{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T01:34:15Z","timestamp":1760060055398,"version":"build-2065373602"},"reference-count":107,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2025,7,27]],"date-time":"2025-07-27T00:00:00Z","timestamp":1753574400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biomolecules"],"abstract":"<jats:p>Alzheimer\u2019s Disease (AD) is a multifactorial process. Amyloid plaque formation constitutes the main characteristic of the disease. Despite the identification of numerous factors associated with AD, the mechanism remains unclear in several aspects. Disturbances in intestinal and blood\u2013brain barrier (BBB) penetration, observed in AD, may facilitate immunologic response to food-derived antigens. In the present study, antibodies against egg albumin, bovine-casein, and N-Glycolyl-Neuraminic acid (Neu5Gc) were measured in the cerebrospinal fluid (CSF) and serum of the patients using an enzyme-linked immunosorbent assay (ELISA). Zero anti-Neu5Gc and low concentrations of anti-casein antibodies were detected. Increased anti-native egg albumin antibodies were present in the serum of patients of all stages with 65% positivity (p &lt; 0.001) in mild disease and a higher percentage in females (81.9%, p &lt; 0.001). Lower serum positivity to anti-denatured egg albumin antibodies was observed, showing a gradual increase with severity and higher prevalence also in females. In the CSF, anti-native and anti-denatured egg albumin antibodies were mainly observed in severely ill patients with accumulative positivity to either antigen, reaching 61.8% in severe vs. 15% in mild disease (p &lt; 0.001). Increased values were mainly observed in males. Anti-egg albumin antibodies may be implicated in the disease mechanism through sequence\/structural similarity with human proteins, mainly serpins, and it would be worth consideration in further investigations and therapeutic strategies.<\/jats:p>","DOI":"10.3390\/biom15081085","type":"journal-article","created":{"date-parts":[[2025,7,28]],"date-time":"2025-07-28T07:57:24Z","timestamp":1753689444000},"page":"1085","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Increased Concentration of Anti-Egg Albumin Antibodies in Cerebrospinal Fluid and Serum of Patients with Alzheimer\u2019s Disease\u2014Discussion on Human Serpins\u2019 Similarity and Probable Involvement in the Disease Mechanism"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5849-4192","authenticated-orcid":false,"given":"Dionysia","family":"Amanatidou","sequence":"first","affiliation":[{"name":"School of Health, Department of Biomedical Sciences, International Hellenic University, Sindos, 57400 Thessaloniki, Greece"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2072-8010","authenticated-orcid":false,"given":"Magdalini","family":"Tsolaki","sequence":"additional","affiliation":[{"name":"Laboratory of Neurodegenerative Diseases, Center for Interdisciplinary Research and Innovation (CIRI-AUTh), Balkan Center, Aristotle University of Thessaloniki, Building A, 57001 Thessaloniki, Greece"},{"name":"Alzheimer Hellas, 13 Petrou Sindika st., 54643 Thessaloniki, Greece"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Vasileios","family":"Fouskas","sequence":"additional","affiliation":[{"name":"School of Health, Department of Biomedical Sciences, International Hellenic University, Sindos, 57400 Thessaloniki, Greece"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ioannis","family":"Gavriilidis","sequence":"additional","affiliation":[{"name":"School of Health, Department of Biomedical Sciences, International Hellenic University, Sindos, 57400 Thessaloniki, Greece"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maria","family":"Myriouni","sequence":"additional","affiliation":[{"name":"School of Health, Department of Biomedical Sciences, International Hellenic University, Sindos, 57400 Thessaloniki, Greece"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anna","family":"Anastasiou","sequence":"additional","affiliation":[{"name":"Laboratory of Neurodegenerative Diseases, Center for Interdisciplinary Research and Innovation (CIRI-AUTh), Balkan Center, Aristotle University of Thessaloniki, Building A, 57001 Thessaloniki, Greece"},{"name":"Alzheimer Hellas, 13 Petrou Sindika st., 54643 Thessaloniki, Greece"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Efthimia","family":"Papageorgiou","sequence":"additional","affiliation":[{"name":"Laboratory of Neurodegenerative Diseases, Center for Interdisciplinary Research and Innovation (CIRI-AUTh), Balkan Center, Aristotle University of Thessaloniki, Building A, 57001 