{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,31]],"date-time":"2026-10-31T02:28:48Z","timestamp":1793413728661,"version":"4.5.0"},"reference-count":154,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2026,2,20]],"date-time":"2026-02-20T00:00:00Z","timestamp":1771545600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Neurology International"],"abstract":"<jats:p>Alzheimer\u2019s disease (AD) is traditionally defined by Amyloid-\u03b2 (A\u03b2) plaques and tau neurofibrillary tangles, yet these proteinopathies alone fail to explain disease heterogeneity, progression, and cognitive decline. Emerging evidence identifies chronic neuroinflammation as a central integrator that converts molecular pathology into synaptic failure and neurodegeneration. In this context, A\u03b2 acts as a danger-associated molecular pattern that activates microglial and astrocytic immune programs through receptors such as TREM2, TLRs, and RAGE, leading to inflammasome activation, cytokine release, and oxidative stress. These responses pathologically re-engage developmental complement pathways (C1q\u2013C3\u2013CR3), driving excessive synaptic pruning that correlates more closely with cognitive impairment than neuronal loss. Reactive astrocytes further amplify dysfunction by impairing glutamate and potassium homeostasis, promoting excitotoxic and metabolic stress, while inflammatory glia facilitate prion-like tau propagation via extracellular vesicles. Concurrent neurovascular inflammation disrupts blood\u2013brain barrier integrity and cerebral perfusion, reinforcing immune-metabolic failure. Importantly, neuroinflammatory biomarkers (GFAP, sTREM2, YKL-40, cytokines, complement, and TSPO-PET) provide dynamic readouts of disease activity and therapeutic response. Together, these findings position AD as a disorder of failed immune resolution and support precision immunomodulatory and pro-resolving therapies aimed at restoring neuroimmune homeostasis rather than merely removing protein aggregates.<\/jats:p>","DOI":"10.3390\/neurolint18020037","type":"journal-article","created":{"date-parts":[[2026,2,23]],"date-time":"2026-02-23T10:00:52Z","timestamp":1771840852000},"page":"37","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["Alzheimer\u2019s Disease as a Disorder of Neuroimmune Dysregulation"],"prefix":"10.3390","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8519-5473","authenticated-orcid":false,"given":"Gonzalo Emiliano","family":"Aranda-Abreu","sequence":"first","affiliation":[{"name":"Instituto de Investigaciones Cerebrales, Universidad Veracruzana, Xalapa 91190, Veracruz, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4497-0909","authenticated-orcid":false,"given":"Fausto","family":"Rojas-Dur\u00e1n","sequence":"additional","affiliation":[{"name":"Instituto de Investigaciones Cerebrales, Universidad Veracruzana, Xalapa 91190, Veracruz, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1617-5636","authenticated-orcid":false,"given":"Mar\u00eda Elena","family":"Hern\u00e1ndez-Aguilar","sequence":"additional","affiliation":[{"name":"Instituto de Investigaciones Cerebrales, Universidad Veracruzana, Xalapa 91190, Veracruz, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5752-4700","authenticated-orcid":false,"given":"Deissy","family":"Herrera-Covarrubias","sequence":"additional","affiliation":[{"name":"Instituto de Investigaciones Cerebrales, Universidad Veracruzana, Xalapa 91190, Veracruz, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-0029-6926","authenticated-orcid":false,"given":"Luis Roberto","family":"Tlapa-Monge","sequence":"additional","affiliation":[{"name":"Instituto de Investigaciones Cerebrales, Universidad Veracruzana, Xalapa 91190, Veracruz, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5778-0066","authenticated-orcid":false,"given":"Sonia Lilia","family":"Mestizo-Guti\u00e9rrez","sequence":"additional","affiliation":[{"name":"Facultad de Ciencias Qu\u00edmicas, Universidad Veracruzana, Xalapa 91190, Veracruz, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,2,20]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1038\/s41419-025-08186-8","article-title":"Amyloid-\u03b2 and Tau in Alzheimer\u2019s Disease: Pathogenesis, Mechanisms, and Interplay","volume":"17","author":"Abdulkhaliq","year":"2026","journal-title":"Cell Death Dis."