{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T14:10:16Z","timestamp":1790604616282,"version":"4.1.0"},"reference-count":40,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2022,3,30]],"date-time":"2022-03-30T00:00:00Z","timestamp":1648598400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100005297","name":"Medical University of Bia\u0142ystok","doi-asserted-by":"publisher","award":["SUB\/1\/DN\/21\/001\/1148"],"award-info":[{"award-number":["SUB\/1\/DN\/21\/001\/1148"]}],"id":[{"id":"10.13039\/501100005297","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Viruses"],"abstract":"<jats:p>Alzheimer\u2019s disease (AD) has emerged as a growing threat to human health. It is a multifactorial disorder, in which abnormal amyloid beta metabolism and neuroinflammation have been demonstrated to play a key role. Intrathecal inflammation can be triggered by infections and precede brain damage for years. We analyzed the influence of infections of the central nervous system on biomarkers that are crucially involved in AD pathology. Analyses of the cerebrospinal fluid (CSF) levels of A\u03b21\u201342, A\u03b21\u201340, Tau, and pTau proteins were performed in 53 children with neuroinfections of viral (n = 26) and bacterial origin (n = 19), and in controls (n = 8). We found no changes in CSF amyloid A\u03b21\u201342 concentrations, regardless of etiology. We showed an increase in tau and phosphorylated tau concentrations in purulent CNS infections of the brain, compared to other etiologies. Moreover, the total concentrations of tau in the CSF correlated with the CSF absolute number of neutrophils. These findings and the A\u03b2 42\/40 concentration quotient discrepancies in CFS between meningitis and encephalitis suggest that infections may affect the metabolism of AD biomarkers.<\/jats:p>","DOI":"10.3390\/v14040725","type":"journal-article","created":{"date-parts":[[2022,3,30]],"date-time":"2022-03-30T21:24:42Z","timestamp":1648675482000},"page":"725","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Amyloid and Tau Protein Concentrations in Children with Meningitis and Encephalitis"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8391-4793","authenticated-orcid":false,"given":"Artur","family":"Sulik","sequence":"first","affiliation":[{"name":"Department of Pediatric Infectious Diseases, Medical University of Bialystok, Waszyngtona 17, 15-274 Bialystok, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0309-6987","authenticated-orcid":false,"given":"Kacper","family":"Toczylowski","sequence":"additional","affiliation":[{"name":"Department of Pediatric Infectious Diseases, Medical University of Bialystok, Waszyngtona 17, 15-274 Bialystok, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Agnieszka","family":"Kulczynska-Przybik","sequence":"additional","affiliation":[{"name":"Department of Neurodegeneration Diagnostics, Medical University of Bialystok, Waszyngtona 15A, 15-269 Bialystok, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4075-8479","authenticated-orcid":false,"given":"Barbara","family":"Mroczko","sequence":"additional","affiliation":[{"name":"Department of Neurodegeneration Diagnostics, Medical University of Bialystok, Waszyngtona 15A, 15-269 Bialystok, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,3,30]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"30","DOI":"10.1038\/s41582-019-0281-2","article-title":"Cerebral Amyloid Angiopathy and Alzheimer Disease\u2014One Peptide, Two Pathways","volume":"16","author":"Greenberg","year":"2020","journal-title":"Nat. Rev. Neurol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"733","DOI":"10.1007\/s12640-018-9895-1","article-title":"Clearance of Amyloid Beta and Tau in Alzheimer\u2019s Disease: From Mechanisms to Therapy","volume":"34","author":"Xin","year":"2018","journal-title":"Neurotox. Res."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"921","DOI":"10.1126\/science.8346443","article-title":"Gene Dose of Apolipoprotein E Type 4 Allele and the Risk of Alzheimer\u2019s Disease in Late Onset Families","volume":"261","author":"Corder","year":"1993","journal-title":"Science"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"375","DOI":"10.1016\/j.neuron.2018.09.022","article-title":"The Meningeal Lymphatic System: A New Player in Neurophysiology","volume":"100","author":"Fu","year":"2018","journal-title":"Neuron"},{"key":"ref_5","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_6","doi-asserted-by":"crossref","first-page":"678","DOI":"10.3390\/v5020678","article-title":"Directional Spread of Alphaherpesviruses in the Nervous System","volume":"5","author":"Kramer","year":"2013","journal-title":"Viruses"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"2038","DOI":"10.12688\/f1000research.8886.1","article-title":"Herpes Simplex Virus and the Lexicon of Latency and Reactivation: A Call for Defining Terms and Building an Integrated Collective Framework","volume":"5","author":"Sawtell","year":"2016","journal-title":"F1000Research"},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Wozniak, M.A., Frost, A.L., Preston, C.M., and