Thessaloniki, Greece"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Diona","family":"Porfyriadou","sequence":"additional","affiliation":[{"name":"School of Health, Department of Biomedical Sciences, International Hellenic University, Sindos, 57400 Thessaloniki, Greece"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-0150-8993","authenticated-orcid":false,"given":"Zoi","family":"Parcharidi","sequence":"additional","affiliation":[{"name":"School of Health, Department of Biomedical Sciences, International Hellenic University, Sindos, 57400 Thessaloniki, Greece"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eleftheria","family":"Papasavva","sequence":"additional","affiliation":[{"name":"School of Health, Department of Biomedical Sciences, International Hellenic University, Sindos, 57400 Thessaloniki, Greece"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maria","family":"Fili","sequence":"additional","affiliation":[{"name":"School of Health, Department of Biomedical Sciences, International Hellenic University, Sindos, 57400 Thessaloniki, Greece"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8376-752X","authenticated-orcid":false,"given":"Phaedra","family":"Eleftheriou","sequence":"additional","affiliation":[{"name":"School of Health, Department of Biomedical Sciences, International Hellenic University, Sindos, 57400 Thessaloniki, Greece"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,7,27]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"19","DOI":"10.4318\/tjg.2012.0332","article-title":"The effects of provocation by foods with raised IgG antibodies and additives on the course of Crohn\u2019s disease: A pilot study","volume":"23","author":"Uzunismail","year":"2012","journal-title":"Turk. J. Gastroenterol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1186\/s12986-020-00528-x","article-title":"Food-specific serum IgG and symptom reduction with a personalized, unrestricted-calorie diet of six weeks in Irritable Bowel Syndrome (IBS)","volume":"17","author":"Cappelletti","year":"2020","journal-title":"Nutr. Metab."},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Eleftheriou, P., Kynigopoulos, S., Giovou, A., Mazmanidi, A., Yovos, J., Skepastianos, P., Vagdatli, E., Petrou, C., Papara, D., and Efterpiou, M. (2014). Prevalence of anti-Neu5Gc antibodies in patients with hypothyroidism. Biomed. Res. Int., 2014.","DOI":"10.1155\/2014\/963230"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"3352","DOI":"10.1158\/0008-5472.CAN-10-4102","article-title":"Human xeno-autoantibodies against a non-human sialic acid serve as novel serum biomarkers and immunotherapeutics in cancer","volume":"71","author":"Pu","year":"2011","journal-title":"Cancer Res."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"79","DOI":"10.1007\/s11916-019-0819-4","article-title":"The clinical use of IgG food sensitivity testing with migraine headache patients: A literature review","volume":"23","author":"Geiselman","year":"2019","journal-title":"Curr. Pain Headache Rep."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"e2117034119","DOI":"10.1073\/pnas.2117034119","article-title":"Antibody cross-reactivity between casein and myelin-associated glycoprotein results in central nervous system demyelination","volume":"119","author":"Chundera","year":"2022","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"318","DOI":"10.1016\/S1474-4422(09)70290-X","article-title":"Gluten sensitivity: From gut to brain","volume":"9","author":"Hadjivassiliou","year":"2010","journal-title":"Lancet Neurol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"653","DOI":"10.1016\/S1474-4422(10)70148-4","article-title":"Gluten sensitivity and the CNS: Diagnosis and treatment","volume":"9","author":"Versino","year":"2010","journal-title":"Lancet Neurol."},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Karakula-Juchnowicz, H., Galecka, M., Rog, J., Bartnicka, A., Lukaszewicz, Z., Krukow, P., Morylowska-Topolska, J., Skonieczna-Zydecka, K., Krajka, T., and Jonak, K. (2018). The food-specific serum IgG reactivity in major depressive disorder patients, irritable bowel syndrome patients and healthy controls. Nutrients, 10.","DOI":"10.3390\/nu10050548"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"834","DOI":"10.1111\/j.1399-5618.2010.00879.x","article-title":"Immune activation by casein dietary antigens in bipolar disorder","volume":"12","author":"Severance","year":"2010","journal-title":"Bipolar Disord."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"110","DOI":"10.1179\/1476830514Y.0000000158","article-title":"The role of IgG hypersensitivity in the pathogenesis and therapy of depressive disorders","volume":"20","author":"Szachta","year":"2017","journal-title":"Nutr. Neurosci."