{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T22:53:11Z","timestamp":1790635991795,"version":"4.1.0"},"reference-count":171,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2026,6,11]],"date-time":"2026-06-11T00:00:00Z","timestamp":1781136000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"\u201cRamon and Cajal Research Program\u201d, Spanish Ministry of Science, Innovation and Universities","award":["RYC-2006-002658"],"award-info":[{"award-number":["RYC-2006-002658"]}]},{"award":["RYC-2006-002658"],"award-info":[{"award-number":["RYC-2006-002658"]}],"id":[{"id":"https:\/\/ror.org\/05r0vyz12","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biomolecules"],"abstract":"<jats:p>Alzheimer\u2019s disease (AD) is a multifactorial neurodegenerative disorder characterized by amyloid-\u03b2 (A\u03b2) and the accumulation of tau in the brain, which triggers robust innate immune responses. Growing evidence indicates that neuroinflammation contributes to AD progression by overactivating microglia through the release of cytokines and chemokines. In general, chemokines can disrupt neuronal communication and promote blood\u2013brain barrier permeability. Peripheral immune cells are mobilized into the brain by a gradient of chemokines. These processes link peripheral immune responses with substantial T-cell infiltration into the CNS parenchyma, leptomeninges and cerebrospinal fluid of both AD mice and AD patients. This finding underscores the relevance of the adaptive immune system, particularly T and B cells, in AD neuropathology. T-cell infiltration into the brain can influence amyloid clearance through chemokine signalling. However, chemokines play a critical role in AD by either promoting or suppressing disease progression. The infiltration of peripheral T and B cells into the brain parenchyma can exacerbate neuronal loss, yet it may also exert neuroprotective effects. Despite the presence of CD4+ and CD8+ T cells in postmortem brains of AD patients, debate continues about their role in AD brains, in terms of whether they are protective or detrimental. Understanding the complex role of chemokines in controlling innate and adaptive immune responses by modulating neuron\u2013glia interactions (involving astrocytes and microglia) may provide novel therapeutic approaches for AD. Targeting chemokine signalling or treating with drugs that can prevent the recruitment of immune cells may be promising strategies for treating AD neuropathology. Therapies that prevent the overactivation of T cells in the brain could lead to protective strategies against AD. In fact, regulatory T cells (Tregs) could delay the onset of cognitive symptoms, because they suppress inflammation and slow the accumulation of A\u03b2 plaques and p-Tau in the brain. Complementary strategies, such as photobiomodulation, nanoparticle, and T-cell-based approaches, could mitigate AD progression in patients.<\/jats:p>","DOI":"10.3390\/biom16060855","type":"journal-article","created":{"date-parts":[[2026,6,11]],"date-time":"2026-06-11T06:57:17Z","timestamp":1781161037000},"page":"855","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["The Immune-Chemokine Axis in Alzheimer\u2019s Disease: Roles of Adaptive Immune System in Neuroinflammation and Disease Progression"],"prefix":"10.3390","volume":"16","author":[{"given":"Jos\u00e9 Joaqu\u00edn","family":"Merino","sequence":"first","affiliation":[{"name":"Facultad de Farmacia, Departamento de Farmacolog\u00eda, Farmacognosia y Bot\u00e1nica, Universidad Complutense de Madrid (UCM), 28040 Madrid, Spain"},{"name":"Instituto Pluridisciplinar, Universidad Complutense de Madrid (UCM), 28040 Madrid, Spain"},{"name":"Grupo de Medicina Regenerativa, Instituto de Investigaci\u00f3n Sanitaria Hospital 12 de Octubre (imas12), 28041 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jos\u00e9 Julio","family":"Rodr\u00edguez-Arellano","sequence":"additional","affiliation":[{"name":"Functional Neuroanatomy Group, IKERBASQUE, Basque Foundation for Science, 48009 Bilbao, Spain"},{"name":"Department of Neurosciences, Medical Faculty, University of the Basque Country (UPV\/EHU), 48940 Leioa, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1157-5590","authenticated-orcid":false,"given":"Xavier","family":"Busquets","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular Cell Biomedicine, Department of Biology, Faculty of Medicine, University of the Balearic Islands, 07122 Palma de Mallorca, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6796-809X","authenticated-orcid":false,"given":"Isabel","family":"\u00c1lvarez-Vicente","sequence":"additional","affiliation":[{"name":"Instituto Cajal, Consejo Superior de Investigaciones Cient\u00edficas (CSIC), 28002 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mar\u00eda Eugenia","family":"Caba\u00f1a-Mu\u00f1oz","sequence":"additional","affiliation":[{"name":"Centro de Rehabilitaci\u00f3n Oral Multidisciplinar\u00eda (CIROM), 30001 Murcia, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5019-0434","authenticated-orcid":false,"given":"Ana Isabel","family":"Flores","sequence":"additional","affiliation":[{"name":"Grupo de Medicina Regenerativa, Instituto de Investigaci\u00f3n Sanitaria Hospital 12 de Octubre (imas12), 28041 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2274-5949","authenticated-orcid":false,"given":"Adolfo Toledano","family":"Gasca","sequence":"additional","affiliation":[{"name":"Instituto Cajal, Consejo Superior de Investigaciones Cient\u00edficas (CSIC), 28002 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,6,11]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"429","DOI":"10.1038\/nri2565","article-title":"Regulation of innate immune responses in the brain","volume":"9","author":"Rivest","year":"2009","journal-title":"Nat. Rev. Immunol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"260","DOI":"10.1002\/glia.10153","article-title":"Microglia and inflammatory mechanisms in the clearance of amyloid beta peptide","volume":"40","author":"Rogers","year":"2002","journal-title":"Glia"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"333","DOI":"10.1016\/S0197-0186(01)00040-7","article-title":"Microglial chemotaxis, activation, and phagocytosis of amyloid beta-peptide as linked phenomena in Alzheimer\u2019s disease","volume":"39","author":"Rogers","year":"2001","journal-title":"Neurochem. Int."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"115199","DOI":"10.1016\/j.intimp.2025.115199","article-title":"Unraveling APOE4: The dual role in CNS and peripheral inflammation in Alzheimer\u2019s disease","volume":"163","author":"Li","year":"2025","journal-title":"Int. Immunopharmacol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"321","DOI":"10.1038\/s41577-024-01104-7","article-title":"Neuroinflammation in Alzheimer disease","volume":"25","author":"Heneka","year":"2025","journal-title":"Nat. Rev. Immunol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"275","DOI":"10.1111\/imcb.12843","article-title":"Chemokines in neurodegenerative diseases","volume":"103","author":"Vida","year":"2025","journal-title":"Immunol. Cell Biol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"870","DOI":"10.2174\/1567205014666170317113606","article-title":"Impact of Cytokines and Chemokines on Alzheimer\u2019s Disease Neuropathological Hallmarks","volume":"14","author":"Domingues","year":"2017","journal-title":"Curr. Alzheimer Res."