Itzhaki, R.F. (2011). Antivirals Reduce the Formation of Key Alzheimer\u2019s Disease Molecules in Cell Cultures Acutely Infected with Herpes Simplex Virus Type 1. PLoS ONE, 6.","DOI":"10.1371\/journal.pone.0025152"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"64","DOI":"10.1016\/j.neuron.2018.05.023","article-title":"Multiscale Analysis of Independent Alzheimer\u2019s Cohorts Finds Disruption of Molecular, Genetic, and Clinical Networks by Human Herpesvirus","volume":"99","author":"Readhead","year":"2018","journal-title":"Neuron"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"634","DOI":"10.1007\/s13365-019-00732-3","article-title":"Does HIV Infection Contribute to Increased Beta-Amyloid Synthesis and Plaque Formation Leading to Neurodegeneration and Alzheimer\u2019s Disease?","volume":"25","author":"Fulop","year":"2019","journal-title":"J. Neurovirol."},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Hammond, C.J., Hallock, L.R., Howanski, R.J., Appelt, D.M., Little, C.S., and Balin, B.J. (2010). Immunohistological Detection of Chlamydia Pneumoniae in the Alzheimer\u2019s Disease Brain. BMC Neurosci., 11.","DOI":"10.1186\/1471-2202-11-121"},{"key":"ref_12","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_13","doi-asserted-by":"crossref","first-page":"228","DOI":"10.1016\/j.neurobiolaging.2005.01.018","article-title":"Beta-Amyloid Deposition and Alzheimer\u2019s Type Changes Induced by Borrelia Spirochetes","volume":"27","author":"Miklossy","year":"2006","journal-title":"Neurobiol. Aging"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"280","DOI":"10.1016\/j.jalz.2011.03.003","article-title":"Toward Defining the Preclinical Stages of Alzheimer\u2019s Disease: Recommendations from the National Institute on Aging-Alzheimer\u2019s Association Workgroups on Diagnostic Guidelines for Alzheimer\u2019s Disease","volume":"7","author":"Sperling","year":"2011","journal-title":"Alzheimer\u2019s Dement."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1080\/14712598.2019.1554646","article-title":"A Vaccine against Alzheimer\u2019s Disease: Anything Left but Faith?","volume":"19","author":"Bachmann","year":"2019","journal-title":"Expert Opin. Biol. Ther."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.ejim.2019.01.004","article-title":"Tick-Borne Encephalitis in Europe: A Brief Update on Epidemiology, Diagnosis, Prevention, and Treatment","volume":"62","author":"Riccardi","year":"2019","journal-title":"Eur. J. Intern. Med."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"76","DOI":"10.32394\/pe.75.08","article-title":"Epidemiology of Tick-Borne Encephalitis in Poland (2010\u20132019) and the Impact of the COVID-19 Pandemic on the Notified Incidence of the Disease","volume":"75","author":"Sulik","year":"2021","journal-title":"Prz. Epidemiol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"210","DOI":"10.32394\/pe.75.19","article-title":"Lyme Disease in Poland in 2019","volume":"75","author":"Rosolak","year":"2021","journal-title":"Prz. Epidemiol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"455","DOI":"10.2217\/bmm.12.42","article-title":"Upcoming Candidate Cerebrospinal Fluid Biomarkers of Alzheimer\u2019s Disease","volume":"6","author":"Fagan","year":"2012","journal-title":"Biomark. Med."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1205","DOI":"10.1038\/aps.2017.28","article-title":"Amyloid Beta: Structure, Biology and Structure-Based Therapeutic Development","volume":"38","author":"Chen","year":"2017","journal-title":"Acta Pharmacol. Sin."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"640","DOI":"10.1016\/j.bcp.2013.12.024","article-title":"Alzheimer Disease: Epidemiology, Diagnostic Criteria, Risk Factors and Biomarkers","volume":"88","author":"Reitz","year":"2014","journal-title":"Biochem. Pharmacol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"620","DOI":"10.1007\/s00415-012-6688-y","article-title":"Cerebrospinal Fluid Alzheimer\u2019s Biomarker Profiles in CNS Infections","volume":"260","author":"Krut","year":"2013","journal-title":"J. Neurol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1490","DOI":"10.1212\/01.wnl.0000183293.95787.b7","article-title":"CSF Amyloid Beta42 and Tau Levels Correlate with AIDS Dementia Complex","volume":"65","author":"Brew","year":"2005","journal-title":"Neurology"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"152","DOI":"10.3389\/fnagi.2018.00152","article-title":"A Specific Reduction in A\u03b21-42 vs. a Universal Loss of A\u03b2 Peptides in CSF Differentiates Alzheimer\u2019s Disease From Meningitis and Multiple Sclerosis","volume":"10","author":"Spitzer","year":"2018","journal-title":"Front. Aging Neurosci."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1443","DOI":"10.1007\/s10096-019-03569-0","article-title":"Enteroviral Meningitis Reduces CSF Concentration of A\u03b242, but Does Not Affect Markers of Parenchymal Damage","volume":"38","author":"Toczylowski","year":"2019","journal-title":"Eur. J. Clin. Microbiol. Infect. Dis."