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1800","DOI":"10.1111\/ijfs.14467","article-title":"Reaction of food-specific antibodies with different tissue antigens","volume":"55","author":"Vojdani","year":"2020","journal-title":"Int. J. Food Sci. Technol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"244","DOI":"10.1038\/nri1784","article-title":"Aberrant homing of mucosal T cells and extra-intestinal manifestations of inflammatory bowel disease","volume":"6","author":"Adams","year":"2006","journal-title":"Nat. Rev. Immunol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"188","DOI":"10.1016\/j.it.2006.02.006","article-title":"A gut feeling for joint inflammation\u2014Using coeliac disease to understand rheumatoid arthritis","volume":"27","author":"Molberg","year":"2006","journal-title":"Trends Immunol."},{"key":"ref_15","first-page":"437231","article-title":"A potential link between environmental triggers and autoimmunity","volume":"2024","author":"Vojdani","year":"2014","journal-title":"Autoimmune Dis."},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"De Magistris, L., Picardi, A., Siniscalco, D., Riccio, M.P., Sapone, A., Cariello, R., Abbadessa, S., Medici, N., Lammers, K.M., and Schiraldi, C. (2013). Antibodies against Food Antigens in Patients with Autistic Spectrum Disorders. BioMed Res. Int., 2013.","DOI":"10.1155\/2013\/729349"},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Rowland, L.M., Demyanovich, H.K., Wijtenburg, S.A., Eaton, W.W., Rodriguez, K., Gaston, F., Cihakova, D., Talor, M.V., Liu, F., and McMahon, R.R. (2017). Antigliadin Antibodies (AgA IgG) Are Related to Neurochemistry in Schizophrenia. Front. Psychiatry, 8.","DOI":"10.3389\/fpsyt.2017.00104"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"252","DOI":"10.1159\/000264649","article-title":"Clinical relevance of IgG antibodies against food antigens in Crohn\u2019s disease: A double-blind cross-over diet intervention study","volume":"81","author":"Bentz","year":"2010","journal-title":"Digestion"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1459","DOI":"10.1136\/gut.2003.037697","article-title":"Food elimination based on IgG anti-bodies in irritable bowel syndrome: A randomised controlled trial","volume":"53","author":"Atkinson","year":"2004","journal-title":"Gut"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"85","DOI":"10.1186\/1475-2891-10-85","article-title":"Randomised con-trolled trial of food elimination diet based on IgG antibodies for the prevention of migraine like headaches","volume":"10","author":"Mitchell","year":"2011","journal-title":"Nutr. J."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"7890461","DOI":"10.1155\/2019\/7890461","article-title":"Effects of diet based on IgG elimination combined with probiotics on migraine plus irritable bowel syndrome","volume":"2019","author":"Xie","year":"2019","journal-title":"Pain Res. Manag."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1918","DOI":"10.1093\/ibd\/izy110","article-title":"Food exclusion based on IgG antibodies alleviates symptoms in ulcerative colitis: A prospective study","volume":"24","author":"Jian","year":"2018","journal-title":"Inflamm. Bowel Dis."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1148","DOI":"10.1007\/s10620-015-3987-z","article-title":"Treatment of Crohn\u2019s disease with an IgG4-guided exclusion diet: A randomized controlled trial","volume":"61","author":"Gunasekeera","year":"2016","journal-title":"Dig. Dis. Sci."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"101451","DOI":"10.1016\/j.arr.2021.101451","article-title":"Abnormal amyloid beta metabolism in systemic abnormalities and Alzheimer\u2019s pathology: Insights and therapeutic approaches from periphery","volume":"71","author":"Ullah","year":"2021","journal-title":"Ageing Res. Rev."},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"De Bruijn, R.F.A.G., and Ikram, M.A. (2014). Cardiovascular risk factors and future risk of Alzheimer\u2019s disease. BMC Med., 12.","DOI":"10.1186\/s12916-014-0130-5"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"64","DOI":"10.1016\/S1474-4422(05)70284-2","article-title":"Risk of dementia in diabetes mellitus: A systematic review","volume":"5","author":"Biessels","year":"2006","journal-title":"Lancet Neurol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"219683","DOI":"10.1155\/2010\/219683","article-title":"Diet and age interactions with regards to cholesterol regulation and brain pathogenesis","volume":"2010","author":"Uranga","year":"2010","journal-title":"Curr. Gerontol. Geriatr. Res."