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"e70341","DOI":"10.1111\/jnc.70341","article-title":"Innate Immune Tolerance Regulates Microglia Response to A\u03b2 Oligomers","volume":"170","author":"Valerio","year":"2026","journal-title":"J. Neurochem."},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Ana, B. (2024). Aged-Related Changes in Microglia and Neurodegenerative Diseases: Exploring the Connection. Biomedicines, 12.","DOI":"10.20944\/preprints202405.0722.v1"},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"McGroarty, J., Salinas, S., Evans, H., Jimenez, B., Tran, V., Kadavakollu, S., Vashist, A., and Atluri, V. (2025). Inflammasome-Mediated Neuroinflammation: A Key Driver in Alzheimer\u2019s Disease Pathogenesis. Biomolecules, 15.","DOI":"10.3390\/biom15050676"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"689","DOI":"10.1038\/s41582-021-00549-x","article-title":"Peripheral and central immune system crosstalk in Alzheimer disease\u2014A research prospectus","volume":"17","author":"Bettcher","year":"2021","journal-title":"Nat. Rev. Neurol."},{"key":"ref_12","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_13","doi-asserted-by":"crossref","first-page":"115374","DOI":"10.1016\/j.expneurol.2025.115374","article-title":"Microglial dysfunction in Alzheimer\u2019s disease: Mechanisms, emerging therapies, and future directions","volume":"392","author":"Azmal","year":"2025","journal-title":"Exp. Neurol."},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Bai, H., and Zhang, Q. (2021). Activation of NLRP3 Inflammasome and Onset of Alzheimer\u2019s Disease. Front. Immunol., 12.","DOI":"10.3389\/fimmu.2021.701282"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"25424823251326044","DOI":"10.1177\/25424823251326044","article-title":"Targeting the chemokine-microglia nexus: A novel strategy for modulating neuroinflammation in Alzheimer\u2019s disease","volume":"9","author":"Xu","year":"2025","journal-title":"J. Alzheimer\u2019s Dis. Rep."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"E1316","DOI":"10.1073\/pnas.1525466113","article-title":"The adaptive immune system restrains Alzheimer\u2019s disease pathogenesis by modulating microglial function","volume":"113","author":"Marsh","year":"2016","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"157","DOI":"10.1038\/s41582-020-00435-y","article-title":"Neuroinflammation and microglial activation in Alzheimer disease: Where do we go from here?","volume":"17","author":"Leng","year":"2021","journal-title":"Nat. Rev. Neurol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1489","DOI":"10.1038\/s41593-023-01415-3","article-title":"Infiltrating CD8+ T cells exacerbate Alzheimer\u2019s disease pathology in a 3D human neuroimmune axis model","volume":"26","author":"Jorfi","year":"2023","journal-title":"Nat. Neurosci."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"205","DOI":"10.1038\/s41586-019-1362-5","article-title":"Single-cell analysis reveals T cell infiltration in old neurogenic niches","volume":"571","author":"Dulken","year":"2019","journal-title":"Nature"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"e13511","DOI":"10.1111\/acel.13511","article-title":"Insights into T-cell dysfunction in Alzheimer\u2019s disease","volume":"20","author":"Dai","year":"2021","journal-title":"Aging Cell"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"399","DOI":"10.1038\/s41586-019-1895-7","article-title":"Clonally Expanded CD8 T Cells Patrol the Cerebrospinal Fluid in Alzheimer\u2019s Disease","volume":"577","author":"Gate","year":"2020","journal-title":"Nature"},{"key":"ref_22","first-page":"17","article-title":"Photobiomodulation modulates mitochondrial energy metabolism and ameliorates neurological damage in an APP\/PS1 mouse model of Alzheimer\u2019s disease","volume":"5","author":"Chen","year":"2025","journal-title":"Alzheimer\u2019s Res. Ther."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"153","DOI":"10.1016\/j.immuni.2023.12.001","article-title":"An exhausted-like microglial population accumulates in aged and APOE4 genotype Alzheimer\u2019s brains","volume":"57","author":"Millet","year":"2024","journal-title":"Immunity"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1031","DOI":"10.1038\/s41556-026-01910-2","article-title":"Characterizing the metabolomes of microglia, astrocytes and neurons in ageing and Alzheimer\u2019s brains","volume":"28","author":"Yu","year":"2026","journal-title":"Nat. Cell Biol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"403","DOI":"10.2174\/1567205013666151116125714","article-title":"Effects of CX3CR1 and Fractalkine Chemokines in Amyloid Beta Clearance and p-Tau Accumulation in Alzheimer\u2019s Disease (AD) Rodent Models: Is Fractalkine a Systemic Biomarker for AD?","volume":"13","author":"Merino","year":"2016","journal-title":"Curr. Alzheimer Res."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"489","DOI":"10.1016\/j.neuron.2006.01.022","article-title":"Bone marrow-derived microglia play a critical role in restricting senile plaque formation in Alzheimer\u2019s disease","volume":"49","author":"Simard","year":"2006","journal-title":"Neuron"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"60","DOI":"10.1186\/s12987-024-00557-1","article-title":"Cellular and molecular mechanisms of the blood-brain barrier dysfunction in neurodegenerative diseases","volume":"21","author":"Chen","year":"2024","journal-title":"Fluids Barriers CNS"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"20","DOI":"10.1016\/j.jneuroim.2008.04.023","article-title":"Chemokine signaling and integrin activation in lymphocyte migration into the inflamed brain","volume":"198","author":"Constantin","year":"2008","journal-title":"J. Neuroimmunol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"105466","DOI":"10.1016\/j.ebiom.2024.105466","article-title":"The role of neuroinflammation in cerebral amyloid an-giopathy","volume":"110","author":"Voigt","year":"2024","journal-title":"eBioMedicine"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1261","DOI":"10.1073\/pnas.0805453106","article-title":"Selective targeting of perivascular macrophages for clearance of beta-amyloid in cerebral amyloid angiopathy","volume":"27","author":"Hawkes","year":"2009","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1758","DOI":"10.1084\/jem.21211insight5","article-title":"Peripheral macrophages not ADept at amyloid clearance","volume":"212","author":"Jay","year":"2015","journal-title":"J. Exp. Med."},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Kierdorf, K., Katzmarski, N., Haas, C.A., and Prinz, M. (2013). Bone marrow cell recruitment to the brain in the absence of irradiation or parabiosis bias. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0058544"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"447","DOI":"10.1038\/s41586-024-07501-1","article-title":"A disease-associated gene desert directs macrophage inflammation through ETS2","volume":"630","author":"Stankey","year":"2024","journal-title":"Nature"},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Nie, W., Yue, Y., and Hu, J. (2025). The role of monocytes and macrophages in the progression of Alzheimer\u2019s disease. Front. Immunol., 16.","DOI":"10.3389\/fimmu.2025.1590909"},{"key":"ref_35","first-page":"8342","article-title":"Neuroinflammation in Alzheimer\u2019s disease: Chemokines produced by astrocytes and chemokine receptors","volume":"7","author":"Liu","year":"2014","journal-title":"Int. J. Clin. Exp. Pathol."},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Xie, C., Aman, Y., Adriaanse, B.A., Cader, M.Z., Plun-Favreau, H., Xiao, J., and Fang, E.F. (2020). Culprit or Bystander: Defective Mitophagy in Alzheimer\u2019s Disease. Front. Cell Dev. Biol., 7.","DOI":"10.3389\/fcell.2019.00391"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"377","DOI":"10.1007\/s00401-016-1596-3","article-title":"Innate phagocytosis by peripheral blood monocytes is altered in Alzheimer\u2019s disease","volume":"132","author":"Gu","year":"2016","journal-title":"Acta Neuropathol."},{"key":"ref_38","doi-asserted-by":"crossref","unstructured":"Song, Y., Shu, S., Zeng, X., Xia, M., Liu, J., and Li, L. (2026). Microglial Innate Immune Memory: Implications and Research Advances in Central Nervous System Disorders. Curr. Issues Mol. Biol., 48.","DOI":"10.3390\/cimb48040426"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"480","DOI":"10.1007\/BF03401753","article-title":"Amyloid-beta induces chemokine secretion and monocyte migration across a human blood-brain barrier model","volume":"4","author":"Fiala","year":"1998","journal-title":"Mol. Med."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"70201","DOI":"10.1002\/trc2.70201","article-title":"Acute anti-A\u03b2 antibody exposure induces microglial changes and significantly alters chemokine signaling","volume":"12","author":"Foley","year":"2026","journal-title":"Alzheimer\u2019s Dement."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"1321","DOI":"10.3233\/JAD-210692","article-title":"The Correlation of Tau Levels with Blood Monocyte Count in Patients with Alzheimer\u2019s Disease","volume":"85","author":"Sun","year":"2022","journal-title":"J. Alzheimer\u2019s Dis. JAD"},{"key":"ref_42","first-page":"12","article-title":"Bone marrow-derived macrophages from aged rats are more responsive to inflammatory stimuli","volume":"9","author":"Barrett","year":"2015","journal-title":"J. Neuroinflamm."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"2708","DOI":"10.1126\/sciadv.adu2708","article-title":"Understanding monocyte-driven neuroinflammation in Alzheimer\u2019s disease using human cortical organoid microphysiological systems","volume":"22","author":"Tian","year":"2025","journal-title":"Sci. Adv."},{"key":"ref_44","doi-asserted-by":"crossref","unstructured":"Kays, M., Kelly, A., McGinnis, F., Woods, C., Herron, E., Brown, C., and Coulibaly, A.P. (2025). Neutrophils from Alzheimer\u2019s disease mice fail to phagocytose debris and show altered release of immune modulators with age. Front. Immunol., 20.","DOI":"10.1101\/2025.04.21.649766"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"e088677","DOI":"10.1002\/alz.088677","article-title":"The cerebrospinal fluid Neutrophil gelatinase-associated lipocalin (NGAL) concentration in Alzheimer\u2019s Disease (AD)","volume":"20","author":"Doroszkiewicz","year":"2025","journal-title":"Alzheimer\u2019s Dement."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"1573","DOI":"10.1177\/13872877251352411","article-title":"Alzheimer\u2019s Disease Neuroimaging Initiative. LCN2 of cerebrospinal fluid: A potential biomarker for diagnosis and disease progression in Alzheimer\u2019s disease","volume":"106","author":"Zhang","year":"2025","journal-title":"J. Alzheimer\u2019s Dis."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1186\/s13195-021-00955-9","article-title":"Plasma Lipocalin 2 in Alzheimer\u2019s disease: Potential utility in the differential diagnosis and relationship with other biomarkers","volume":"13","author":"Hermann","year":"2022","journal-title":"Alzheimer\u2019s Res. Ther."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"13958","DOI":"10.1007\/s12035-025-05186-9","article-title":"17\u03b2-Trenbolone Increases the Release of Lipocalin 2 via the Brain-Liver Axis and Causes Alzheimer\u2019s Disease-Like Symptoms in CSDS-Induced Mice","volume":"62","author":"Zuo","year":"2025","journal-title":"Mol. Neurobiol."},{"key":"ref_49","doi-asserted-by":"crossref","unstructured":"Custodia, A., Aramburu-N\u00fa\u00f1ez, M., Rodr\u00edguez-Arrizabalaga, M., P\u00edas-Peleteiro, J.M., V\u00e1zquez-V\u00e1zquez, L., Camino-Casti\u00f1eiras, J., Aldrey, J.M., Castillo, J., Ouro, A., and Sobrino, T. (2023). Biomarkers Assessing Endothelial Dysfunction in Alzheimer\u2019s Disease. Cells, 12.","DOI":"10.3390\/cells12060962"},{"key":"ref_50","doi-asserted-by":"crossref","unstructured":"Gericke, C., Mallone, A., Engelhardt, B., Nitsch, R.M., and Ferretti, M.T. (2020). Oligomeric Forms of Human Amyloid-Beta (1-42) Inhibit Antigen Presentation. Front. Immunol., 5.","DOI":"10.3389\/fimmu.2020.01029"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"210","DOI":"10.1016\/j.neurobiolaging.2007.06.007","article-title":"Amyloid beta peptide promotes differentiation of pro-inflammatory human myeloid dendritic cells","volume":"30","author":"Ciaramella","year":"2009","journal-title":"Neurobiol. Aging"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"3549","DOI":"10.1182\/blood-2011-02-338780","article-title":"CCL18 differentiates dendritic cells in tolerogenic cells able to prime regulatory T cells in healthy subjects","volume":"29","author":"Azzaoui","year":"2011","journal-title":"Blood"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"168","DOI":"10.2174\/187152710791011982","article-title":"Mechanisms of mononuclear phagocyte recruitment in Alzheimer\u2019s disease","volume":"9","author":"Hickman","year":"2010","journal-title":"CNS Neurol. Disord. Drug Targets"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"432","DOI":"10.1038\/nm1555","article-title":"Ccr2 deficiency impairs microglial accumulation and accelerates progression of Alzheimer-like disease","volume":"13","author":"Toft","year":"2007","journal-title":"Nat. Med."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"6208","DOI":"10.1523\/JNEUROSCI.0299-11.2011","article-title":"CC chemokine receptor 2 deficiency aggravates cognitive impairments and amyloid pathology in a transgenic mouse model of Alzheimer\u2019s disease","volume":"31","author":"Naert","year":"2011","journal-title":"J. Neurosci."