{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,10]],"date-time":"2026-07-10T16:12:32Z","timestamp":1783699952776,"version":"3.55.0"},"reference-count":73,"publisher":"MDPI AG","issue":"14","license":[{"start":{"date-parts":[[2026,7,10]],"date-time":"2026-07-10T00:00:00Z","timestamp":1783641600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Plan for NRRP Complementary Investments D34 Health"},{"name":"Fondazione Anticorpi Antifosfolipidi (APS) Onlus, Naples"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Human anti-\u03b1Gal antibodies (Abs), known for their marked polyreactivity, have been detected bound to the gray matter of the brains of Alzheimer\u2019s disease (AD) patients, although their targets were unclear. Since \u03b1Gal is a strictly xenogenic antigen absent in humans, this observation raised questions regarding the nature of the structures recognized by these antibodies. In this study, we investigated their potential interaction with gangliosides\u2014glycan structures that are highly abundant in the central nervous system. Using a competitive inhibition ELISA, serum profiles of anti-\u03b1Gal Abs isotypes and their indirect cross-reactivity with selected soluble gangliosides were analyzed in AD patients and healthy subjects (HSs). AD patients showed reduced levels of anti-\u03b1Gal IgG and IgM, but increased IgA compared to HSs. Notably, pre-incubation with GM1, GM2, or GD1b did not reduce \u03b1Gal\u2013HSA binding in HS sera. In contrast, in AD sera, pre-incubation with GD1b reduced residual \u03b1Gal\u2013HSA binding for all antibody isotypes; additionally, GM1 inhibited IgM binding, and GM2 inhibited IgA binding. These results should therefore be interpreted as competitive inhibition patterns consistent with ganglioside-associated cross-reactivity rather than as direct evidence of antibody binding to immobilized gangliosides. Overall, the findings provide preliminary evidence that, in AD sera, a fraction of \u03b1Gal\u2013HSA-reactive antibodies can be competitively inhibited by selected gangliosides. This observation supports the presence of an altered humoral anti-carbohydrate signature in AD and identifies neuronal gangliosides as plausible candidate autologous targets that may help explain the previously reported binding of anti-\u03b1Gal Abs to gray matter. However, given the indirect nature of the assay, these data should be considered hypothesis-generating and require confirmation by direct binding approaches.<\/jats:p>","DOI":"10.3390\/ijms27146190","type":"journal-article","created":{"date-parts":[[2026,7,10]],"date-time":"2026-07-10T15:13:36Z","timestamp":1783696416000},"page":"6190","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Anti-Alpha-Gal Antibodies Against Gangliosides: Preliminary Data on a New Autoimmune Target in Alzheimer\u2019s Disease Patients"],"prefix":"10.3390","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8198-8799","authenticated-orcid":false,"given":"Filippo","family":"Naso","sequence":"first","affiliation":[{"name":"Biocompatibility Innovation S.r.l., Via Lorenzo de Antoni, n.17\/19, 35042 Este, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alessandro","family":"Gandaglia","sequence":"additional","affiliation":[{"name":"Biocompatibility Innovation S.r.l., Via Lorenzo de Antoni, n.17\/19, 35042 Este, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2278-6492","authenticated-orcid":false,"given":"Giulio","family":"Sturaro","sequence":"additional","affiliation":[{"name":"Biocompatibility Innovation S.r.l., Via Lorenzo de Antoni, n.17\/19, 35042 Este, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2037-673X","authenticated-orcid":false,"given":"Alessio","family":"Lepore","sequence":"additional","affiliation":[{"name":"Department of Medicine and Health Sciences \u2018V. Tiberio\u2019, University of Molise, 86100 Campobasso, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5924-3694","authenticated-orcid":false,"given":"Alessia","family":"Arcaro","sequence":"additional","affiliation":[{"name":"Department of Medicine and Health Sciences \u2018V. Tiberio\u2019, University of Molise, 86100 Campobasso, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6704-3115","authenticated-orcid":false,"given":"Fabrizio","family":"Gentile","sequence":"additional","affiliation":[{"name":"Department of Medicine and Health Sciences \u2018V. Tiberio\u2019, University