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"424","DOI":"10.1016\/S2215-0366(18)30065-8","article-title":"Long-term risk of dementia among people with traumatic brain injury in Denmark: A population-based observational cohort study","volume":"5","author":"Fann","year":"2018","journal-title":"Lancet Psychiatry"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"718","DOI":"10.1016\/S0140-6736(16)32399-6","article-title":"Living near major roads and the incidence of dementia, Parkinson\u2019s disease, and multiple sclerosis: A population-based cohort study","volume":"389","author":"Chen","year":"2017","journal-title":"Lancet"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1693","DOI":"10.1016\/j.bbadis.2014.06.010","article-title":"Elevated risk of type 2 diabetes for development of Alzheimer disease: A key role for oxidative stress in brain","volume":"1842","author":"Butterfield","year":"2014","journal-title":"Biochim. Et Biophys. Acta (BBA) Mol. Basis Dis."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"668","DOI":"10.1001\/archneur.61.5.668","article-title":"Inflammatory proteins in plasma and the risk of dementia","volume":"61","author":"Engelhart","year":"2004","journal-title":"Arch. Neurol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"957","DOI":"10.1001\/jama.2019.1432","article-title":"Association of midlife diet with subsequent risk for dementia","volume":"321","author":"Akbaraly","year":"2019","journal-title":"J. Am. Med. Assoc."},{"key":"ref_33","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_34","doi-asserted-by":"crossref","first-page":"435","DOI":"10.1186\/s13071-021-04928-7","article-title":"Risk of dementia in patients with toxoplasmosis: A nationwide, population based cohort study in Taiwan","volume":"14","author":"Yang","year":"2021","journal-title":"Parasites Vectors"},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Wu, S., Liu, X., Jiang, R., Yan, X., and Ling, Z. (2021). Roles and Mechanisms of Gut Microbiota in Patients With Alzheimer\u2019s Disease. Front. Aging Neurosci., 13.","DOI":"10.3389\/fnagi.2021.650047"},{"key":"ref_36","first-page":"481","article-title":"Studies on the specificity of antibodies to ovalbumin in normal human serum: Technical considerations in the use of ELISA methods","volume":"66","author":"Kilshaw","year":"1986","journal-title":"Clin. Exp. Immunol."},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"Yang, W., Jiang, Y., Guo, Q., Tian, Z., and Cheng, Z. (2022). Aberrant N-glycolylneuraminic acid in breast MCF-7 cancer cells and cancer stem cells. Front. Mol. Biosci., 9.","DOI":"10.3389\/fmolb.2022.1047672"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1635","DOI":"10.1271\/bbb.66.1635","article-title":"Heating of an Ovalbumin Solution at Neutral pH and High Temperature","volume":"66","author":"Photchanachai","year":"2002","journal-title":"Biosci. Biotechnol. Biochem."},{"key":"ref_39","unstructured":"Conover, W.J. (1999). Practical Nonparametric Statistics, John Wiley & Sons. [3rd ed.]."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"591","DOI":"10.1093\/biomet\/52.3-4.591","article-title":"An analysis of variance test for normality","volume":"52","author":"Shapiro","year":"1999","journal-title":"Biometrika"},{"key":"ref_41","unstructured":"Lentner, C.G. (1982). Scientific Tablesed, Ciba-Geigy. [8th ed.]."},{"key":"ref_42","unstructured":"Rosner, B. (2006). Fundamentals of Biostatistics, Tomson Brooks\/Cole. [6th ed.]."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"152","DOI":"10.5395\/rde.2017.42.2.152","article-title":"Statistical notes for clinical researchers: Chi-squared test and Fisher\u2019s exact test","volume":"42","author":"Kim","year":"2017","journal-title":"Restor. Dent. Endod."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"100032","DOI":"10.1016\/j.bbih.2019.100032","article-title":"The origin and nature of the complex autoantibody profile in cerebrospinal fluid","volume":"2","author":"Kheirkhah","year":"2020","journal-title":"Brain Behav. Immun. Health"},{"key":"ref_45","doi-asserted-by":"crossref","unstructured":"Aiello, A., Farzaneh, F., Candore, G., Caruso, C., Davinelli, S., Gambino, C.M., Ligotti, M.E., Zareian, N., and Accardi, G. (2019). Immunosenescence and Its Hallmarks: How to Oppose Aging Strategically? A Review of Potential Options for Therapeutic Intervention. Front. Immunol., 10.","DOI":"10.3389\/fimmu.2019.02247"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"2206504","DOI":"10.1080\/19490976.2023.2206504","article-title":"Interlink between the gut microbiota and inflammation in the context of oxidative stress in Alzheimer\u2019s disease progression","volume":"15","author":"Tushar","year":"2023","journal-title":"Gut Microbes"},{"key":"ref_47","doi-asserted-by":"crossref","unstructured":"Honarpisheh, P., Reynolds, C.R., Blasco Conesa, M.P., Moruno Manchon, J.F., Putluri, N., Bhattacharjee, M.B., Urayama, A., McCullough, L.D., and Ganesh, B.P. (2020). Ganesh Dysregulated Gut Homeostasis Observed Prior to the Accumulation of the Brain Amyloid in Tg2576 Mice. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21051711"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"213","DOI":"10.1016\/j.bbrc.2004.05.154","article-title":"Albumin-bound polyacrolein: Implications for Alzheimer\u2019s disease","volume":"320","author":"Seidler","year":"2004","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"30804","DOI":"10.1074\/jbc.M804048200","article-title":"The Structural Basis of Serpin Polymerization Studied by Hydrogen\/Deuterium Exchange and Mass Spectrometry","volume":"283","author":"Tsutsui","year":"2008","journal-title":"J. Biol. Chem."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"1158","DOI":"10.1016\/j.foodchem.2016.11.043","article-title":"Prediction of heat-induced polymerization of different globular food proteins in mixtures with wheat gluten","volume":"221","author":"Lambrecht","year":"2017","journal-title":"Food Chem."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"23518","DOI":"10.1074\/jbc.M113.470450","article-title":"Formation of Dynamic Soluble Surfactant-induced Amyloid Peptide Aggregation Intermediates","volume":"288","author":"Abelein","year":"2013","journal-title":"J. Biol. Chem."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"333","DOI":"10.1016\/j.clim.2007.03.001","article-title":"Serum surfactant protein D is correlated to development of dementia and augmented mortality","volume":"123","author":"Nybo","year":"2007","journal-title":"Clin. Immunol."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"20969","DOI":"10.1039\/C7RA01934C","article-title":"Monitoring surfactant mediated defence of gastrointestinal Proteus mirabilis DMTMMK1against pathogenic consortia of Vibrio cholerae","volume":"7","author":"Kannan","year":"2017","journal-title":"RSC Adv."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"111759","DOI":"10.1016\/j.jfoodeng.2023.111759","article-title":"Regulating the thermal properties of egg white by adding surfactants","volume":"362","author":"Jiang","year":"2024","journal-title":"J. Food Eng."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"26489","DOI":"10.1074\/jbc.R113.462929","article-title":"Oxidant Sensing by Reversible Disulfide Bond","volume":"288","author":"Cremers","year":"2013","journal-title":"J. Biol. Chem."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"1512","DOI":"10.1136\/gut.2005.085373","article-title":"Recent advances in clinical practice. Alterations in intestinal permeability","volume":"55","author":"Arrieta","year":"2006","journal-title":"Gut"},{"key":"ref_57","doi-asserted-by":"crossref","unstructured":"Heston, M.B., Hanslik, K.L., Zarbock, K.R., Harding, S.J., Davenport-Sis, N.J., Kerby, R.L., Chin, N., Sun, Y., Hoeft, A., and Deming, Y. (2023). Gut inflammation associated with age and Alzheimer\u2019s disease pathology: A human cohort study. Sci. Rep., 13.","DOI":"10.1038\/s41598-023-45929-z"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"180","DOI":"10.1002\/ame2.12033","article-title":"The intestinal microbiome and Alzheimer\u2019s disease: A review","volume":"1","author":"Li","year":"2018","journal-title":"Animal Models. Exp. Med."},{"key":"ref_59","doi-asserted-by":"crossref","unstructured":"Pellegrini, C., Daniele, S., Antonioli, L., Benvenuti, L., D\u2019Antongiovanni, V., Piccarducci, R., Pietrobono, D., Citi, V., Piragine, E., and Flori, L. (2020). Prodromal Intestinal Events in Alzheimer\u2019s Disease (AD): Colonic Dysmotility and Inflammation Are Associated with Enteric AD-Related Protein Deposition. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21103523"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"314","DOI":"10.5056\/jnm20208","article-title":"Roles of Sex Hormones and Gender in the Gut Microbiota","volume":"27","author":"Yoon","year":"2021","journal-title":"J. Neurogastroenterol. Motil."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"48","DOI":"10.5534\/wjmh.190009","article-title":"Sex Differences in Gut Microbiota","volume":"38","author":"Kim","year":"2020","journal-title":"World J. Men\u2019s Health"},{"key":"ref_62","doi-asserted-by":"crossref","unstructured":"Towera, J., Pomattod, L.C.D., and Daviesa, K.J.A. (2020). Sex differences in the response to oxidative and proteolytic stress. Redox Biol., 31.","DOI":"10.1016\/j.redox.2020.101488"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"1024","DOI":"10.1111\/jcmm.13038","article-title":"Gender difference in oxidative stress: A new look at the mechanisms for cardiovascular diseases","volume":"21","author":"Kander","year":"2017","journal-title":"J. Cell. Mol. Med."