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"7337","DOI":"10.1016\/j.cell.2025.11.033","article-title":"The Evolving Landscape of Alzheimer\u2019s Disease Therapy: From A\u03b2 to Tau","volume":"188","author":"Courade","year":"2025","journal-title":"Cell"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1007\/s13311-022-01185-z","article-title":"Heterogeneity in Alzheimer\u2019s Disease Diagnosis and Progression Rates: Implications for Therapeutic Trials","volume":"19","author":"Duara","year":"2022","journal-title":"Neurotherapeutics"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"771","DOI":"10.1016\/j.ibneur.2025.05.005","article-title":"Effect of Neuroinflammation on the Progression of Alzheimer\u2019s Disease and Its Significant Ramifications for Novel Anti-Inflammatory Treatments","volume":"18","author":"Kamila","year":"2025","journal-title":"IBRO Neurosci. Rep."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"136","DOI":"10.1111\/jnc.13607","article-title":"Neuroinflammation: The Devil is in the Details","volume":"139","author":"DiSabato","year":"2016","journal-title":"J. Neurochem."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"959","DOI":"10.1038\/s41586-025-09887-y","article-title":"Lesion-Remote Astrocytes Govern Microglia-Mediated White Matter Repair","volume":"649","author":"McCallum","year":"2025","journal-title":"Nature"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"100013","DOI":"10.1016\/j.tjpad.2024.100013","article-title":"Microglial Activation States and Their Implications for Alzheimer\u2019s Disease","volume":"12","author":"Valiukas","year":"2025","journal-title":"J. Prev. Alzheimer\u2019s Dis."},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Garc\u00eda-Dom\u00ednguez, M. (2025). Interplay Between Aging and Glial Cell Dysfunction: Implications for CNS Health. Life, 15.","DOI":"10.3390\/life15101498"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1152\/physrev.00030.2022","article-title":"Oxidative Damage in Neurodegeneration: Roles in the Pathogenesis and Progression of Alzheimer Disease","volume":"104","author":"Perluigi","year":"2024","journal-title":"Physiol. Rev."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"e1545","DOI":"10.1002\/wsbm.1545","article-title":"Complement and Microglia Dependent Synapse Elimination in Brain Development","volume":"14","author":"Soteros","year":"2022","journal-title":"WIREs Mech. Dis."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"101335","DOI":"10.1016\/j.arr.2021.101335","article-title":"Reactive Astrocytes: The Nexus of Pathological and Clinical Hallmarks of Alzheimer\u2019s Disease","volume":"68","author":"Price","year":"2021","journal-title":"Ageing Res. Rev."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"50","DOI":"10.1002\/msj.20163","article-title":"Relationship between Tau Pathology and Neuroinflammation in Alzheimer\u2019s Disease","volume":"77","author":"Metcalfe","year":"2010","journal-title":"Mt. Sinai J. Med."},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Wang, C., Zong, S., Cui, X., Wang, X., Wu, S., Wang, L., Liu, Y., and Lu, Z. (2023). The Effects of Microglia-Associated Neuroinflammation on Alzheimer\u2019s Disease. Front. Immunol., 14.","DOI":"10.3389\/fimmu.2023.1117172"},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Dias, D., and Socodato, R. (2025). Beyond Amyloid and Tau: The Critical Role of Microglia in Alzheimer\u2019s Disease Therapeutics. Biomedicines, 13.","DOI":"10.3390\/biomedicines13020279"},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Mansour, G.K., Bolgova, O., Hajjar, A.W., and Mavrych, V. (2025). Neurovascular Dysfunction and Glymphatic Impairment: An Unexplored Therapeutic Frontier in Neurodegeneration. Int. J. Mol. Sci., 26.","DOI":"10.20944\/preprints202511.0196.v1"},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Mekala, A., and Qiu, H. (2025). Interplay Between Vascular Dysfunction and Neurodegenerative Pathology: New Insights into Molecular Mechanisms and Management. Biomolecules, 15.","DOI":"10.3390\/biom15050712"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1016\/j.neuropharm.2014.10.028","article-title":"Microglial Priming and Enhanced Reactivity to