{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T19:15:23Z","timestamp":1792178123618,"version":"4.4.0"},"reference-count":61,"publisher":"Frontiers Media SA","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Front. Aging Neurosci."],"DOI":"10.3389\/fnagi.2014.00202","type":"journal-article","created":{"date-parts":[[2014,8,11]],"date-time":"2014-08-11T13:11:45Z","timestamp":1407762705000},"source":"Crossref","is-referenced-by-count":185,"title":["Herpes simplex virus type 1 and Alzheimer\u00e2\u20ac\u2122s disease: increasing evidence for a major role of the virus"],"prefix":"10.3389","volume":"6","author":[{"given":"Ruth F.","family":"Itzhaki","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2014,8,11]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"529","DOI":"10.1007\/s00401-006-0037-0","article-title":"Accelerated Tau deposition in the brains of individuals infected with human immunodeficiency virus-1 before and after the advent of highly active anti-retroviral therapy","volume":"111","author":"Anthony","year":"2006","journal-title":"Acta Neuropathol."},{"key":"B2","doi-asserted-by":"publisher","first-page":"4189","DOI":"10.4049\/jimmunol.175.7.4189","article-title":"Cutting edge: TLR2-mediated proinflammatory cytokine and chemokine production by microglial cells in response to herpes simplex virus","volume":"175","author":"Aravalli","year":"2005","journal-title":"J. Immunol."},{"key":"B3","doi-asserted-by":"crossref","first-page":"303","DOI":"10.1017\/S0317167100044115","article-title":"Limbic predilection in Alzheimer dementia: is reactivated herpesvirus involved?","volume":"9","author":"Ball","year":"1982","journal-title":"Can. J. Neurol. Sci."},{"key":"B4","doi-asserted-by":"publisher","first-page":"885","DOI":"10.2217\/fvl.12.81","article-title":"HSV, axonal transport and Alzheimer\u00e2\u20ac\u2122s disease: in vitro and in vivo evidence for causal relationships","volume":"7","author":"Bearer","year":"2012","journal-title":"Future Virol."},{"key":"B5","doi-asserted-by":"publisher","first-page":"1548","DOI":"10.1128\/JVI.02972-13","article-title":"Novel treatment with neuroprotective and antiviral properties against a neuroinvasive human respiratory virus","volume":"88","author":"Brison","year":"2014","journal-title":"J. Virol."},{"key":"B6","doi-asserted-by":"publisher","first-page":"356","DOI":"10.1002\/ana.410420312","article-title":"Pathological tau proteins in postencephalitic parkinsonism: comparison with Alzheimer\u00e2\u20ac\u2122s disease and other neurodegenerative disorders","volume":"42","author":"Bu\u00c3\u00a9e-Scherrer","year":"1997","journal-title":"Ann. Neurol."},{"key":"B8","doi-asserted-by":"publisher","first-page":"1825","DOI":"10.1097\/00001756-200310060-00013","article-title":"ApoE4 is more efficient than E3 in brain access by herpes simplex virus type 1","volume":"14","author":"Burgos","year":"2003","journal-title":"Neuroreport"},{"key":"B7","doi-asserted-by":"publisher","first-page":"5383","DOI":"10.1128\/jvi.00006-06","article-title":"Effect of apolipoprotein E on the cerebral load of latent herpes simplex virus type 1 DNA","volume":"80","author":"Burgos","year":"2006","journal-title":"J. Virol."},{"key":"B9","doi-asserted-by":"publisher","first-page":"240","DOI":"10.1111\/2049-632X.12077","article-title":"Susceptibility genes are enriched in those of the herpes simplex virus 1\/host interactome in psychiatric and neurological disorders","volume":"69","author":"Carter","year":"2013","journal-title":"Pathog. Dis."