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"163","DOI":"10.1016\/j.cyto.2010.10.008","article-title":"Depletion of CXCR2 inhibits gamma-secretase activity and amyloid-beta production in a murine model of Alzheimer\u2019s disease","volume":"53","author":"Bakshi","year":"2011","journal-title":"Cytokine"},{"key":"ref_57","doi-asserted-by":"crossref","unstructured":"Jorda, A., Alvarez-Gamez, K., Campo-Palacio, I., Campos-Campos, J., Colmena, C., Singh, S.K., Miralles, M.J.C., Aldasoro, C., Aldasoro, M., and Valles, S.L. (2026). Inflammatory Mediators of Alzheimer\u2019s Disease Characterized in a Mouse Model (APP\/PS1). NeuroSci, 7.","DOI":"10.3390\/neurosci7010023"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"453","DOI":"10.7150\/ijbs.26703","article-title":"Changes in Chemokines and Chemokine Receptors Expression in a Mouse Model of Alzheimer\u2019s Disease","volume":"15","author":"Jorda","year":"2019","journal-title":"Int. J. Biol. Sci."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"197","DOI":"10.1016\/j.neurobiolaging.2017.10.021","article-title":"Alpha7 nicotinic acetylcholine receptor-specific agonist DMXBA (GTS-21) attenuates A\u03b2 accumulation through suppression of neuronal \u03b3-secretase activity and promotion of microglial amyloid-\u03b2 phagocytosis and ameliorates cognitive impairment in a mouse model of Alzheimer\u2019s disease","volume":"62","author":"Takata","year":"2018","journal-title":"Neurobiol. Aging"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"11984","DOI":"10.18632\/oncotarget.7453","article-title":"CCR5 deficiency accelerates lipopolysaccharide-induced astrogliosis, amyloid-beta deposit and impaired memory function","volume":"7","author":"Hwang","year":"2016","journal-title":"Oncotarget"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"2549","DOI":"10.2353\/ajpath.2010.100265","article-title":"CX3CR1 deficiency alters microglial activation and reduces beta-amyloid deposition in two Alzheimer\u2019s disease mouse models","volume":"177","author":"Lee","year":"2010","journal-title":"Am. J. Pathol."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"17091","DOI":"10.1523\/JNEUROSCI.4403-10.2010","article-title":"CX3CR1 in microglia regulates brain amyloid deposition through selective protofibrillar amyloid-\u03b2 phagocytosis","volume":"30","author":"Liu","year":"2010","journal-title":"J. Neurosci. Off. J. Soc. Neurosci."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1016\/S0002-9440(10)65542-3","article-title":"Immunohistochemical study of the \u03b2-chemokine receptors CCR3 and CCR5 and their ligands in normal and Alzheimer\u2019s disease brains","volume":"153","author":"Xia","year":"1998","journal-title":"Am. J. Pathol."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"356","DOI":"10.1016\/j.nlm.2009.04.003","article-title":"CCR5 deficiency induces astrocyte activation, Abeta deposit and impaired memory function","volume":"92","author":"Lee","year":"2009","journal-title":"Neurobiol. Learn. Mem."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"365","DOI":"10.1172\/JCI66771","article-title":"CXCR3 promotes plaque formation and behavioral deficits in an Alzheimer\u2019s disease model","volume":"125","author":"Krauthausen","year":"2015","journal-title":"J. Clin. Investig."},{"key":"ref_66","doi-asserted-by":"crossref","unstructured":"Guedes, J.R., Lao, T., Cardoso, A.L., and El Khoury, J. (2018). Roles of Microglial and Monocyte Chemokines and Their Receptors in Regulating Alzheimer\u2019s Disease-Associated Amyloid-\u03b2 and Tau Pathologies. Front. Neurol., 9.","DOI":"10.3389\/fneur.2018.00549"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"eabe4601","DOI":"10.1126\/sciadv.abe4601","article-title":"Aging-associated deficit in CCR7 is linked to worsened glymphatic function, cognition, neuroinflammation, and \u03b2-amyloid pathology","volume":"7","author":"Herz","year":"2021","journal-title":"Sci. Adv."},{"key":"ref_68","doi-asserted-by":"crossref","unstructured":"Shabbir, U., Arshad, M.S., Sameen, A., and Oh, D.H. (2021). Crosstalk between Gut and Brain in Alzheimer\u2019s Disease: The Role of Gut Microbiota Modulation Strategies. Nutrients, 13.","DOI":"10.3390\/nu13020690"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"116109","DOI":"10.1016\/j.celrep.2025.116109","article-title":"Amyloid-\u03b2-driven Alzheimer\u2019s disease reshapes the colonic immune system in mice","volume":"44","author":"Makhijani","year":"2025","journal-title":"Cell Rep."},{"key":"ref_70","doi-asserted-by":"crossref","unstructured":"Abbaoui, A., Fatoba, O., and Yamashita, T. (2023). Meningeal T cells function in the central nervous system homeostasis and neurodegenerative diseases. Front. Cell. Neurosci., 17.","DOI":"10.3389\/fncel.2023.1181071"},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"36","DOI":"10.1186\/s12979-024-00443-2","article-title":"Terminally differentiated effector memory T cells associate with cognitive and AD-related biomarkers in an aging-based community cohort","volume":"21","author":"Winford","year":"2024","journal-title":"Immun. Ageing"},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"1020","DOI":"10.1056\/NEJM200010053431407","article-title":"T-cell function and migration. Two sides of the same coin","volume":"343","author":"Mackay","year":"2000","journal-title":"N. Engl. J. Med."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"113180","DOI":"10.1016\/j.celrep.2023.113180","article-title":"Effector memory T cells induce innate inflammation by triggering DNA damage and a non-canonical STING pathway in dendritic cells","volume":"42","author":"Meibers","year":"2023","journal-title":"Cell Rep."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"e70380","DOI":"10.1002\/iid3.70380","article-title":"New Perspective: Bench to Bedside Evidence of the Role of CD8+ T Cells in Alzheimer\u2019s Disease","volume":"14","author":"Peng","year":"2026","journal-title":"Immun. Inflamm. Dis."},{"key":"ref_75","doi-asserted-by":"crossref","unstructured":"Cao, Y., Tang, K., Ma, P., Zhang, R., Yang, Y., Li, T., Zhang, Y., and Peng, X. (2025). The role of peripheral innate immune cells in Alzheimer\u2019s disease progression. Front. Immunol., 16.","DOI":"10.3389\/fimmu.2025.1616939"},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"5028","DOI":"10.1016\/j.cell.2022.11.019","article-title":"Cerebrospinal fluid immune dysregulation during healthy brain aging and cognitive impairment","volume":"185","author":"Piehl","year":"2022","journal-title":"Cell"},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"e14548","DOI":"10.1002\/alz.14548","article-title":"Exploring the role of T cells in Alzheimer\u2019s and other neurodegenerative diseases: Emerging therapeutic insights from the T Cells in the Brain symposium","volume":"21","author":"Elyaman","year":"2025","journal-title":"Alzheimer\u2019s Dement."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"14","DOI":"10.1186\/s44477-026-00020-5","article-title":"Spilling the T: T cells in tauopathy mechanisms, disease progression, and therapeutic horizons","volume":"2","author":"Bosch","year":"2026","journal-title":"Mol. Neurodegener. Adv."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"457","DOI":"10.1002\/ana.21379","article-title":"Localizing central nervous system immune surveillance: Meningeal antigen-presenting cells activate T cells during experimental autoimmune encephalomyelitis","volume":"65","author":"Imitola","year":"2009","journal-title":"Ann. Neurol."