Secondary Insult in Aging, and Traumatic CNS Injury, and Neurodegenerative Disease","volume":"96","author":"Norden","year":"2015","journal-title":"Neuropharmacology"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"278","DOI":"10.1159\/000548021","article-title":"Neuroinflammation across the Spectrum of Neurodegenerative Diseases: Mechanisms and Therapeutic Frontiers","volume":"32","year":"2025","journal-title":"Neuroimmunomodulation"},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"De Marchi, F., Munitic, I., Vidatic, L., Papi\u0107, E., Ra\u010dki, V., Nimac, J., Jurak, I., Novotni, G., Rogelj, B., and Vuletic, V. (2023). Overlapping Neuroimmune Mechanisms and Therapeutic Targets in Neurodegenerative Disorders. Biomedicines, 11.","DOI":"10.20944\/preprints202309.0808.v1"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"105872","DOI":"10.1016\/j.neuint.2024.105872","article-title":"Crosstalk between Peripheral Inflammation and Brain: Focus on the Responses of Microglia and Astrocytes to Peripheral Challenge","volume":"180","author":"Geloso","year":"2024","journal-title":"Neurochem. Int."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1186\/s40478-025-02203-9","article-title":"The Glymphatic System in Neurodegenerative Diseases and Brain Tumors: Mechanistic Insights, Biomarker Advances, and Therapeutic Opportunities","volume":"14","author":"Jia","year":"2025","journal-title":"Acta Neuropathol. Commun."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1177\/13872877251374353","article-title":"Neuroinflammation and Alzheimer\u2019s Disease: Unravelling the Molecular Mechanisms","volume":"108","author":"Kakkar","year":"2025","journal-title":"J. Alzheimer\u2019s Dis."},{"key":"ref_23","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_24","doi-asserted-by":"crossref","unstructured":"Ponce-Lopez, T. (2025). Peripheral Inflammation and Insulin Resistance: Their Impact on Blood-Brain Barrier Integrity and Glia Activation in Alzheimer\u2019s Disease. Int. J. Mol. Sci., 26.","DOI":"10.3390\/ijms26094209"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"100872","DOI":"10.1016\/j.jlr.2025.100872","article-title":"Lipid and Lipoprotein Metabolism in Microglia: Alzheimer\u2019s Disease Mechanisms and Interventions","volume":"66","author":"Sprenger","year":"2025","journal-title":"J. Lipid Res."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1186\/s40035-026-00541-9","article-title":"Microbiota and Alzheimer\u2019s Disease: Mechanistic Insights from a Multi-Organ Perspective","volume":"15","author":"Liao","year":"2026","journal-title":"Transl. Neurodegener."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"106877","DOI":"10.1016\/j.nbd.2025.106877","article-title":"Vascular and Glymphatic Dysfunction as Drivers of Cognitive Impairment in Alzheimer\u2019s Disease: Insights from Computational Approaches","volume":"208","author":"Fatima","year":"2025","journal-title":"Neurobiol. Dis."},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Karpuzoglu, E., Holladay, S.D., and Gogal, R.M. (2025). Inflammaging: Triggers, Molecular Mechanisms, Immunological Consequences, Sex Differences, and Cutaneous Manifestations. Front. Immunol., 16.","DOI":"10.3389\/fimmu.2025.1704203"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"457","DOI":"10.1111\/jnc.13411","article-title":"The Contribution of Neuroinflammation to Amyloid Toxicity in Alzheimer\u2019s Disease","volume":"136","author":"Minter","year":"2016","journal-title":"J. Neurochem."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"348","DOI":"10.1111\/jnc.15030","article-title":"Amyloid-\u03b2 Oligomers in Cellular Models of Alzheimer\u2019s Disease","volume":"155","author":"Fontana","year":"2020","journal-title":"J. Neurochem."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1189\/jlb.3MR0416-204R","article-title":"Danger-Associated Molecular Patterns in Alzheimer\u2019s Disease","volume":"101","author":"Venegas","year":"2017","journal-title":"J. Leucoc. Biol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"453120","DOI":"10.1155\/2008\/453120","article-title":"Microglia and Astrocyte Activation by Toll-Like Receptor Ligands: Modulation by PPAR-Gamma Agonists","volume":"2008","author":"Gurley","year":"2008","journal-title":"PPAR Res."