of Molise, 86100 Campobasso, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6138-5640","authenticated-orcid":false,"given":"Alfonso","family":"Di Costanzo","sequence":"additional","affiliation":[{"name":"Department of Medicine and Health Sciences \u2018V. Tiberio\u2019, University of Molise, 86100 Campobasso, Italy"},{"name":"Molise Regional Health Authority (ASREM), 86100 Campobasso, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0158-3039","authenticated-orcid":false,"given":"Antonella","family":"Angiolillo","sequence":"additional","affiliation":[{"name":"Department of Medicine and Health Sciences \u2018V. Tiberio\u2019, University of Molise, 86100 Campobasso, Italy"},{"name":"Molise Regional Health Authority (ASREM), 86100 Campobasso, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,7,10]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"353","DOI":"10.1126\/science.1072994","article-title":"The Amyloid Hypothesis of Alzheimer\u2019s Disease: Progress and Problems on the Road to Therapeutics","volume":"297","author":"Hardy","year":"2002","journal-title":"Science"},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Gonz\u00e1lez-Sanmiguel, J., Schuh, C.M.A.P., Mu\u00f1oz-Montesino, C., Contreras-Kallens, P., Aguayo, L.G., and Aguayo, S. (2020). Complex Interaction between Resident Microbiota and Misfolded Proteins: Role in Neuroinflammation and Neurodegeneration. Cells, 9.","DOI":"10.3390\/cells9112476"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"388","DOI":"10.1016\/S1474-4422(15)70016-5","article-title":"Neuroinflammation in Alzheimer\u2019s disease","volume":"14","author":"Heneka","year":"2015","journal-title":"Lancet Neurol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"358","DOI":"10.1038\/nrn3880","article-title":"Immune Attack: The Role of Inflammation in Alzheimer Disease","volume":"16","author":"Heppner","year":"2015","journal-title":"Nat. Rev. Neurosci."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"719","DOI":"10.1016\/j.jalz.2016.02.010","article-title":"Neuroinflammation in Alzheimer\u2019s Disease: Current Evidence and Future Directions","volume":"12","author":"Calsolaro","year":"2016","journal-title":"Alzheimer\u2019s Dement."},{"key":"ref_6","first-page":"575","article-title":"Inflammation as a central mechanism in Alzheimer\u2019s disease","volume":"4","author":"Kinney","year":"2018","journal-title":"Alzheimers Dement."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"479","DOI":"10.1007\/s00401-013-1177-7","article-title":"The Amyloid Cascade-Inflammatory Hypothesis of Alzheimer Disease: Implications for Therapy","volume":"126","author":"McGeer","year":"2013","journal-title":"Acta Neuropathol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"321","DOI":"10.1038\/s41577-024-01104-7","article-title":"Neuroinflammation in Alzheimer\u2019s disease","volume":"25","author":"Heneka","year":"2025","journal-title":"Nat. Rev. Immunol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"38","DOI":"10.1186\/s12979-024-00445-0","article-title":"Neuroinflammation in Alzheimer\u2019s disease: Insights from peripheral immune cells","volume":"21","author":"Zhang","year":"2024","journal-title":"Immun. Ageing"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"297","DOI":"10.1016\/j.molimm.2021.12.009","article-title":"Imbalance in pro-inflammatory and anti-inflammatory cy-tokines milieu in B cells of children with autism","volume":"141","author":"Nadeem","year":"2022","journal-title":"Mol. Immunol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1186\/s13195-023-01218-5","article-title":"A peripheral signature of Alzheimer\u2019s disease featuring microbiota-gut-brain axis markers","volume":"15","author":"Marizzoni","year":"2023","journal-title":"Alzheimer\u2019s Res. Ther."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"75","DOI":"10.1016\/j.bbagen.2007.11.003","article-title":"The Galalpha1,3Galbeta1,4GlcNAc-R (Alpha-Gal) Epitope: A Carbohydrate of Unique Evolution and Clinical Relevance","volume":"1780","author":"Macher","year":"2008","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"674","DOI":"10.1111\/j.1440-1711.2005.01366.x","article-title":"The Alpha-Gal Epitope and the Anti-Gal Antibody in Xenotransplantation and in Cancer Immunotherapy","volume":"83","author":"Galili","year":"2005","journal-title":"Immunol. Cell Biol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"434","DOI":"10.1111\/imm.13297","article-title":"The Human Natural Anti-\u03b1Gal Antibody Targets Common Pathogens by Broad-Spectrum Polyreactivity","volume":"162","author":"Skeldal","year":"2021","journal-title":"Immunology"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"2796","DOI":"10.1097\/01.MIB.0000435437.76741.cb","article-title":"Lectin-Reactive Anti-\u03b1-Gal in Patients with Crohn\u2019s Disease: Correlation with Clinical Phenotypes","volume":"19","author":"Safaie","year":"2013","journal-title":"Inflamm. Bowel Dis."