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"12518","DOI":"10.1038\/s41598-026-38351-8","article-title":"Unique phenotypic and T cell receptor characteristics of CD8+ T cells accumulated in the brains of Alzheimer\u2019s disease mice","volume":"16","author":"Zhihuan","year":"2026","journal-title":"Sci. Rep."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"162","DOI":"10.1159\/000081856","article-title":"Expression of TH1\/TH2-related chemokine receptors on peripheral T cells and correlation with clinical disease activity in patients with multiple sclerosis","volume":"52","author":"Nakajima","year":"2004","journal-title":"Eur. Neurol."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"587","DOI":"10.1038\/s41423-020-0465-0","article-title":"Antigen presentation by dendritic cells and their instruction of CD4+ T helper cell responses","volume":"17","author":"Hilligan","year":"2020","journal-title":"Cell Mol. Immunol."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"323","DOI":"10.1038\/s41590-025-02401-6","article-title":"Clonal CD8+ T\u2009cells populate the leptomeninges and coordinate with immune cells in human degenerative brain diseases","volume":"27","author":"Hobson","year":"2026","journal-title":"Nat. Immunol."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"473","DOI":"10.1038\/s41586-020-03116-4","article-title":"Gut-licensed IFN\u03b3+ NK cells drive LAMP1+TRAIL+ anti-inflammatory astrocytes","volume":"590","author":"Sanmarco","year":"2021","journal-title":"Nature"},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"9458","DOI":"10.1038\/s41467-025-64503-x","article-title":"Stage-specific roles of clonally expanded CD8+ T cells in regulating amyloid pathology in Alzheimer\u2019s disease models","volume":"27","author":"Ohyagi","year":"2025","journal-title":"Nat. Commun."},{"key":"ref_86","doi-asserted-by":"crossref","unstructured":"Xu, R., Song, W., and Zhang, X. (2026). Interleukin-6, CD8+ T cells, and Alzheimer\u2019s disease: Unraveling neuroimmune crosstalk via genetic and mechanistic insights. Front. Aging Neurosci., 18.","DOI":"10.3389\/fnagi.2026.1767927"},{"key":"ref_87","doi-asserted-by":"crossref","unstructured":"Fani Maleki, A., and Rivest, S. (2019). Innate Immune Cells: Monocytes, Monocyte-Derived Macrophages and Microglia as Therapeutic Targets for Alzheimer\u2019s Disease and Multiple Sclerosis. Front. Cell. Neurosci., 13.","DOI":"10.3389\/fncel.2019.00355"},{"key":"ref_88","doi-asserted-by":"crossref","unstructured":"Si, Y., Zhang, Y., and Yang, Q. (2025). Aging induces T cells with distinct transcriptomic profiles and functions in brain- associated tissues. Front. Immunol., 16.","DOI":"10.3389\/fimmu.2025.1619196"},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"106461","DOI":"10.1016\/j.nbd.2024.106461","article-title":"T cell infiltration mediates neurodegeneration and cognitive decline in Alzheimer\u2019s disease","volume":"193","author":"Zeng","year":"2024","journal-title":"Neurobiol. Dis."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"124","DOI":"10.4062\/biomolther.2025.199","article-title":"Adaptive Immunity and Alzheimer\u2019s Disease: Dual Roles in Neurodegeneration and Neuroprotection with Therapeutic Implications","volume":"34","author":"Ahn","year":"2026","journal-title":"Biomol. Ther."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"941","DOI":"10.1016\/j.neurobiolaging.2005.05.021","article-title":"Telomere Shortening in T Lymphocytes of Older Individuals With Down Syndrome and Dementia","volume":"27","author":"Jenkins","year":"2006","journal-title":"Neurobiol. Aging"},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1016\/S0197-4580(02)00043-X","article-title":"Telomere Shortening in T Cells Correlates with Alzheimer\u2019s Disease Status","volume":"24","author":"Panossian","year":"2003","journal-title":"Neurobiol. Aging"},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"52","DOI":"10.1016\/j.jneuroim.2011.11.005","article-title":"Immune profiling of Alzheimer patients","volume":"242","author":"Larbi","year":"2012","journal-title":"J. Neuroimmunol."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"415","DOI":"10.1172\/JCI200318104","article-title":"Increased T cell reactivity to amyloid beta protein in older humans and patients with Alzheimer disease","volume":"112","author":"Monsonego","year":"2003","journal-title":"J. Clin. Investig."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"1533","DOI":"10.2174\/011570159X350611250303044527","article-title":"Deciphering T Cell Dynamics in Alzheimer\u2019s Disease Pathogenesis: Insights and Implications","volume":"23","author":"Yang","year":"2025","journal-title":"Curr. Neuropharmacol."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"1206","DOI":"10.1038\/nm.3670","article-title":"Interleukin-8 (CXCL8) production is a signatory T cell effector function of human newborn infants","volume":"20","author":"Gibbons","year":"2014","journal-title":"Nat. Med."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"109574","DOI":"10.1016\/j.celrep.2021.109574","article-title":"IL-17 triggers the onset of cognitive and synaptic deficits in early stages of Alzheimer\u2019s disease","volume":"36","author":"Brigas","year":"2021","journal-title":"Cell Rep."},{"key":"ref_98","doi-asserted-by":"crossref","unstructured":"Shi, Y., Wei, B., Li, L., Wang, B., and Sun, M. (2022). Th17 cells and inflammation in neurological disorders: Possible mechanisms of action. Front. Immunol., 13.","DOI":"10.3389\/fimmu.2022.932152"},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"3328","DOI":"10.1523\/JNEUROSCI.5321-06.2007","article-title":"Involvement of interferon-gamma in microglial-mediated loss of dopaminergic neurons","volume":"27","author":"Mount","year":"2007","journal-title":"J. Neurosci. Off. J. Soc. Neurosci."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1186\/s13024-023-00692-7","article-title":"Amyloid-\u03b2 specific regulatory T cells attenuate Alzheimer\u2019s disease pathobiology in APP\/PS1 mice","volume":"18","author":"Yeapuri","year":"2023","journal-title":"Mol. Neurodegener."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"1160","DOI":"10.1038\/s41593-025-01955-w","article-title":"Microglia activation orchestrates CXCL10-mediated CD8+ T cell recruitment to promote aging-related white matter degeneration","volume":"28","author":"Groh","year":"2025","journal-title":"Nat. Neurosci."},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"1468","DOI":"10.1038\/s41593-024-01682-8","article-title":"T cell-mediated microglial activation triggers myelin pathology in a mouse model of amyloidosis","volume":"27","author":"Kedia","year":"2024","journal-title":"Nat. Neurosci."},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"534","DOI":"10.1016\/j.neuron.2014.12.068","article-title":"Il10 deficiency rebalances innate immunity to mitigate Alzheimer-like pathology","volume":"85","author":"Doty","year":"2015","journal-title":"Neuron"},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"211","DOI":"10.1016\/j.bbi.2016.02.009","article-title":"T-cell brain infiltration and immature antigen-presenting cells in transgenic models of Alzheimer\u2019s disease-like cerebral amyloidosis","volume":"54","author":"Ferretti","year":"2016","journal-title":"Brain Behav. Immun."