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1016\/S0002-9440(10)64354-4","article-title":"CD36, a Class B Scavenger Receptor, Is Expressed on Microglia in Alzheimer\u2019s Disease Brains and Can Mediate Production of Reactive Oxygen Species in Response to Beta-Amyloid Fibrils","volume":"160","author":"Coraci","year":"2002","journal-title":"Am. J. Pathol."},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Cross, K., Vetter, S.W., Alam, Y., Hasan, M.Z., Nath, A.D., and Leclerc, E. (2024). Role of the Receptor for Advanced Glycation End Products (RAGE) and Its Ligands in Inflammatory Responses. Biomolecules, 14.","DOI":"10.3390\/biom14121550"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1061","DOI":"10.1016\/j.cell.2015.01.049","article-title":"TREM2 Lipid Sensing Sustains the Microglial Response in an Alzheimer\u2019s Disease Model","volume":"160","author":"Wang","year":"2015","journal-title":"Cell"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"939","DOI":"10.3233\/JAD-210268","article-title":"NLRP3 Inflammasome: A Starring Role in Amyloid-\u03b2- and Tau-Driven Pathological Events in Alzheimer\u2019s Disease","volume":"83","author":"Dias","year":"2021","journal-title":"J. Alzheimer\u2019s Dis."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"128","DOI":"10.1038\/s41419-019-1413-8","article-title":"Recent Advances in the Mechanisms of NLRP3 Inflammasome Activation and Its Inhibitors","volume":"10","author":"Yang","year":"2019","journal-title":"Cell Death Dis."},{"key":"ref_38","doi-asserted-by":"crossref","unstructured":"Yang, G., Xu, X., Gao, W., Wang, X., Zhao, Y., and Xu, Y. (2025). Microglia-Orchestrated Neuroinflammation and Synaptic Remodeling: Roles of pro-Inflammatory Cytokines and Receptors in Neurodegeneration. Front. Cell. Neurosci., 19.","DOI":"10.3389\/fncel.2025.1700692"},{"key":"ref_39","doi-asserted-by":"crossref","unstructured":"Busch, L., Eggert, S., Endres, K., and Bufe, B. (2022). The Hidden Role of Non-Canonical Amyloid \u03b2 Isoforms in Alzheimer\u2019s Disease. Cells, 11.","DOI":"10.3390\/cells11213421"},{"key":"ref_40","doi-asserted-by":"crossref","unstructured":"Wendimu, M.Y., and Hooks, S.B. (2022). Microglia Phenotypes in Aging and Neurodegenerative Diseases. Cells, 11.","DOI":"10.3390\/cells11132091"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"3129","DOI":"10.1038\/s41401-025-01576-w","article-title":"Molecular Mechanisms of Excitotoxicity and Their Relevance to the Pathogenesis of Neurodegenerative Diseases-an Update","volume":"46","author":"Wu","year":"2025","journal-title":"Acta Pharmacol. Sin."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"112196","DOI":"10.1016\/j.celrep.2023.112196","article-title":"APOE Modulates Microglial Immunometabolism in Response to Age, Amyloid Pathology, and Inflammatory Challenge","volume":"42","author":"Lee","year":"2023","journal-title":"Cell Rep."},{"key":"ref_43","doi-asserted-by":"crossref","unstructured":"Dias, D., Portugal, C.C., Relvas, J., and Socodato, R. (2025). From Genetics to Neuroinflammation: The Impact of ApoE4 on Microglial Function in Alzheimer\u2019s Disease. Cells, 14.","DOI":"10.3390\/cells14040243"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"72","DOI":"10.1186\/s13024-022-00574-4","article-title":"ApoE in Alzheimer\u2019s Disease: Pathophysiology and Therapeutic Strategies","volume":"17","author":"Raulin","year":"2022","journal-title":"Mol. Neurodegener."},{"key":"ref_45","doi-asserted-by":"crossref","unstructured":"Bojovic, D., Dagostin, A., Sullivan, S.J., Emery, B., von Gersdorff, H., and Mishra, A. (2025). Astrocyte Gap Junctions and K Channels Contribute to K+ Buffering and Regulate Neuronal Excitability. Front. Cell. Neurosci., 19.","DOI":"10.3389\/fncel.2025.1571218"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"3877","DOI":"10.1016\/j.neuron.2024.09.006","article-title":"Alzheimer\u2019s Disease-Linked Risk Alleles Elevate Microglial CGAS-Associated Senescence and Neurodegeneration in a Tauopathy Model","volume":"112","author":"Carling","year":"2024","journal-title":"Neuron"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"465","DOI":"10.1111\/jnc.13072","article-title":"APOE-Modulated A\u03b2-Induced Neuroinflammation in Alzheimer\u2019s Disease: Current Landscape, Novel Data, and Future Perspective","volume":"133","author":"Tai","year":"2015","journal-title":"J. Neurochem."