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"558","DOI":"10.1111\/dote.12356","article-title":"High Rate of Galactose-Alpha-1,3-Galactose Sensitization in Both Eosinophilic Esophagitis and Patients Undergoing Upper Endoscopy","volume":"29","author":"Burk","year":"2016","journal-title":"Dis. Esophagus"},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Angiolillo, A., Gandaglia, A., Arcaro, A., Carpi, A., Gentile, F., and Naso, F. (2021). Altered Blood Levels of Anti-Gal Antibodies in Alzheimer\u2019s Disease: A New Clue to Pathogenesis?. Life, 11.","DOI":"10.3390\/life11060538"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"589648","DOI":"10.1155\/2015\/589648","article-title":"Acceleration of Wound Healing by \u03b1-Gal Nanoparticles Interacting with the Natural Anti-Gal Antibody","volume":"2015","author":"Galili","year":"2015","journal-title":"J. Immunol. Res."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"2485","DOI":"10.1182\/blood.V82.8.2485.2485","article-title":"One Percent of Human Circulating B Lymphocytes Are Capable of Producing the Natural Anti-Gal Antibody","volume":"82","author":"Galili","year":"1993","journal-title":"Blood"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"187","DOI":"10.1007\/BF02703115","article-title":"Epitopes Recognized by Serum Anti-\u03b1-Galactoside Antibody Are Present on Brain Glycoproteins in Man","volume":"18","author":"Jaison","year":"1993","journal-title":"J. Biosci."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"6387","DOI":"10.1021\/cr2002917","article-title":"Sphingolipid and glycosphingolipid metabolic pathways in the era of sphingolipidomics","volume":"111","author":"Merrill","year":"2011","journal-title":"Chem. Rev."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"688","DOI":"10.1038\/nrm2977","article-title":"Revitalizing Membrane Rafts: New Tools and Insights","volume":"11","author":"Simons","year":"2010","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Sipione, S., Monyror, J., Galleguillos, D., Steinberg, N., and Kadam, V. (2020). Gangliosides in the Brain: Physiology. Pathophysiology and Therapeutic Applications. Front. Neurosci., 14.","DOI":"10.3389\/fnins.2020.572965"},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Guo, Z. (2023). Ganglioside GM1 and the Central Nervous System. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms24119558"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"4530255","DOI":"10.1155\/2024\/4530255","article-title":"Gangliosides as Therapeutic Targets for Diseases","volume":"2024","author":"Inci","year":"2024","journal-title":"J. Lipids."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"183233","DOI":"10.1016\/j.bbamem.2020.183233","article-title":"A\u03b2-Ganglioside Interactions in the Pathogenesis of Alzheimer\u2019s Disease","volume":"1862","author":"Matsuzaki","year":"2020","journal-title":"Biochim. Biophys. Acta Biomembr."},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Rudajev, V., and Novotny, J. (2020). The Role of Lipid Environment in Ganglioside GM1-Induced Amyloid \u03b2 Aggregation. Membranes, 10.","DOI":"10.3390\/membranes10090226"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"171","DOI":"10.1111\/j.1471-4159.2004.02849.x","article-title":"Structural membrane alterations in Alzheimer brains found to be as-sociated with regional disease development; increased density of gangliosides GM1 and GM2 and loss of cholesterol in detergent-resistant membrane domains","volume":"92","author":"Blennow","year":"2005","journal-title":"J. Neurochem."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"447","DOI":"10.1023\/B:NERE.0000013750.80925.25","article-title":"Alzheimer\u2019s Disease: NMR Studies of Asialo (GM1) and Trisialo (GT1b) Ganglioside Interactions with Abeta(1-40) Peptide in a Membrane Mimic Environment","volume":"29","author":"Mandal","year":"2004","journal-title":"Neurochem. Res."