},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"216","DOI":"10.1111\/j.1600-065X.2012.01140.x","article-title":"T-cell trafficking in the central nervous system","volume":"248","author":"Sallusto","year":"2012","journal-title":"Immunol. Rev."},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"2185","DOI":"10.1038\/s41467-021-22479-4","article-title":"Therapeutic B-cell depletion reverses progression of Alzheimer\u2019s disease","volume":"12","author":"Kim","year":"2021","journal-title":"Nat. Commun."},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"784","DOI":"10.1523\/JNEUROSCI.1523-19.2019","article-title":"Convergence between Microglia and Peripheral Macrophages Phenotype during Development and Neuroinflammation","volume":"40","author":"Grassivaro","year":"2020","journal-title":"J. Neurosci. Off. J. Soc. Neurosci."},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"3529","DOI":"10.4103\/NRR.NRR-D-24-00793","article-title":"Alzheimer\u2019s disease and the immune system: The emerging role of TEMRA cells","volume":"1","author":"Winford","year":"2025","journal-title":"Neural Regen. Res."},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"15779","DOI":"10.1038\/s41598-023-42708-8","article-title":"T cell exhaustion is associated with cognitive status and amyloid accumulation in Alzheimer\u2019s disease","volume":"13","author":"Grayson","year":"2023","journal-title":"Sci. Rep."},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"5642","DOI":"10.1002\/alz.13136","article-title":"Early \u03b2-amyloid accumulation in the brain is associated with peripheral T cell alterations","volume":"19","author":"Gericke","year":"2023","journal-title":"Alzheimer\u2019s Dement."},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"38","DOI":"10.1186\/s13024-024-00726-8","article-title":"Adaptive immune changes associate with clinical progression of Alzheimer\u2019s disease","volume":"19","author":"Kamermans","year":"2024","journal-title":"Mol. Neurodegener."},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"938","DOI":"10.1038\/s41590-020-0711-8","article-title":"Peripherally induced brain tissue-resident memory CD8(+) T cells mediate protection against CNS infection","volume":"21","author":"Urban","year":"2020","journal-title":"Nat. Immunol."},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"1735","DOI":"10.1038\/s41590-023-01604-z","article-title":"CXCR6 orchestrates brain CD8+ T cell residency and limits mouse Alzheimer\u2019s disease pathology","volume":"24","author":"Su","year":"2023","journal-title":"Nat. Immunol."},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"1152","DOI":"10.1038\/s41590-025-02198-4","article-title":"Granzyme K+ CD8 T cells slow tauopathy progression by targeting microglia","volume":"26","author":"Mason","year":"2025","journal-title":"Nat. Immunol."},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"3364","DOI":"10.1093\/brain\/awaf167","article-title":"Altered T-cell reactivity in the early stages of Alzheimer\u2019s disease","volume":"148","author":"Rickenbach","year":"2025","journal-title":"Brain"},{"key":"ref_116","first-page":"6","article-title":"Breaking immune tolerance by targeting Foxp3(+) regulatory T cells mitigates Alzheimer\u2019s disease pathology","volume":"18","author":"Baruch","year":"2015","journal-title":"Nat. Commun."},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1186\/s40478-015-0251-x","article-title":"Reduced \u03b2-amyloid pathology in an APP transgenic mouse model of Alzheimer\u2019s disease lacking functional B and T cells","volume":"3","author":"Suter","year":"2015","journal-title":"Acta Neuropathol. Commun."},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1159\/000486200","article-title":"Extravascular CD3+ T cells in brains of Alzheimer disease patients correlate with tau but not with amyloid pathology: An immunohistochemical study","volume":"18","author":"Merlini","year":"2018","journal-title":"Neurodegener. Dis."},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"438","DOI":"10.1111\/imm.12103","article-title":"CD4 T cells in immunity and immunotherapy of Alzheimer\u2019s disease","volume":"139","author":"Monsonego","year":"2013","journal-title":"Immunology"},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"879","DOI":"10.1016\/j.immuni.2022.03.018","article-title":"Concerted type I interferon signaling in microglia and neural cells promotes memory impairment associated with amyloid \u03b2 plaques","volume":"55","author":"Roy","year":"2022","journal-title":"Immunity"},{"key":"ref_121","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1016\/j.bbi.2020.05.070","article-title":"CD8+ T-cells infiltrate Alzheimer\u2019s disease brains and regulate neuronal- and synapse-related gene expression in APP-PS1 transgenic mice","volume":"89","author":"Unger","year":"2020","journal-title":"Brain Behav. Immun."},{"key":"ref_122","doi-asserted-by":"crossref","first-page":"e70187","DOI":"10.1111\/cns.70187","article-title":"CD4-Derived Double-Negative T Cells Ameliorate Alzheimer\u2019s Disease-Like Phenotypes in the 5\u00d7FAD Mouse Model","volume":"31","author":"Xie","year":"2025","journal-title":"CNS Neurosci. Ther."},{"key":"ref_123","doi-asserted-by":"crossref","first-page":"524","DOI":"10.1016\/j.immuni.2026.02.004","article-title":"Immunity in Alzheimer\u2019s disease: From mechanisms to therapies","volume":"59","author":"Chen","year":"2026","journal-title":"Immunity"},{"key":"ref_124","doi-asserted-by":"crossref","first-page":"e13092","DOI":"10.1111\/cpr.13092","article-title":"T-cell infiltration, contribution and regulation in the central nervous system post-traumatic injury","volume":"54","author":"Xu","year":"2021","journal-title":"Cell Prolif."},{"key":"ref_125","doi-asserted-by":"crossref","first-page":"eadl4458","DOI":"10.1126\/scisignal.adl4458","article-title":"Restraining neuroinflammation in Alzheimer\u2019s disease","volume":"16","author":"Foley","year":"2023","journal-title":"Sci. Signal."},{"key":"ref_126","doi-asserted-by":"crossref","first-page":"2241","DOI":"10.4049\/jimmunol.1200947","article-title":"IFN-\u03b3 Production by amyloid \u03b2-specific Th1 cells promotes microglial activation and increases plaque burden in a mouse model of Alzheimer\u2019s disease","volume":"190","author":"Browne","year":"2013","journal-title":"J. Immunol."},{"key":"ref_127","doi-asserted-by":"crossref","first-page":"102068","DOI":"10.1016\/j.arr.2023.102068","article-title":"Alzheimer\u2019s disease as a viral disease: Revisiting the infectious hypothesis","volume":"91","author":"Bruno","year":"2023","journal-title":"Ageing Res. Rev."},{"key":"ref_128","doi-asserted-by":"crossref","first-page":"2791","DOI":"10.1172\/JCI66827","article-title":"Fc\u03b3RIIb mediates amyloid-\u03b2 neurotoxicity and memory impairment in Alzheimer\u2019s disease","volume":"123","author":"Kam","year":"2013","journal-title":"J. Clin. Investig."