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"7878","DOI":"10.15419\/s00m4g68","article-title":"Unravelling Alzheimer\u2019s Disease: Therapeutic Strategies Aimed at Neuroinflammation Signalling Pathway","volume":"12","author":"Long","year":"2025","journal-title":"Biomed. Res. Ther."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"1197","DOI":"10.1016\/j.stem.2022.07.005","article-title":"Lipid Accumulation Induced by APOE4 Impairs Microglial Surveillance of Neuronal-Network Activity","volume":"29","author":"Victor","year":"2022","journal-title":"Cell Stem Cell"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"106983","DOI":"10.1016\/j.nbd.2025.106983","article-title":"APOE4 Reshapes the Lipid Droplet Proteome and Modulates Microglial Inflammatory Responses","volume":"212","author":"Friday","year":"2025","journal-title":"Neurobiol. Dis."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"890","DOI":"10.1177\/13872877251350338","article-title":"Astrocytic Lipidopathy and Bioenergetic Failure in ApoE4-Associated Late-Onset Alzheimer\u2019s Disease: A Unifying Hypothesis","volume":"106","author":"Garrahy","year":"2025","journal-title":"J. Alzheimer\u2019s Dis."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"1735","DOI":"10.1002\/alz.12341","article-title":"Acute Systemic Inflammation Exacerbates Neuroinflammation in Alzheimer\u2019s Disease: IL-1\u03b2 Drives Amplified Responses in Primed Astrocytes and Neuronal Network Dysfunction","volume":"17","author":"Hennessy","year":"2021","journal-title":"Alzheimer\u2019s Dement."},{"key":"ref_53","doi-asserted-by":"crossref","unstructured":"Blevins, H.M., Xu, Y., Biby, S., and Zhang, S. (2022). The NLRP3 Inflammasome Pathway: A Review of Mechanisms and Inhibitors for the Treatment of Inflammatory Diseases. Front. Aging Neurosci., 14.","DOI":"10.3389\/fnagi.2022.879021"},{"key":"ref_54","doi-asserted-by":"crossref","unstructured":"Zakrzewski, P.K., and Boczek, T. (2025). Neuron-Glia Crosstalk in the Regulation of Astrocytic Antioxidative Mechanisms Following CNS Injury. Antioxidants, 14.","DOI":"10.3390\/antiox14121415"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"82","DOI":"10.1002\/agm2.12243","article-title":"Neurodegenerative Disorders: Assessing the Impact of Natural vs Drug-Induced Treatment Options","volume":"6","author":"Mathur","year":"2023","journal-title":"Aging Med."},{"key":"ref_56","doi-asserted-by":"crossref","unstructured":"M\u00fcller, L., Di Benedetto, S., and M\u00fcller, V. (2025). Neuroimmune Dynamics and Brain Aging: Mechanisms and Consequences. Front. Aging Neurosci., 17.","DOI":"10.3389\/fnagi.2025.1715045"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"837","DOI":"10.1038\/s43587-022-00281-1","article-title":"Complement C1q-Dependent Excitatory and Inhibitory Synapse Elimination by Astrocytes and Microglia in Alzheimer\u2019s Disease Mouse Models","volume":"2","author":"Dejanovic","year":"2022","journal-title":"Nat. Aging"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"247","DOI":"10.1038\/s41398-025-03458-5","article-title":"Complement C1q Is Associated with Neuroinflammation and Mediates the Association between Amyloid-\u03b2 and Tau Pathology in Alzheimer\u2019s Disease","volume":"15","author":"Guo","year":"2025","journal-title":"Transl. Psychiatry"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"135","DOI":"10.1038\/s41467-021-27702-w","article-title":"Reactive Astrocytes Acquire Neuroprotective as Well as Deleterious Signatures in Response to Tau and A\u00df Pathology","volume":"13","author":"Jiwaji","year":"2022","journal-title":"Nat. Commun."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"e70173","DOI":"10.1002\/jev2.70173","article-title":"Microglial Extracellular Vesicles Mediate C1q Deposition at the Pre-Synapse and Promote Synaptic Pruning","volume":"14","author":"Cutugno","year":"2025","journal-title":"J. Extracell. Vesicles"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"10750","DOI":"10.1093\/cercor\/bhad313","article-title":"Microglia Complement Signaling Promotes Neuronal Elimination and Normal Brain Functional Connectivity","volume":"33","author":"Deivasigamani","year":"2023","journal-title":"Cereb. Cortex"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"373","DOI":"10.2147\/ITT.S305420","article-title":"The Role of Complement in Synaptic Pruning and Neurodegeneration","volume":"10","author":"Acharya","year":"2021","journal-title":"ImmunoTargets Ther."