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"217","DOI":"10.1111\/jnc.15365","article-title":"Neuronally Expressed A-Series Gangliosides Are Sufficient to Prevent the Lethal Age-Dependent Phenotype in GM3-Only Expressing Mice","volume":"158","author":"McGonigal","year":"2021","journal-title":"J. Neurochem."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"95","DOI":"10.1016\/S0014-5793(96)01504-9","article-title":"The Interaction between Alzheimer Amyloid \u03b2(1-40) Peptide and Ganglioside GM1-Containing Membranes","volume":"402","author":"Surewicz","year":"1997","journal-title":"FEBS Lett."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"24985","DOI":"10.1074\/jbc.M100252200","article-title":"Cholesterol-Dependent Formation of GM1 Ganglioside-Bound Amyloid Beta-Protein, an Endogenous Seed for Alzheimer Amyloid","volume":"276","author":"Kakio","year":"2001","journal-title":"J. Biol. Chem."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1066","DOI":"10.1016\/j.jmb.2008.07.072","article-title":"Formation of Toxic A\u03b2(1-40) Fibrils on GM1 Ganglioside-Containing Membranes Mimicking Lipid Rafts: Polymorphisms in A\u03b2(1-40) Fibrils","volume":"382","author":"Okada","year":"2008","journal-title":"J. Mol. Biol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"6692","DOI":"10.1039\/C3CS60431D","article-title":"Differences between amyloid-\u03b2 aggregation in solution and on the membrane: Insights into elucidation of the mechanistic details of Alzheimer\u2019s disease","volume":"43","author":"Kotler","year":"2014","journal-title":"Chem. Soc. Rev."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"6433","DOI":"10.1021\/bi200771m","article-title":"Mechanism of Amyloid \u03b2-Protein Aggregation Mediated by GM1 Ganglioside Clusters","volume":"50","author":"Ikeda","year":"2011","journal-title":"Biochemistry"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"235","DOI":"10.1016\/0304-3940(88)90577-0","article-title":"Antibodies to Ganglioside GM1 in Patients with Alzheimer\u2019s Disease","volume":"86","author":"Chapman","year":"1988","journal-title":"Neurosci. Lett."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"274","DOI":"10.1177\/1533317508317816","article-title":"Antibodies against GM1 in Demented Patients","volume":"23","author":"Hatzifilippou","year":"2008","journal-title":"Am. J. Alzheimers Dis. Other Dement."},{"key":"ref_38","first-page":"S163","article-title":"The probable auto-antigenic role of lipids, anti-ganglioside antibodies, in the pathogenesis of Alzheimer\u2019s disease","volume":"42","author":"Koutsouraki","year":"2014","journal-title":"J. Neurol. Sci."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"1165","DOI":"10.3233\/JAD-140474","article-title":"Autoantibodies to GM1 and GQ1b\u03b1 are not biological markers of Alzheimer\u2019s disease","volume":"42","author":"Miura","year":"2014","journal-title":"J. Alzheimers Dis."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"7385","DOI":"10.1021\/bi0255874","article-title":"Interactions of Amyloid Beta-Protein with Various Gangliosides in Raft-like Membranes: Importance of GM1 Ganglioside-Bound Form as an Endogenous Seed for Alzheimer Amyloid","volume":"41","author":"Kakio","year":"2002","journal-title":"Biochemistry"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"5111","DOI":"10.1021\/jp207881k","article-title":"Formation of GM1 Ganglioside Clusters on the Lipid Membrane Containing Sphingomyeline and Cholesterol","volume":"116","author":"Mori","year":"2012","journal-title":"J. Phys. Chem. B"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"8085","DOI":"10.1021\/jp4029062","article-title":"Binding and Aggregation Mechanism of Amyloid \u03b2-Peptides onto the GM1 Ganglioside-Containing Lipid Membrane","volume":"117","author":"Hoshino","year":"2013","journal-title":"J. Phys. Chem. B"},{"key":"ref_43","first-page":"22711","article-title":"Raman Spectroscopy for Detecting Supported Planar Lipid Bilayers Composed of Ganglioside-GM1\/Sphingomyelin\/Cholesterol in the Presence of Amyloid-\u03b2","volume":"17","author":"Hu","year":"2015","journal-title":"Chem. Phys."},{"key":"ref_44","doi-asserted-by":"crossref","unstructured":"Manna, M., and Mukhopadhyay, C. (2013). Binding, Conformational Transition and Dimerization of Amyloid-\u03b2 Peptide on GM1-Containing Ternary Membrane: Insights from Molecular Dynamics Simulation. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0071308"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"851","DOI":"10.1111\/j.1471-4159.2010.06997.x","article-title":"Ganglioside-Mediated Aggregation of Amyloid \u03b2-Proteins (A\u03b2): Comparison between A\u03b2-(1-42) and A\u03b2-(1-40)","volume":"116","author":"Ogawa","year":"2011","journal-title":"J. Neurochem."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1523\/JNEUROSCI.4017-06.2007","article-title":"Passive Immunization with Anti-Ganglioside Antibodies Directly Inhibits Axon Regeneration in an Animal Model","volume":"27","author":"Lehmann","year":"2007","journal-title":"J. Neurosci."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"547","DOI":"10.1038\/cmi.2017.142","article-title":"Guillain-Barr\u00e9 Syndrome, Transverse Myelitis and Infectious Diseases","volume":"15","author":"Rojas","year":"2018","journal-title":"Cell Mol. Immunol."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1016\/S0022-510X(97)05392-6","article-title":"Antibodies to Fucogangliosides in Neurological Diseases","volume":"150","author":"Yuki","year":"1997","journal-title":"J. Neurol. Sci."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"296","DOI":"10.1016\/j.alit.2019.04.001","article-title":"Alpha-Gal-Containing Biologics and Anaphylaxis","volume":"68","author":"Chinuki","year":"2019","journal-title":"Allergol. Int."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"85","DOI":"10.1038\/nri724","article-title":"Epitope spreading in immune-mediated diseases","volume":"2","author":"Vanderlugt","year":"2002","journal-title":"Nat. Rev. Immunol."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"335","DOI":"10.1038\/nm1202","article-title":"Epitope Spreading Initiates in the CNS in Two Mouse Models of Multiple Sclerosis","volume":"11","author":"McMahon","year":"2005","journal-title":"Nat. Med."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"4683","DOI":"10.1016\/S0021-9258(18)61249-9","article-title":"Identification of Erythrocyte Gal Alpha 1-3Gal Glycosphingolipids with a Mouse Monoclonal Antibody, Gal-13","volume":"262","author":"Galili","year":"1987","journal-title":"J. Biol. Chem."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"313","DOI":"10.1038\/s41423-020-0388-9","article-title":"Physiology of Gangliosides and the Role of Antiganglioside Antibodies in Human Diseases","volume":"17","author":"Cutillo","year":"2020","journal-title":"Cell Mol. Immunol."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"e2123212119","DOI":"10.1073\/pnas.2123212119","article-title":"Genetic and Structural Basis of the Human Anti-\u03b1-Galactosyl Antibody Response","volume":"119","author":"Langley","year":"2022","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1016\/0008-6215(89)85087-6","article-title":"Synthesis, Structure, and Conformation of the Dilactone Derivative of GD1b Ganglioside","volume":"195","author":"Fronza","year":"1989","journal-title":"Carbohydr. Res."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"193618","DOI":"10.4061\/2011\/193618","article-title":"The Pathological Roles of Ganglioside Metabolism in Alzheimer\u2019s Disease: Effects of Gangliosides on Neurogenesis","volume":"2011","author":"Ariga","year":"2011","journal-title":"Int. J. Alzheimers Dis."},{"key":"ref_57","doi-asserted-by":"crossref","unstructured":"Sousa, J.A., Bernardes, C., Bernardo-Castro, S., Lino, M., Albino, I., Ferreira, L., Br\u00e1s, J., Guerreiro, R., T\u00e1buas-Pereira, M., and Baldeiras, I. (2023). Reconsidering the role of blood-brain barrier in Alzheimer\u2019s disease: From delivery to target. Front. Aging Neurosci., 15.","DOI":"10.3389\/fnagi.2023.1102809"},{"key":"ref_58","doi-asserted-by":"crossref","unstructured":"Kim, S., Jung, U.J., and Kim, S.R. (2025). The Crucial Role of the Blood-Brain Barrier in Neurodegenerative Diseases: Mechanisms of Disruption and Therapeutic Implications. J. Clin. Med., 14.","DOI":"10.3390\/jcm14020386"},{"key":"ref_59","doi-asserted-by":"crossref","unstructured":"Beltran-Velasco, A.I., and Clemente-Su\u00e1rez, V.J. (2025). Impact of Peripheral Inflammation on Blood\u2013Brain Barrier Dysfunction in Neurodegenerative Diseases. Int. J. Mol. Sci., 26.","DOI":"10.3390\/ijms26062440"},{"key":"ref_60","doi-asserted-by":"crossref","unstructured":"Fuller, J.P., Stavenhagen, J.B., and Teeling, J.L. (2014). New roles for Fc receptors in neurodegeneration\u2014The impact on immunotherapy for Alzheimer\u2019s disease. Front. Neurosci., 8.","DOI":"10.3389\/fnins.2014.00235"},{"key":"ref_61","doi-asserted-by":"crossref","unstructured":"Batista, A.F., Khan, K.A., Papavergi, M.