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1016\/S0304-3940(01)02285-6","article-title":"Low Cerebrospinal Fluid Beta-Amyloid 42 in Patients with Acute Bacterial Meningitis and Normalization after Treatment","volume":"314","author":"Vanmechelen","year":"2001","journal-title":"Neurosci. Lett."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"402","DOI":"10.1017\/S1092852919000981","article-title":"Cerebrospinal Fluid Biomarkers in Patients with Central Nervous System Infections: A Retrospective Study","volume":"25","author":"Alcantarini","year":"2020","journal-title":"CNS Spectr."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"169028","DOI":"10.1100\/2012\/169028","article-title":"Tuberculous Meningitis in Adults: A Review of 160 Cases","volume":"2012","author":"Pehlivanoglu","year":"2012","journal-title":"Sci. World J."},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Mattsson, N., Bremell, D., Anckars\u00e4ter, R., Blennow, K., Anckars\u00e4ter, H., Zetterberg, H., and Hagberg, L. (2010). Neuroinflammation in Lyme Neuroborreliosis Affects Amyloid Metabolism. BMC Neurol., 10.","DOI":"10.1186\/1471-2377-10-51"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"34","DOI":"10.1186\/s13195-019-0485-0","article-title":"Advantages and Disadvantages of the Use of the CSF Amyloid \u03b2 (A\u03b2) 42\/40 Ratio in the Diagnosis of Alzheimer\u2019s Disease","volume":"11","author":"Hansson","year":"2019","journal-title":"Alzheimer\u2019s Res. Ther."},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Lewczuk, P., Wiltfang, J., Kornhuber, J., and Verhasselt, A. (2021). Distributions of A\u03b242 and A\u03b242\/40 in the Cerebrospinal Fluid in View of the Probability Theory. Diagnostics, 11.","DOI":"10.3390\/diagnostics11122372"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"813","DOI":"10.3233\/JAD-160722","article-title":"Cerebrospinal Fluid A\u03b242\/40 Corresponds Better than A\u03b242 to Amyloid PET in Alzheimer\u2019s Disease","volume":"55","author":"Lewczuk","year":"2017","journal-title":"J. Alzheimer\u2019s Dis."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1186\/s13195-020-00696-1","article-title":"Cerebrospinal Fluid A Beta 1\u201340 Peptides Increase in Alzheimer\u2019s Disease and Are Highly Correlated with Phospho-Tau in Control Individuals","volume":"12","author":"Lehmann","year":"2020","journal-title":"Alzheimer\u2019s Res. Ther."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"30","DOI":"10.1016\/j.exger.2009.10.010","article-title":"Total and Phosphorylated Tau Protein as Biological Markers of Alzheimer\u2019s Disease","volume":"45","author":"Hampel","year":"2010","journal-title":"Exp. Gerontol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1183","DOI":"10.1038\/s41593-020-0687-6","article-title":"Synergy between Amyloid-\u03b2 and Tau in Alzheimer\u2019s Disease","volume":"23","author":"Busche","year":"2020","journal-title":"Nat. Neurosci."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"570045","DOI":"10.3389\/fnmol.2020.570045","article-title":"Tau Protein and Its Role in Blood\u2013Brain Barrier Dysfunction","volume":"13","author":"Michalicova","year":"2020","journal-title":"Front. Mol. Neurosci."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"479","DOI":"10.1007\/s10096-018-03447-1","article-title":"Assessment of the Tau Protein Concentration in Patients with Tick-Borne Encephalitis","volume":"38","author":"Czupryna","year":"2019","journal-title":"Eur. J. Clin. Microbiol. Infect. Dis."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"316","DOI":"10.32394\/pe.74.24","article-title":"Tick-Borne Encephalitis-a Review of Current Epidemiology, Clinical Symptoms, Management and Prevention","volume":"74","author":"Bojkiewicz","year":"2020","journal-title":"Prz. Epidemiol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"240","DOI":"10.1186\/s12974-018-1284-4","article-title":"The Role of Neutrophil Granule Proteins in Neuroinflammation and Alzheimer\u2019s Disease","volume":"15","author":"Stock","year":"2018","journal-title":"J. Neuroinflammation"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"880","DOI":"10.1038\/nm.3913","article-title":"Neutrophils Promote Alzheimer\u2019s Disease-like Pathology and Cognitive Decline via LFA-1 Integrin","volume":"21","author":"Zenaro","year":"2015","journal-title":"Nat. Med."}],"container-title":["Viruses"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1999-4915\/14\/4\/725\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T22:46:59Z","timestamp":1760136419000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1999-4915\/14\/4\/725"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,3,30]]},"references-count":40,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2022,4]]}},"alternative-id":["v14040725"],"URL":"https:\/\/doi.org\/10.3390\/v14040725","relation":{},"ISSN":["1999-4915"],"issn-type":[{"value":"1999-4915","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,3,30]]}}}