},{"key":"ref_63","doi-asserted-by":"crossref","unstructured":"Westacott, L.J., and Wilkinson, L.S. (2022). Complement Dependent Synaptic Reorganisation During Critical Periods of Brain Development and Risk for Psychiatric Disorder. Front. Neurosci., 16.","DOI":"10.3389\/fnins.2022.840266"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"3489","DOI":"10.1007\/s00018-015-1937-8","article-title":"Glutamate Transporter EAAT2: Regulation, Function, and Potential as a Therapeutic Target for Neurological and Psychiatric Disease","volume":"72","author":"Takahashi","year":"2015","journal-title":"Cell. Mol. Life Sci."},{"key":"ref_65","doi-asserted-by":"crossref","unstructured":"Kinboshi, M., Ikeda, A., and Ohno, Y. (2020). Role of Astrocytic Inwardly Rectifying Potassium (Kir) 4.1 Channels in Epileptogenesis. Front. Neurol., 11.","DOI":"10.3389\/fneur.2020.626658"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1038\/s41583-022-00641-1","article-title":"Astrocyte Contribution to Dysfunction, Risk and Progression in Neurodegenerative Disorders","volume":"24","author":"Brandebura","year":"2023","journal-title":"Nat. Rev. Neurosci."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"965","DOI":"10.3233\/JAD-170828","article-title":"Inflammatory Cytokine, IL-1\u03b2, Regulates Glial Glutamate Transporter via MicroRNA-181a in Vitro","volume":"63","author":"Zumkehr","year":"2018","journal-title":"J. Alzheimer\u2019s Dis."},{"key":"ref_68","doi-asserted-by":"crossref","unstructured":"Fairless, R., Bading, H., and Diem, R. (2021). Pathophysiological Ionotropic Glutamate Signalling in Neuroinflammatory Disease as a Therapeutic Target. Front. Neurosci., 15.","DOI":"10.3389\/fnins.2021.741280"},{"key":"ref_69","doi-asserted-by":"crossref","unstructured":"van Putten, M.J.A.M., Fahlke, C., Kafitz, K.W., Hofmeijer, J., and Rose, C.R. (2021). Dysregulation of Astrocyte Ion Homeostasis and Its Relevance for Stroke-Induced Brain Damage. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22115679"},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"1726","DOI":"10.1093\/brain\/awae075","article-title":"Dysregulation of Extracellular Potassium Distinguishes Healthy Ageing from Neurodegeneration","volume":"147","author":"Ding","year":"2024","journal-title":"Brain"},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"1738","DOI":"10.1093\/brain\/awv081","article-title":"Reactive Microglia Drive Tau Pathology and Contribute to the Spreading of Pathological Tau in the Brain","volume":"138","author":"Maphis","year":"2015","journal-title":"Brain"},{"key":"ref_72","doi-asserted-by":"crossref","unstructured":"Perea, J.R., Llorens-Mart\u00edn, M., \u00c1vila, J., and Bol\u00f3s, M. (2018). The Role of Microglia in the Spread of Tau: Relevance for Tauopathies. Front. Cell. Neurosci., 12.","DOI":"10.3389\/fncel.2018.00172"},{"key":"ref_73","doi-asserted-by":"crossref","unstructured":"Alyenbaawi, H., Allison, W.T., and Mok, S.-A. (2020). Prion-Like Propagation Mechanisms in Tauopathies and Traumatic Brain Injury: Challenges and Prospects. Biomolecules, 10.","DOI":"10.3390\/biom10111487"},{"key":"ref_74","doi-asserted-by":"crossref","unstructured":"P\u00e9rez, M., Avila, J., and Hern\u00e1ndez, F. (2019). Propagation of Tau via Extracellular Vesicles. Front. Neurosci., 13.","DOI":"10.3389\/fnins.2019.00698"},{"key":"ref_75","doi-asserted-by":"crossref","unstructured":"Hassan, H., Rawlinson, C., Lan, Y.-L., Jenkins, S., and Chen, R. (2025). Microglia-Mediated Phagocytosis in Alzheimer\u2019s Disease: Mechanisms, Heterogeneity, and Therapeutic Insights. Biomolecules, 15.","DOI":"10.3390\/biom15111629"},{"key":"ref_76","doi-asserted-by":"crossref","unstructured":"Ogunmokun, G., Dewanjee, S., Chakraborty, P., Valupadas, C., Chaudhary, A., Kolli, V., Anand, U., Vallamkondu, J., Goel, P., and Paluru, H.P.R. (2021). The Potential Role of Cytokines and Growth Factors in the Pathogenesis of Alzheimer\u2019s Disease. Cells, 10.","DOI":"10.20944\/preprints202108.0237.v1"},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"147937","DOI":"10.1016\/j.brainres.2022.147937","article-title":"Factors Influencing the Blood-Brain Barrier Permeability","volume":"1788","author":"Zhao","year":"2022","journal-title":"Brain Res."