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"111802","DOI":"10.1016\/j.mad.2023.111802","article-title":"Sex differences in antioxidant defence and the regulation of redox homeostasis in physiology and pathology","volume":"211","author":"Tiberi","year":"2023","journal-title":"Mech. Ageing Dev."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"14","DOI":"10.1186\/s12987-020-0173-2","article-title":"Increased age and male sex are independently associated with higher frequency of blood\u2013cerebrospinal fluid barrier dysfunction using the albumin quotient","volume":"17","author":"Castellazzi","year":"2020","journal-title":"Fluids Barriers CNS"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"151","DOI":"10.1080\/10284150400004155","article-title":"Immune response to dietary proteins, gliadin and cerebellar peptides in children with autism","volume":"7","author":"Vojdani","year":"2004","journal-title":"Nutr. Neurosci."},{"key":"ref_67","doi-asserted-by":"crossref","unstructured":"Cie\u2019 sli\u2019 nska, A., Fiedorowicz, E., Rozmus, D., Sienkiewicz-Sz\u0142apka, E., Jarmo\u0142owska, B., and Kami\u2019 nski, S. (2022). Does a Little Difference Make a Big Difference? Bovine-Casein A1 and A2Variants and Human Health\u2014An Update. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms232415637"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"346","DOI":"10.11002\/fsp.2024.31.3.346","article-title":"Ovalbumin: A potential functional protein","volume":"31","author":"Maggonage","year":"2024","journal-title":"Food Sci. Preserv."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"3778","DOI":"10.1007\/s12035-022-02817-3","article-title":"Serpin Signatures in Prion and Alzheimer\u2019s Diseases","volume":"59","author":"Zattoni","year":"2022","journal-title":"Mol. Neurobiol."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"9032","DOI":"10.1523\/JNEUROSCI.2088-07.2007","article-title":"Angiotensin II Controls Occludin Function and Is Required for Blood\u2013Brain Barrier Maintenance: Relevance to Multiple Sclerosis","volume":"27","author":"Wosik","year":"2007","journal-title":"J. Neurosci."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"169649","DOI":"10.1155\/2012\/169649","article-title":"Roles of Brain Angiotensin II in Cognitive Function and Dementia","volume":"2012","author":"Mogi","year":"2012","journal-title":"Int. J. Hypertens."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"1237","DOI":"10.1007\/s11357-020-00231-y","article-title":"Brain angiotensin II and angiotensin IV receptors as potential Alzheimer\u2019s disease therapeutic targets","volume":"42","author":"Royea","year":"2020","journal-title":"GeroScience"},{"key":"ref_73","doi-asserted-by":"crossref","unstructured":"Gebre, A.K., Altaye, B.M., Atey, T.M., Tuem, K.B., and Berhe, D.F. (2018). Targeting Renin\u2013Angiotensin System Against Alzheimer\u2019s Disease. Front. Pharmacol., 9.","DOI":"10.3389\/fphar.2018.00440"},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"276","DOI":"10.1038\/s41590-018-0303-z","article-title":"8SERPINB1-mediated checkpoint of inflammatory caspase activation","volume":"20","author":"Choi","year":"2019","journal-title":"Nat. Immunol."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"478","DOI":"10.1038\/nri3690","article-title":"Mast cell secretory granules: Armed for battle","volume":"14","author":"Wernersson","year":"2014","journal-title":"Nat. Rev. Immunol."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1097\/MOH.0b013e32834115d1","article-title":"Neutrophil serine proteases: Mediators of innate immune responses","volume":"18","author":"Wiedow","year":"2011","journal-title":"Curr. Opin. Hematol."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"1409","DOI":"10.1002\/ibd.21454","article-title":"Intracolonic infusion of fecal supernatants from ulcerative colitis patients triggers altered permeability and inflammation in mice: Role of cathepsin G and protease-activated receptor-4","volume":"17","author":"Dabek","year":"2011","journal-title":"Inflamm. Bowel Dis."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"321","DOI":"10.1016\/S0171-9335(98)80065-4","article-title":"The rat mucosal mast cell chymase RMCP-II alters epithelial cell monolayer permeability in association with altered distribution of the tight junction proteins ZO-1 and occludin","volume":"75","author":"Scudamore","year":"1998","journal-title":"Eur. J. Cell Biol."