},{"key":"B10","doi-asserted-by":"publisher","first-page":"e17966","DOI":"10.1371\/journal.pone.0017966","article-title":"Herpes simplex virus dances with amyloid precursor protein while exiting the cell","volume":"6","author":"Cheng","year":"2011","journal-title":"PLoS One"},{"key":"B12","doi-asserted-by":"publisher","first-page":"e13989","DOI":"10.1371\/journal.pone.0013989","article-title":"APP processing induced by herpes simplex virus type 1 (HSV-1) yields several APP fragments in human and rat neuronal cells","volume":"5","author":"De Chiara","year":"2010","journal-title":"PLoS One"},{"key":"B13","volume-title":"1879\u00e2\u20ac\u201d1970. A Biographical Memoir.","author":"Dulbecco","year":"1976"},{"key":"B14","doi-asserted-by":"publisher","first-page":"e29480","DOI":"10.1371\/journal.pone.0029480","article-title":"Association between IgM anti-herpes simplex virus and plasma amyloid-beta levels","volume":"6","author":"F\u00c3\u00a9art","year":"2011","journal-title":"PLoS One"},{"key":"B15","doi-asserted-by":"publisher","first-page":"849","DOI":"10.1093\/cid\/cit376","article-title":"Central nervous system herpes simplex and varicella zoster virus infections in natalizumab-treated patients","volume":"57","author":"Fine","year":"2013","journal-title":"Clin. Infect. Dis."},{"key":"B16","doi-asserted-by":"publisher","first-page":"247","DOI":"10.1017\/S0033291700009053","article-title":"Viruses, brain and immunosuppression","volume":"16","author":"Gannicliffe","year":"1986","journal-title":"Psychol. Med."},{"key":"B59","doi-asserted-by":"publisher","first-page":"779","DOI":"10.3233\/JAD-2012-120070","article-title":"Aging-related neurostructural, neuropathological, and behavioral changes associated with herpes simplex virus type 1 brain infection in mice","volume":"30","author":"Guzman-Sanchez","year":"2012","journal-title":"J. Alzheimers Dis."},{"key":"B60","doi-asserted-by":"publisher","first-page":"e21456","DOI":"10.1371\/journal.pone.0021456","article-title":"Activation of PKR causes amyloid \u00c3\u0178-peptide accumulation via de-repression of BACE1 expression","volume":"6","author":"Ill-Raga","year":"2011","journal-title":"PLoS One"},{"key":"B17","doi-asserted-by":"publisher","first-page":"972","DOI":"10.1093\/infdis\/jit665","article-title":"Cytomegalovirus: an improbable cause of Alzheimer disease","volume":"209","author":"Itzhaki","year":"2014","journal-title":"J. Infect. Dis."},{"key":"B18","doi-asserted-by":"publisher","first-page":"241","DOI":"10.1016\/S0140-6736(96)10149-5","article-title":"Early reports herpes simplex virus type 1 in brain and risk of Alzheimer\u00e2\u20ac\u2122s disease","volume":"349","author":"Itzhaki","year":"1997","journal-title":"Lancet"},{"key":"B58","doi-asserted-by":"publisher","first-page":"307","DOI":"10.2217\/fmb.12.10","article-title":"Could antivirals be used to treat Alzheimer\u00e2\u20ac\u2122s disease?","volume":"7","author":"Itzhaki","year":"2012","journal-title":"Future Microbiol."},{"key":"B19","doi-asserted-by":"publisher","first-page":"224","DOI":"10.1002\/jmv.1890330403","article-title":"Latent herpes simplex virus type 1 in normal and Alzheimer\u00e2\u20ac\u2122s disease brains","volume":"33","author":"Jamieson","year":"1991","journal-title":"J. Med. Virol."},{"key":"B20","doi-asserted-by":"publisher","first-page":"516","DOI":"10.1136\/sti.2008.032367","article-title":"Apolipoprotein E-\u00ce\u00b54 and recurrent genital herpes in individuals co-infected with herpes simplex virus type 2 and HIV","volume":"85","author":"Jayasuriya","year":"2008","journal-title":"Sex. Transm. Infect."},{"key":"B21","doi-asserted-by":"publisher","first-page":"1209","DOI":"10.1212\/WNL.0b013e3182896e79","article-title":"Infectious burden and cognitive function: the Northern Manhattan study","volume":"80","author":"Katan","year":"2013","journal-title":"Neurology"},{"key":"B22","doi-asserted-by":"publisher","first-page":"1247","DOI":"10.1136\/jnnp.47.11.1247","article-title":"Mild forms of herpes encephalitis","volume":"47","author":"Klapper","year":"1984","journal-title":"J. Neurol. Neurosurg. Psychiatry"},{"key":"B23","doi-asserted-by":"publisher","first-page":"907","DOI":"10.1016\/j.bbrc.2012.12.054","article-title":"Increase