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"e70079","DOI":"10.1111\/cns.70079","article-title":"Endothelial Dysfunctions in Blood-Brain Barrier Breakdown in Alzheimer\u2019s Disease: From Mechanisms to Potential Therapies","volume":"30","author":"Yue","year":"2024","journal-title":"CNS Neurosci. Ther."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"419","DOI":"10.1038\/nrn.2017.48","article-title":"Cerebral Blood Flow Regulation and Neurovascular Dysfunction in Alzheimer Disease","volume":"18","author":"Kisler","year":"2017","journal-title":"Nat. Rev. Neurosci."},{"key":"ref_80","first-page":"149","article-title":"Capillary Stalling: A Mechanism of Decreased Cerebral Blood Flow in AD\/ADRD","volume":"2","author":"Crumpler","year":"2021","journal-title":"J. Exp. Neurol."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/s43556-025-00400-5","article-title":"Pro-Resolving Lipid Mediators in Diseases: Exploring the Molecular Basis and Clinical Implication","volume":"7","author":"Li","year":"2026","journal-title":"Mol. Biomed."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"575","DOI":"10.1016\/j.trci.2018.06.014","article-title":"Inflammation as a Central Mechanism in Alzheimer\u2019s Disease","volume":"4","author":"Kinney","year":"2018","journal-title":"Alzheimer\u2019s Dement"},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"fcae396","DOI":"10.1093\/braincomms\/fcae396","article-title":"Glial Fibrillary Acidic Protein in Alzheimer\u2019s Disease: A Narrative Review","volume":"6","author":"Leipp","year":"2024","journal-title":"Brain Commun."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"1667","DOI":"10.1093\/brain\/awae035","article-title":"Serum GFAP Levels Correlate with Astrocyte Reactivity, Post-Mortem Brain Atrophy and Neurofibrillary Tangles","volume":"147","author":"Pastor","year":"2024","journal-title":"Brain"},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"15576","DOI":"10.1007\/s12035-025-05219-3","article-title":"The Role of Glial Fibrillary Acidic Protein in the Neuropathology of Alzheimer\u2019s Disease and Its Potential as a Blood Biomarker for Early Diagnosis and Progression","volume":"62","author":"Bandara","year":"2025","journal-title":"Mol. Neurobiol."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"903","DOI":"10.1016\/j.biopsych.2010.08.025","article-title":"YKL-40: A Novel Prognostic Fluid Biomarker for Preclinical Alzheimer\u2019s Disease","volume":"68","author":"Perrin","year":"2010","journal-title":"Biol. Psychiatry"},{"key":"ref_87","doi-asserted-by":"crossref","unstructured":"Blanco-Palmero, V.A., Rubio-Fern\u00e1ndez, M., Antequera, D., Villarejo-Galende, A., Molina, J.A., Ferrer, I., Bartolome, F., and Carro, E. (2021). Increased YKL-40 but Not C-Reactive Protein Levels in Patients with Alzheimer\u2019s Disease. Biomedicines, 9.","DOI":"10.3390\/biomedicines9091094"},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"1423","DOI":"10.2147\/NDT.S304394","article-title":"Interleukin-6 in Cerebrospinal Fluid Small Extracellular Vesicles as a Potential Biomarker for Prognosis of Aneurysmal Subarachnoid Haemorrhage","volume":"17","author":"Yao","year":"2021","journal-title":"Neuropsychiatr. Dis. Treat."},{"key":"ref_89","doi-asserted-by":"crossref","unstructured":"Tyagi, R., and Bartley, C.M. (Biol. Psychiatry, 2025). Dynamic Cytokine Relationships Across the Blood-Brain Barrier in Humans and Nonhuman Primates, Implications for Psychiatric Illness: A Systematic Review, Biol. Psychiatry, in press.","DOI":"10.1016\/j.biopsych.2025.08.022"},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"1007","DOI":"10.1002\/ana.24398","article-title":"Complement C1q-C3-Associated Synaptic Changes in Multiple Sclerosis Hippocampus","volume":"77","author":"Michailidou","year":"2015","journal-title":"Ann. Neurol."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"169","DOI":"10.1186\/s12974-023-02850-6","article-title":"Alzheimer\u2019s Disease-Associated Complement Gene Variants Influence Plasma Complement Protein Levels","volume":"20","author":"Veteleanu","year":"2023","journal-title":"J. Neuroinflamm."