},{"key":"ref_129","doi-asserted-by":"crossref","unstructured":"Lophatananon, A., Carr, M., Mcmillan, B., Dobson, C., Itshki, R., Parisi, R., Ashcroft, D.M., and Muir, K.R. (2023). The association of herpes zoster and influenza vaccinations with the risk of developing dementia: A population-based cohort study within the UK Clinical Practice Research Datalink. BMC Public Health, 23.","DOI":"10.1186\/s12889-023-16768-4"},{"key":"ref_130","doi-asserted-by":"crossref","first-page":"388","DOI":"10.1038\/s41398-025-03639-2","article-title":"Viral infections and the risk of neurodegenerative diseases: A comprehensive meta-analysis and systematic review","volume":"15","author":"Liu","year":"2025","journal-title":"Transl. Psychiatry"},{"key":"ref_131","doi-asserted-by":"crossref","first-page":"64","DOI":"10.1186\/s12974-025-03666-2","article-title":"Toxoplasma gondii drives myeloid immune cell recruitment to amyloid plaques in Alzheimer\u2019s model mice","volume":"23","author":"Yanes","year":"2026","journal-title":"J. Neuroinflamm."},{"key":"ref_132","doi-asserted-by":"crossref","first-page":"148589","DOI":"10.1016\/j.brainres.2023.148589","article-title":"Alzheimer\u2019s disease: The role of T lymphocytes in neuroinflammation and neurodegeneration","volume":"1821","author":"Asamu","year":"2023","journal-title":"Brain Res."},{"key":"ref_133","doi-asserted-by":"crossref","first-page":"104778","DOI":"10.1016\/j.cellimm.2023.104778","article-title":"Differential roles of regulatory T cells in Alzheimer\u2019s disease","volume":"393\u2013394","author":"Jafarzadeh","year":"2023","journal-title":"Cell. Immunol."},{"key":"ref_134","doi-asserted-by":"crossref","first-page":"224","DOI":"10.1002\/jmv.1890330403","article-title":"Latent herpes simplex virus type 1 in normal and Alzheimer\u2019s disease brains","volume":"33","author":"Jamieson","year":"1991","journal-title":"J. Med. Virol."},{"key":"ref_135","doi-asserted-by":"crossref","unstructured":"Zhao, Y., Li, X., Dong, W., Zhu, H., Wang, S., Xu, M., Xu, Y., Liu, M., Duan, J., and Liu, Y. (2026). Integrated Single-Cell Multi-Omics Analysis Reveals That a CD8+ TPex-Monocyte Interaction Axis Coordinates Immune Infiltration in Alzheimer\u2019s Disease. Int. J. Mol. Sci., 27.","DOI":"10.3390\/ijms27041783"},{"key":"ref_136","doi-asserted-by":"crossref","unstructured":"Guo, L., Li, X., Gould, T., Wang, Z.-Y., and Cao, W. (2023). T cell aging and Alzheimer\u2019s disease. Front. Immunol., 14.","DOI":"10.3389\/fimmu.2023.1154699"},{"key":"ref_137","first-page":"1850","article-title":"T-regulatory cells and extracellular vesicles in Alzheimer\u2019s disease: New therapeutic concepts and hypotheses","volume":"1","author":"Mendes","year":"2025","journal-title":"Brain Res."},{"key":"ref_138","doi-asserted-by":"crossref","first-page":"8788","DOI":"10.1038\/s41598-019-45433-3","article-title":"The Characterization of Regulatory T-Cell Profiles in Alzheimer\u2019s Disease and Multiple Sclerosis","volume":"19","author":"Ciccocioppo","year":"2019","journal-title":"Sci. Rep."},{"key":"ref_139","doi-asserted-by":"crossref","first-page":"4987","DOI":"10.1038\/s41467-019-12980-2","article-title":"CXCR3 enables recruitment and site-specific bystander activation of memory CD8+ T cells","volume":"10","author":"Maurice","year":"2019","journal-title":"Nat. Commun."},{"key":"ref_140","doi-asserted-by":"crossref","first-page":"1605","DOI":"10.1084\/jem.20102101","article-title":"Chemokine receptor CXCR3 facilitates CD8 (+) T cell differentiation into short-lived effector cells leading to memory degeneration","volume":"208","author":"Kurachi","year":"2011","journal-title":"J. Exp. Med."},{"key":"ref_141","doi-asserted-by":"crossref","first-page":"3737","DOI":"10.1038\/s41467-026-72262-6","article-title":"Type I interferon drives T cell responses to amyloid beta in the central nervous system","volume":"17","author":"Michel","year":"2026","journal-title":"Nat. Commun."},{"key":"ref_142","doi-asserted-by":"crossref","first-page":"38221","DOI":"10.1038\/s41598-025-22137-5","article-title":"The involvement of microglia and the CXCL16-CXCR6 axis in the recruitment of CD8+ T cells to an amyloidogenic mouse brain","volume":"31","author":"Zattoni","year":"2025","journal-title":"Sci. Rep."},{"key":"ref_143","doi-asserted-by":"crossref","first-page":"3034","DOI":"10.1093\/brain\/awaf288","article-title":"T cells turn in Alzheimer\u2019s disease","volume":"148","author":"Skelly","year":"2025","journal-title":"Brain"},{"key":"ref_144","doi-asserted-by":"crossref","first-page":"656","DOI":"10.1016\/j.bbi.2020.06.027","article-title":"Downregulation of synapse-associated protein expression and loss of homeostatic microglial control in cerebrospinal fluid of infectious patients with delirium and patients with Alzheimer\u2019s disease","volume":"89","author":"Verbeek","year":"2020","journal-title":"Brain Behav. Immun."},{"key":"ref_145","doi-asserted-by":"crossref","first-page":"2076","DOI":"10.2353\/ajpath.2009.090059","article-title":"Interferon-{gamma} differentially affects Alzheimer\u2019s disease pathologies and induces neurogenesis in triple transgenic-AD mice","volume":"175","author":"Mastrangelo","year":"2009","journal-title":"Am. J. Pathol."},{"key":"ref_146","doi-asserted-by":"crossref","first-page":"96","DOI":"10.1093\/cei\/uxac078","article-title":"Regulatory T-cell therapy approaches","volume":"211","author":"McCallion","year":"2023","journal-title":"Clin. Exp. Immunol."},{"key":"ref_147","doi-asserted-by":"crossref","first-page":"1664","DOI":"10.3389\/fimmu.2024.1457189","article-title":"Regulatory T cells: Masterminds of immune equilibrium and future therapeutic innovations","volume":"15","author":"Ge","year":"2024","journal-title":"Front. Immunol."},{"key":"ref_148","doi-asserted-by":"crossref","first-page":"64","DOI":"10.1186\/s12974-023-02702-3","article-title":"Regulatory T cells decrease C3-positive reactive astrocytes in Alzheimer-like pathology","volume":"20","author":"Matta","year":"2023","journal-title":"J. Neuroinflamm."},{"key":"ref_149","doi-asserted-by":"crossref","first-page":"2610559","DOI":"10.1080\/07853890.2025.2610559","article-title":"Targeting CXCL8 in post-traumatic stress disorder and Alzheimer\u2019s disease: Insights from cross-disorder molecular analysis","volume":"58","author":"Liao","year":"2026","journal-title":"Ann. Med."},{"key":"ref_150","doi-asserted-by":"crossref","first-page":"117779","DOI":"10.1016\/j.bcp.2026.117779","article-title":"Cobrotoxin mitigates neuroinflammation and cognitive impairment by suppressing CD8+ T cell-microglia interactions in male 5 \u00d7 FAD mice","volume":"247","author":"Li","year":"2026","journal-title":"Biochem. Pharmacol."},{"key":"ref_151","doi-asserted-by":"crossref","first-page":"146","DOI":"10.1186\/s13195-025-01791-x","article-title":"Low-dose interleukin-2 in patients with mild to moderate Alzheimer\u2019s disease: A randomized clinical trial","volume":"17","author":"Faridar","year":"2025","journal-title":"Alzheimer\u2019s Res. Ther."},{"key":"ref_152","doi-asserted-by":"crossref","first-page":"6333","DOI":"10.1523\/JNEUROSCI.0829-08.2008","article-title":"Complement C3 deficiency leads to accelerated amyloid beta plaque deposition and neurodegeneration and modulation of the microglia\/macrophage phenotype in amyloid precursor protein transgenic mice","volume":"28","author":"Maier","year":"2008","journal-title":"J. Neurosci. Off. J. Soc. Neurosci."