in the IgG avidity index due to herpes simplex virus type 1 reactivation and its relationship with cognitive function in amnestic mild cognitive impairment and Alzheimer\u00e2\u20ac\u2122s disease","volume":"430","author":"Kobayashi","year":"2013","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"B11","doi-asserted-by":"publisher","first-page":"202","DOI":"10.1136\/sti.2009.039735","article-title":"APOE genotype is associated with oral herpetic lesions but not genital or oral herpes simplex virus shedding","volume":"86","author":"Koelle","year":"2010","journal-title":"Sex. Transm. Infect."},{"key":"B24","doi-asserted-by":"publisher","first-page":"620","DOI":"10.1007\/s00415-012-6688-y","article-title":"Cerebrospinal fluid Alzheimer\u00e2\u20ac\u2122s biomarker profiles in CNS infections","volume":"260","author":"Krut","year":"2013","journal-title":"J. Neurol."},{"key":"B25","doi-asserted-by":"publisher","first-page":"4703","DOI":"10.1167\/iovs.09-4884","article-title":"Effect of high versus low oral doses of valacyclovir on herpes simplex virus-1 DNA shedding into tears of latently infected rabbits","volume":"51","author":"Kumar","year":"2010","journal-title":"Invest. Ophthalmol. Vis. Sci."},{"key":"B26","doi-asserted-by":"publisher","first-page":"513","DOI":"10.3233\/JAD-2010-101386","article-title":"Tau cleavage at D421 by caspase-3 is induced in neurons and astrocytes infected with herpes simplex virus type 1","volume":"23","author":"Lerchundi","year":"2011","journal-title":"J. Alzheimers Dis."},{"key":"B27","doi-asserted-by":"publisher","first-page":"e3637","DOI":"10.1371\/journal.pone.0003637","article-title":"Seropositivity to herpes simplex virus antibodies and risk of Alzheimer\u00e2\u20ac\u2122s disease: a population-based cohort study","volume":"3","author":"Letenneur","year":"2008","journal-title":"PLoS One"},{"key":"B28","doi-asserted-by":"publisher","first-page":"809","DOI":"10.3233\/JAD-2011-110755","article-title":"Gene signature in Alzheimer\u00e2\u20ac\u2122s disease and environmental factors: the virus chronicle","volume":"27","author":"Licastro","year":"2011","journal-title":"J. Alzheimers Dis."},{"key":"B29","doi-asserted-by":"publisher","first-page":"395","DOI":"10.1002\/path.1127","article-title":"Herpesviruses in brain and Alzheimer\u00e2\u20ac\u2122s disease","volume":"197","author":"Lin","year":"2002a","journal-title":"J. Pathol."},{"key":"B30","doi-asserted-by":"publisher","first-page":"82","DOI":"10.1006\/nbdi.2001.0465","article-title":"Cytomegalovirus is present in a very high proportion of brains from vascular dementia patients","volume":"9","author":"Lin","year":"2002b","journal-title":"Neurobiol. Dis."},{"key":"B61","doi-asserted-by":"publisher","DOI":"10.1016\/j.jalz.2014.04.522","article-title":"Reactivated herpes simplex infection increases the risk of Alzheimer\u00e2\u20ac\u2122s disease","author":"L\u00c3\u00b6vheim","year":"2014","journal-title":"Alzheimers Dement."},{"key":"B31","doi-asserted-by":"publisher","first-page":"564","DOI":"10.1093\/infdis\/jit210","article-title":"Virological and immunological characteristics of human cytomegalovirus infection associated with Alzheimer disease","volume":"208","author":"Lurain","year":"2013","journal-title":"J. Infect. Dis."},{"key":"B32","doi-asserted-by":"publisher","first-page":"741","DOI":"10.3233\/JAD-130977","article-title":"Titers of herpes simplex virus type 1 antibodies positively correlate with grey matter volumes in Alzheimer\u00e2\u20ac\u2122s disease","volume":"38","author":"Mancuso","year":"2014","journal-title":"J. Alzheimers Dis."},{"key":"B33","doi-asserted-by":"publisher","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. Alzheimers Dis."