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"30311","DOI":"10.1074\/jbc.271.48.30311","article-title":"Heat-induced Conversion of Ovalbumin into a Proteinase Inhibitor","volume":"271","author":"Mellet","year":"1996","journal-title":"J. Biol. Chem."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"1150","DOI":"10.1172\/JCI115934","article-title":"The Serpin-Enzyme Complex (SEC) Receptor Mediates the Neutrophil Chemotactic Effect of a-1 Antitrypsin-Elastase Complexes and Amyloid-beta Peptide","volume":"90","author":"Joslin","year":"1992","journal-title":"J. Clin. Investig."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"116","DOI":"10.1016\/j.pnpbp.2012.02.010","article-title":"Decreased serum angiogenin level in Alzheimer\u2019s disease","volume":"38","author":"Kim","year":"2012","journal-title":"Prog. Neuropsychopharmacol. Biol. Psychiatry"},{"key":"ref_82","doi-asserted-by":"crossref","unstructured":"Makuch-Martins, M., Vieira-Morais, C.G., Perego, S.M., Ruggeri, A., Ceroni, A., and Michelini, L.C. (2024). Angiotensin II, blood\u2013brain barrier permeability, and microglia interplay during the transition from pre-to hypertensive phase in spontaneously hypertensive rats. Front. Physiol., 15.","DOI":"10.3389\/fphys.2024.1452959"},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"6409","DOI":"10.1007\/s00018-021-03907-6","article-title":"Neuroserpin: Structure, function, physiology and pathology","volume":"78","author":"Fra","year":"2021","journal-title":"Cell. Mol. Life Sci."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"278","DOI":"10.2174\/187152708784936626","article-title":"Beta-secretase: Structure, Function, and Evolution","volume":"7","author":"Venugopal","year":"2008","journal-title":"CNS Neurol. Disord. Drug Targets"},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"a006379","DOI":"10.1101\/cshperspect.a006379","article-title":"Proteolytic Degradation of Amyloid b-Protein","volume":"2","author":"Saido","year":"2012","journal-title":"Cold Spring Harb. Perspect. Med."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"487","DOI":"10.1016\/0092-8674(88)90462-X","article-title":"Immunochemical identification of the serine protease inhibitor alpha 1-antichymotrypsin in the brain amyloid deposits of Alzheimer\u2019s disease","volume":"52","author":"Abraham","year":"1988","journal-title":"Cell"},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"1341","DOI":"10.1038\/s41593-018-0238-6","article-title":"Propagation and spread of pathogenic protein assemblies in neurodegenerative diseases","volume":"21","author":"Jucker","year":"2018","journal-title":"Nat. Neurosci."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"869","DOI":"10.1016\/S0002-9440(10)65186-3","article-title":"A Role for apoE in Regulating the Levels of a-1-Antichymotrypsin in the Aging Mouse Brain and in Alzheimer\u2019s Disease","volume":"155","author":"Licastro","year":"1999","journal-title":"Am. J. Pathol."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"10967","DOI":"10.1073\/pnas.1434398100","article-title":"Carboxyl-terminal-truncated apolipoprotein E4 causes Alzheimer\u2019s disease-like neurodegeneration and behavioral deficits in transgenic mice","volume":"100","author":"Harris","year":"2003","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"495","DOI":"10.1016\/0197-4580(91)90079-Y","article-title":"Developmental expression of alpha 1-antichymotrypsin in brain may be related to astrogliosis","volume":"12","author":"Koo","year":"1991","journal-title":"Neurobiol. Aging"},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1042\/BJ20061170","article-title":"Identification of a novel targeting sequence for regulated secretion in the serine protease inhibitor neuroserpin","volume":"402","author":"Ishigami","year":"2007","journal-title":"Biochem. J."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"376","DOI":"10.1038\/43894","article-title":"Familial dementia caused by polymerization of mutant neuroserpin","volume":"401","author":"Davis","year":"1999","journal-title":"Nature"},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"29268","DOI":"10.1074\/jbc.M600690200","article-title":"Neuroserpin binds A\u03b2 and is a neuroprotective component of amyloid plaques in Alzheimer disease","volume":"281","author":"Kinghorn","year":"2006","journal-title":"J. Biol. Chem."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"865","DOI":"10.1111\/j.1582-4934.2011.01394.x","article-title":"Activators and inhibitors of the plasminogen system in Alzheimer\u2019s disease","volume":"16","author":"Barker","year":"2012","journal-title":"J. Cell. Mol. Med."