-T., and Lemere, C.A. (2024). The Importance of Complement-Mediated Immune Signaling in Alzheimer\u2019s Disease Pathogenesis. Int. J. Mol. Sci., 25.","DOI":"10.3390\/ijms25020817"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1007\/BF00695495","article-title":"Lectin Histochemistry of Plaques and Tangles in Alzheimer\u2019s Disease","volume":"73","author":"Szumanska","year":"1987","journal-title":"Acta Neuropathol."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"814","DOI":"10.1006\/bbrc.1995.2694","article-title":"Affinity of Bandeiraea (Griffonia) Simplicifolia Lectin-I, Isolectin B4 for Gal Alpha 1\u2013>4 Gal Ligand","volume":"216","author":"Wu","year":"1995","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_64","doi-asserted-by":"crossref","unstructured":"Siew, J.J., and Chern, Y. (2018). Microglial Lectins in Health and Neurological Diseases. Front. Mol. Neurosci., 11.","DOI":"10.3389\/fnmol.2018.00158"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"6509","DOI":"10.1021\/bi00143a022","article-title":"Structural Characterization of X2 Glycosphingolipid, Its Extended Form, and Its Sialosyl Derivatives: Accumulation Associated with the Rare Blood Group p Phenotype","volume":"31","author":"Thorn","year":"1992","journal-title":"Biochemistry"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"317","DOI":"10.1111\/j.1365-2141.1986.tb02935.x","article-title":"The Natural Anti-Alpha-Galactosyl IgG on Human Normal Senescent Red Blood Cells","volume":"62","author":"Galili","year":"1986","journal-title":"BR. J. Haematol."},{"key":"ref_67","doi-asserted-by":"crossref","unstructured":"Lutz, H.U., and Bogdanova, A. (2013). Mechanisms Tagging Senescent Red Blood Cells for Clearance in Healthy Humans. Front. Physiol., 4.","DOI":"10.3389\/fphys.2013.00387"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"528","DOI":"10.1128\/iai.64.2.528-534.1996","article-title":"Bacterial Enzymes Can Add Galactose Alpha 1,3 to Human Erythrocytes and Create a Senescence-Associated Epitope","volume":"64","author":"Hamadeh","year":"1996","journal-title":"Infect. Immun."},{"key":"ref_69","doi-asserted-by":"crossref","unstructured":"Fibach, E. (2021). The Redox Balance and Membrane Shedding in RBC Production, Maturation, and Senescence. Front. Physiol., 12.","DOI":"10.3389\/fphys.2021.604738"},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"263","DOI":"10.1016\/j.jalz.2011.03.005","article-title":"The Diagnosis of Dementia Due to Alzheimer\u2019s Disease: Recommendations from the National Institute on Aging-Alzheimer\u2019s Association Workgroups on Diagnostic Guidelines for Alzheimer\u2019s Disease","volume":"7","author":"McKhann","year":"2011","journal-title":"Alzheimers Dement."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"189","DOI":"10.1016\/0022-3956(75)90026-6","article-title":"\u201cMini-Mental State\u201d. A Practical Method for Grading the Cognitive State of Patients for the Clinician","volume":"12","author":"Folstein","year":"1975","journal-title":"J. Psychiatr. Res."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"173","DOI":"10.1017\/S1041610297004870","article-title":"Clinical Dementia Rating: A Reliable and Valid Diagnostic and Staging Measure for Dementia of the Alzheimer Type","volume":"9","author":"Morris","year":"1997","journal-title":"Int. Psychogeriatr."},{"key":"ref_73","first-page":"20","article-title":"Alpha-Gal Syndrome: Implications for Cardiovascular Disease","volume":"2019","author":"Bianchi","year":"2019","journal-title":"Glob. Cardiol. Sci."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/27\/14\/6190\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,10]],"date-time":"2026-07-10T15:13:55Z","timestamp":1783696435000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/27\/14\/6190"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,7,10]]},"references-count":73,"journal-issue":{"issue":"14","published-online":{"date-parts":[[2026,7]]}},"alternative-id":["ijms27146190"],"URL":"https:\/\/doi.org\/10.3390\/ijms27146190","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,7,10]]}}}