["neurolint18070125"],"URL":"https:\/\/doi.org\/10.3390\/neurolint18070125","relation":{},"ISSN":["2035-8377"],"issn-type":[{"value":"2035-8377","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,6,29]]}}}