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"3937","DOI":"10.1523\/JNEUROSCI.20-11-03937.2000","article-title":"The plasmin system is induced by and degrades amyloidbeta aggregates","volume":"20","author":"Tucker","year":"2000","journal-title":"J. Neurosci."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"172","DOI":"10.1007\/s00018-022-04185-6","article-title":"Neuroserpin, a crucial regulator for axogenesis, synaptic modelling and cell\u2013cell interactions in the pathophysiology of neurological disease","volume":"79","author":"Godinez","year":"2022","journal-title":"Cell. Mol. Life Sci."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"303","DOI":"10.1111\/j.1471-4159.2009.05894.x","article-title":"Plasminogen activator activity is inhibited while neuroserpin is up-regulated in the Alzheimer disease brain","volume":"109","author":"Fabbro","year":"2009","journal-title":"J. Neurochem."},{"key":"ref_98","doi-asserted-by":"crossref","unstructured":"Lee, T.W., Tsang, V.W., and Birch, N.P. (2015). Physiological and pathological roles of tissue plasminogen activator and its inhibitor neuroserpin in the nervous system. Front. Cell. Neurosci., 9.","DOI":"10.3389\/fncel.2015.00396"},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1038\/s41514-024-00145-5","article-title":"Switch of innate to adaptative immune responses in the brain of patients with Alzheimer\u2019s disease correlates with tauopathy progression","volume":"10","author":"Costa","year":"2024","journal-title":"NPJ Aging"},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"25992","DOI":"10.1074\/jbc.270.43.25992","article-title":"Pigment epithelium-derived factor behaves like a noninhibitory serpin. Neurotrophic activity does not require the serpin reactive loop","volume":"270","author":"Becerra","year":"1995","journal-title":"J. Biol. Chem."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"484","DOI":"10.2174\/0929866527666191230103739","article-title":"Renin-Angiotensin System and Alzheimer\u2019s Disease Pathophysiology: From the Potential Interactions to Therapeutic Perspectives","volume":"27","author":"Ribeiro","year":"2020","journal-title":"Protein Pept. Lett."},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"2236","DOI":"10.1016\/j.tjnut.2024.05.012","article-title":"Association of Egg Intake With Alzheimer\u2019s Dementia Risk in Older Adults: The Rush Memory and Aging Project","volume":"154","author":"Pan","year":"2024","journal-title":"J. Nutr."},{"key":"ref_103","doi-asserted-by":"crossref","unstructured":"Margara-Escudero, H.J., Zamora-Ros, R., de Villasante, I., Crous-Bou, M., Chirlaque, M.-D., Amiano, P., Mar, J., Barricarte, A., Ardanaz, E., and Huerta, J.M. (2022). Association Between Egg Consumption and Dementia Risk in the EPIC-Spain Dementia Cohort. Front. Nutr., 9.","DOI":"10.3389\/fnut.2022.827307"},{"key":"ref_104","doi-asserted-by":"crossref","unstructured":"Igbinigie, P.O., Chen, R., Tang, J., Dregan, A., Yin, J., Acharya, D., Nadim, R., Chen, A., Bai, Z., and Amirabdollahian, F. (2024). Association between Egg Consumption and Dementia in Chinese Adults. Nutrients, 16.","DOI":"10.3390\/nu16193340"},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"476","DOI":"10.3945\/ajcn.116.146753","article-title":"Association of dietary cholesterol and egg intakes with the risk of incident dementia or Alzheimer disease: The Kuopio Ischaemic Heart Disease Risk Factor Study","volume":"105","author":"Ylilauri","year":"2017","journal-title":"Am. J. Clin. Nutr."},{"key":"ref_106","doi-asserted-by":"crossref","unstructured":"Kritz-Silverstein, D., and Bettencourt, R. (2024). Egg Consumption and 4-Year Change in Cognitive Function in Older Men andWomen: The Rancho Bernardo Study. Nutrients, 16.","DOI":"10.3390\/nu16162765"},{"key":"ref_107","doi-asserted-by":"crossref","unstructured":"Gao, R., Yang, Z., Yan, W., Du, W., Zhou, Y., and Zhu, F. (2022). Protein intake from different sources and cognitive decline over 9 years in community-dwelling older adults. Front. Public Health, 10.","DOI":"10.3389\/fpubh.2022.1016016"}],"container-title":["Biomolecules"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2218-273X\/15\/8\/1085\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T18:16:49Z","timestamp":1760033809000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2218-273X\/15\/8\/1085"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,7,27]]},"references-count":107,"journal-issue":{"issue":"8","published-online":{"date-parts":[[2025,8]]}},"alternative-id":["biom15081085"],"URL":"https:\/\/doi.org\/10.3390\/biom15081085","relation":{},"ISSN":["2218-273X"],"issn-type":[{"type":"electronic","value":"2218-273X"}],"subject":[],"published":{"date-parts":[[2025,7,27]]}}}