},{"key":"B34","doi-asserted-by":"publisher","first-page":"177","DOI":"10.1006\/mcpr.2001.0356","article-title":"Review of 3200 serially received CSF samples submitted for type-specific HSV detection by PCR in the reference laboratory setting","volume":"15","author":"Peter","year":"2001","journal-title":"Mol. Cell. Probes"},{"key":"B35","doi-asserted-by":"publisher","first-page":"16","DOI":"10.1186\/1742-4933-7-16","article-title":"Alzheimer\u00e2\u20ac\u2122s disease gene signature says: beware of brain viral infections","volume":"7","author":"Porcellini","year":"2010","journal-title":"Immun. Ageing"},{"key":"B36","doi-asserted-by":"publisher","first-page":"1137","DOI":"10.1093\/schbul\/sbs046","article-title":"Exposure to herpes simplex virus type 1 and cognitive impairments in individuals with schizophrenia","volume":"38","author":"Prasad","year":"2012","journal-title":"Schizophr. Bull."},{"key":"B37","doi-asserted-by":"publisher","first-page":"311","DOI":"10.1093\/ageing\/16.5.311","article-title":"A sero-epidemiological study of conventional infectious agents in Alzheimer\u00e2\u20ac\u2122s disease","volume":"16","author":"Renvoize","year":"1987","journal-title":"Age Ageing"},{"key":"B38","doi-asserted-by":"publisher","first-page":"573","DOI":"10.1007\/s40263-013-0074-x","article-title":"Synthesis and comparison of the meta-analyses evaluating the efficacy of memantine in moderate to severe stages of Alzheimer\u00e2\u20ac\u2122s disease","volume":"27","author":"Rive","year":"2013","journal-title":"CNS Drugs"},{"key":"B39","doi-asserted-by":"publisher","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":"B40","doi-asserted-by":"publisher","first-page":"305","DOI":"10.1046\/j.1474-9728.2003.00069.x","article-title":"Fast anterograde transport of herpes simplex virus: role for the amyloid precursor protein of Alzheimer\u00e2\u20ac\u2122s disease","volume":"2","author":"Satpute-Krishnan","year":"2003","journal-title":"Aging Cell"},{"key":"B41","doi-asserted-by":"publisher","first-page":"1797","DOI":"10.1002\/jmv.23397","article-title":"Reactivation of herpes simplex virus type 1 is associated with cytomegalovirus and age","volume":"84","author":"Stowe","year":"2012","journal-title":"J. Med. Virol."},{"key":"B43","doi-asserted-by":"publisher","first-page":"1001","DOI":"10.1016\/j.neurobiolaging.2004.09.008","article-title":"Interaction of herpesviridae, APOE gene and education in cognitive impairment","volume":"26","author":"Strandberg","year":"2005","journal-title":"Neurobiol. Aging"},{"key":"B42","doi-asserted-by":"publisher","first-page":"2126","DOI":"10.1161\/01.str.0000086754.32238.da","article-title":"Impact of viral and bacterial burden on cognitive impairment in elderly persons with cardiovascular diseases","volume":"34","author":"Strandberg","year":"2003","journal-title":"Stroke"},{"key":"B44","doi-asserted-by":"publisher","first-page":"2811","DOI":"10.1016\/j.ajpath.2011.02.012","article-title":"Inflammation induced by infection potentiates tau pathological features in transgenic mice","volume":"178","author":"Sy","year":"2011","journal-title":"Am. J. Pathol."},{"key":"B45","doi-asserted-by":"publisher","first-page":"837","DOI":"10.1093\/infdis\/jit616","article-title":"Persistent viral pathogens and cognitive impairment across the life course in the third national health and nutrition examination survey","volume":"209","author":"Tarter","year":"2014","journal-title":"J. Infect. Dis."},{"key":"B46","doi-asserted-by":"publisher","first-page":"289","DOI":"10.1017\/s0033291700009107","article-title":"Viruses in human brains: a search for cytomegalovirus and herpes virus 1 DNA in necropsy tissue from normal and neuropsychiatric cases","volume":"16","author":"Taylor","year":"1986","journal-title":"Psychol. Med."},{"key":"B47","doi-asserted-by":"publisher","first-page":"371","DOI":"10.1007\/s00430-012-0247-0","article-title":"Herpes simplex virus type 1 induces simultaneous activation of toll-like receptors 2 and 4 and expression of the endogenous ligand serum amyloid A in astrocytes","volume":"201","author":"Villalba","year":"2012","journal-title":"Med. Microbiol. Immunol."