},{"key":"ref_153","doi-asserted-by":"crossref","unstructured":"Monteiro, R., Dunn, J.T., Rodriguez, G., Fisher, D.W., and Dong, H. (2026). Targeting central immune signaling enhances the effects of methylphenidate in alleviating apathy-like behavior in 5xFAD mice. Sci. Rep.","DOI":"10.1038\/s41598-026-49172-0"},{"key":"ref_154","doi-asserted-by":"crossref","first-page":"356","DOI":"10.1007\/s12035-025-05652-4","article-title":"Valacyclovir Mitigates Amyloid Plaque Deposition, P-Tau Aggregation, and Neuroinflammation in Streptozotocin induced Alzheimer\u2019s Disease Rat Model","volume":"63","author":"Tripathi","year":"2026","journal-title":"Mol. Neurobiol."},{"key":"ref_155","doi-asserted-by":"crossref","unstructured":"Lim, L. (2024). Modifying Alzheimer\u2019s disease pathophysiology with photobiomodulation: Model, evidence, and future with EEG-guided intervention. Front. Neurol., 15.","DOI":"10.3389\/fneur.2024.1407785"},{"key":"ref_156","doi-asserted-by":"crossref","first-page":"6601","DOI":"10.1007\/s12035-017-0852-4","article-title":"Brain Photobiomodulation Therapy: A Narrative Review","volume":"55","author":"Salehpour","year":"2018","journal-title":"Mol. Neurobiol."},{"key":"ref_157","doi-asserted-by":"crossref","first-page":"776","DOI":"10.7150\/thno.120374","article-title":"Neuro-lymphaphotonics opens new horizons of the future technologies for the therapy of brain diseases","volume":"16","author":"Liu","year":"2026","journal-title":"Theranostics"},{"key":"ref_158","doi-asserted-by":"crossref","first-page":"100185","DOI":"10.1016\/j.tjpad.2025.100185","article-title":"Brain photobiomodulation: A potential treatment in Alzheimer\u2019s and Parkinson\u2019s diseases","volume":"12","author":"Blivet","year":"2025","journal-title":"J. Prev. Alzheimer\u2019s Dis."},{"key":"ref_159","doi-asserted-by":"crossref","first-page":"190","DOI":"10.1038\/s41392-025-02253-4","article-title":"Mitochondria in oxidative stress, inflammation and aging: From mechanisms to therapeutic advances","volume":"10","author":"Xu","year":"2025","journal-title":"Signal Transduct. Target. Ther."},{"key":"ref_160","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1007\/s10103-022-03692-z","article-title":"Photobiomodulation for Alzheimer\u2018s disease: Photoelectric coupling effect on attenuating A\u03b2 neurotoxicity","volume":"38","author":"Tian","year":"2023","journal-title":"Lasers Med. Sci."},{"key":"ref_161","doi-asserted-by":"crossref","unstructured":"Li, B., Golovynska, I., Stepanov, Y.V., Golovynskyi, S., Golovynskyi, A., Kolesnik, D., Stepanova, L.I., Lai, P., Lin, F., and Qu, J. (2025). Transcranial photobiomodulation therapy with 808\u2009nm light changes expression of genes and proteins associated with neuroprotection, neuroinflammation, oxidative stress, and Alzheimer disease: Whole RNA sequencing of mouse cortex and hippocampus. PLoS ONE, 20.","DOI":"10.1371\/journal.pone.0326881"},{"key":"ref_162","doi-asserted-by":"crossref","first-page":"114","DOI":"10.1186\/s13195-024-01484-x","article-title":"Photobiomodulation in experimental models of Alzheimer disease: State-of-the-art and translational perspectives","volume":"16","author":"Huang","year":"2024","journal-title":"Alzheimer\u2019s Res. Ther."},{"key":"ref_163","doi-asserted-by":"crossref","first-page":"113021","DOI":"10.1016\/j.jphotobiol.2024.113021","article-title":"Near-infrared laser diode mitigates A\u03b21\u201342-induced neurodegeneration in cortical neurons","volume":"259","author":"Kim","year":"2024","journal-title":"J. Photochem. Photobiol. B"},{"key":"ref_164","doi-asserted-by":"crossref","unstructured":"Pickart, L., and Margolina, A. (2018). Regenerative and Protective Actions of the GHK-Cu Peptide in the Light of the New Gene Data. Int. J. Mol. Sci., 19.","DOI":"10.3390\/ijms19071987"},{"key":"ref_165","doi-asserted-by":"crossref","unstructured":"Cao, S., Shi, X., Chen, Y., Liu, T., Hu, J., Dong, X., Chen, H., Dai, J., and Yin, H. (2025). Gut Microbiota-Targeted Photobiomodulation Ameliorates Alzheimer\u2019s Pathology via the Gut-Brain Axis: Comparable Efficacy to Transcranial Irradiation. Microorganisms, 13.","DOI":"10.3390\/microorganisms13122659"},{"key":"ref_166","doi-asserted-by":"crossref","unstructured":"Salehpour, F., Khademi, M., Bragin, D.E., and DiDuro, J.O. (2022). Photobiomodulation Therapy and the Glymphatic System: Promising Applications for Augmenting the Brain Lymphatic Drainage System. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms23062975"},{"key":"ref_167","doi-asserted-by":"crossref","unstructured":"Nairuz, T., Heo, J.C., Park, H.J., and Lee, J.H. (2025). Photobiomodulation at 660 nm Alleviates Alzheimer Disease Pathology Through Amyloid-\u03b2 Reduction and SIRT1 Upregulation in the Hippocampus of 5xFAD Mice. Int. J. Mol. Sci., 26.","DOI":"10.3390\/ijms26199569"},{"key":"ref_168","doi-asserted-by":"crossref","unstructured":"Semyachkina-Glushkovskaya, O., Klimova, M., Iskra, T., Bragin, D., Abdurashitov, A., Dubrovsky, A., Khorovodov, A., Terskov, A., Blokhina, I., and Lezhnev, N. (2021). Transcranial Photobiomodulation of Clearance of Beta-Amyloid from the Mouse Brain: Effects on the Meningeal Lymphatic Drainage and Blood Oxygen Saturation of the Brain. Oxygen Transport to Tissue XLII; Advances in Experimental Medicine and Biology, Springer International Publishing.","DOI":"10.1007\/978-3-030-48238-1_9"},{"key":"ref_169","doi-asserted-by":"crossref","unstructured":"Gaggi, N.L., Parincu, Z., Peterson, A., O\u2019Brien, C., Kam, K., Tural, U., Ayappa, I., Varga, A.W., Iosifescu, D.V., and Osorio, R.S. (2025). Enhancing sleep, wakefulness, and cognition with transcranial photobiomodulation: A systematic review. Front. Behav. Neurosci., 19.","DOI":"10.3389\/fnbeh.2025.1542462"},{"key":"ref_170","doi-asserted-by":"crossref","first-page":"2086","DOI":"10.4103\/1673-5374.262573","article-title":"Remote photobiomodulation: An emerging strategy for neuroprotection","volume":"14","author":"Gordon","year":"2019","journal-title":"Neural Regen. Res."},{"key":"ref_171","doi-asserted-by":"crossref","first-page":"13872877261443973","DOI":"10.1177\/13872877261443973","article-title":"J Home-based transcranial photobiomodulation improves cognitive function in mild cognitive impairment due to Alzheimer\u2019s disease: A randomized, double-blind, placebo-controlled confirmatory trial","volume":"23","author":"Chun","year":"2026","journal-title":"J. Alzheimer\u2019s Dis."}],"container-title":["Biomolecules"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2218-273X\/16\/6\/855\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,6,11]],"date-time":"2026-06-11T07:32:01Z","timestamp":1781163121000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2218-273X\/16\/6\/855"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,6,11]]},"references-count":171,"journal-issue":{"issue":"6","published-online":{"date-parts":[[2026,6]]}},"alternative-id":["biom16060855"],"URL":"https:\/\/doi.org\/10.3390\/biom16060855","relation":{},"ISSN":["2218-273X"],"issn-type":[{"value":"2218-273X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,6,11]]}}}