},{"key":"B48","doi-asserted-by":"publisher","first-page":"e96779","DOI":"10.1371\/journal.pone.0096779","article-title":"Increased inflammatory response in cytomegalovirus seropositive patients with Alzheimer\u00e2\u20ac\u2122s disease","volume":"9","author":"Westman","year":"2014","journal-title":"PLoS One"},{"key":"B49","doi-asserted-by":"publisher","first-page":"288","DOI":"10.1002\/ana.410050311","article-title":"Alzheimer neurofibrillary tangles in diseases other than senile and presenile dementia","volume":"5","author":"Wisniewski","year":"1979","journal-title":"Ann. Neurol."},{"key":"B50","doi-asserted-by":"publisher","first-page":"401","DOI":"10.1016\/j.antiviral.2013.07.003","article-title":"The helicase-primase inhibitor BAY 57\u00e2\u20ac\u201c1293 reduces the Alzheimer\u00e2\u20ac\u2122s disease-related molecules induced by herpes simplex virus type 1","volume":"99","author":"Wozniak","year":"2013a","journal-title":"Antiviral Res."},{"key":"B51","doi-asserted-by":"publisher","first-page":"e25152","DOI":"10.1371\/journal.pone.0025152","article-title":"Antivirals reduce the formation of key Alzheimer\u00e2\u20ac\u2122s disease molecules in cell cultures acutely infected with herpes simplex virus type 1","volume":"6","author":"Wozniak","year":"2011","journal-title":"PLoS One"},{"key":"B53","doi-asserted-by":"publisher","first-page":"141","DOI":"10.1177\/1756285610370069","article-title":"Antiviral agents in Alzheimer\u00e2\u20ac\u2122s disease: hope for the future?","volume":"3","author":"Wozniak","year":"2010","journal-title":"Ther. Adv. Neurol. Disord."},{"key":"B54","doi-asserted-by":"publisher","first-page":"7","DOI":"10.1016\/j.jneuroim.2013.01.005","article-title":"Intravenous immunoglobulin reduces \u00ce\u00b2 amyloid and abnormal tau formation caused by herpes simplex virus type 1","volume":"257","author":"Wozniak","year":"2013b","journal-title":"J. Neuroimmunol."},{"key":"B52","doi-asserted-by":"publisher","first-page":"95","DOI":"10.1016\/j.neulet.2007.09.077","article-title":"Herpes simplex virus infection causes cellular beta-amyloid accumulation and secretase upregulation","volume":"429","author":"Wozniak","year":"2007","journal-title":"Neurosci. Lett."},{"key":"B55","doi-asserted-by":"publisher","first-page":"131","DOI":"10.1002\/path.2449","article-title":"Herpes simplex virus type 1 DNA is located within Alzheimer\u00e2\u20ac\u2122s disease amyloid plaques","volume":"217","author":"Wozniak","year":"2009","journal-title":"J. Pathol."},{"key":"B56","doi-asserted-by":"publisher","first-page":"300","DOI":"10.1002\/jmv.20271","article-title":"Productive herpes simplex virus in brain of elderly normal subjects and Alzheimer\u00e2\u20ac\u2122s disease patients","volume":"75","author":"Wozniak","year":"2005","journal-title":"J. Med. Virol."},{"key":"B57","doi-asserted-by":"publisher","first-page":"27","DOI":"10.1186\/1750-1326-5-27","article-title":"First evidence of overlaps between HIV-associated dementia (HAD) and non-viral neurodegenerative diseases: proteomic analysis of the frontal cortex from HIV+ patients with and without dementia","volume":"5","author":"Zhou","year":"2010","journal-title":"Mol. Neurodegener."}],"container-title":["Frontiers in Aging Neuroscience"],"original-title":[],"deposited":{"date-parts":[[2017,6,22]],"date-time":"2017-06-22T14:16:47Z","timestamp":1498141007000},"score":1,"resource":{"primary":{"URL":"http:\/\/journal.frontiersin.org\/article\/10.3389\/fnagi.2014.00202\/abstract"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2014,8,11]]},"references-count":61,"URL":"https:\/\/doi.org\/10.3389\/fnagi.2014.00202","relation":{},"ISSN":["1663-4365"],"issn-type":[{"value":"1663-4365","type":"electronic"}],"subject":[],"published":{"date-parts":[[2014,8,11]]}}}