},{"key":"ref_92","doi-asserted-by":"crossref","unstructured":"Dupont, A.-C., Largeau, B., Santiago Ribeiro, M.J., Guilloteau, D., Tronel, C., and Arlicot, N. (2017). Translocator Protein-18 KDa (TSPO) Positron Emission Tomography (PET) Imaging and Its Clinical Impact in Neurodegenerative Diseases. Int. J. Mol. Sci., 18.","DOI":"10.3390\/ijms18040785"},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"415","DOI":"10.1016\/j.bbi.2023.07.023","article-title":"TSPO PET Brain Inflammation Imaging: A Transdiagnostic Systematic Review and Meta-Analysis of 156 Case-Control Studies","volume":"113","author":"Morrens","year":"2023","journal-title":"Brain Behav. Immun."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"113","DOI":"10.1186\/s13550-020-00699-x","article-title":"TSPO PET Detects Acute Neuroinflammation but Not Diffuse Chronically Activated MHCII Microglia in the Rat","volume":"10","author":"Qi","year":"2020","journal-title":"EJNMMI Res."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"598","DOI":"10.1136\/jnnp-2020-323951","article-title":"Cerebral Microbleeds: From Depiction to Interpretation","volume":"92","author":"Puy","year":"2021","journal-title":"J. Neurol. Neurosurg. Psychiatry"},{"key":"ref_96","doi-asserted-by":"crossref","unstructured":"Hayden, M.R. (2024). Cerebral Microbleeds Associate with Brain Endothelial Cell Activation-Dysfunction and Blood-Brain Barrier Dysfunction\/Disruption with Increased Risk of Hemorrhagic and Ischemic Stroke. Biomedicines, 12.","DOI":"10.20944\/preprints202405.0498.v1"},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"EMMM202012308","DOI":"10.15252\/emmm.202012308","article-title":"Higher CSF STREM2 and Microglia Activation Are Associated with Slower Rates of Beta-Amyloid Accumulation","volume":"12","author":"Ewers","year":"2020","journal-title":"EMBO Mol. Med."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"115218","DOI":"10.1016\/j.biopha.2023.115218","article-title":"TREM2: Potential Therapeutic Targeting of Microglia for Alzheimer\u2019s Disease","volume":"165","author":"Li","year":"2023","journal-title":"Biomed. Pharmacother."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1186\/s40035-022-00296-z","article-title":"Advances in the Development of New Biomarkers for Alzheimer\u2019s Disease","volume":"11","author":"Klyucherev","year":"2022","journal-title":"Transl. Neurodegener."},{"key":"ref_100","doi-asserted-by":"crossref","unstructured":"Inamdar, A., Bugadannavar, P., Palled, M., Umarani, S., Salve, P., Gurupadayya, B., Patil, P., and Sharma, H. (2025). Biological Determinants of Blood-Based Biomarker Levels in Alzheimer\u2019s Disease: Role of Nutrition, Inflammation, and Metabolic Factors. Front. Aging Neurosci., 17.","DOI":"10.3389\/fnagi.2025.1614962"},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"2590","DOI":"10.1038\/s41591-025-03835-z","article-title":"APOE \u03954 Carriers Share Immune-Related Proteomic Changes across Neurodegenerative Diseases","volume":"31","author":"Shvetcov","year":"2025","journal-title":"Nat. Med."},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"856","DOI":"10.1053\/j.semnuclmed.2024.09.007","article-title":"Emerging TSPO-PET Radiotracers for Imaging Neuroinflammation: A Critical Analysis","volume":"54","author":"Cumbers","year":"2024","journal-title":"Semin. Nucl. Med."},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"248","DOI":"10.1186\/s12974-025-03583-4","article-title":"TSPO Contributes to Neuropathology and Cognitive Deficits in Alzheimer\u2019s Disease","volume":"22","author":"Badina","year":"2025","journal-title":"J. Neuroinflamm."},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"100222","DOI":"10.1016\/j.dscb.2025.100222","article-title":"Neuroimaging Biomarkers: A Critical Review of Their Role in Neurological Disease Diagnosis and Management","volume":"18","author":"Wankhede","year":"2025","journal-title":"Brain Disord."},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"187","DOI":"10.1186\/s12974-024-03163-y","article-title":"Tracking Neuroinflammatory Biomarkers in Alzheimer\u2019s Disease: A Strategy for Individualized Therapeutic Approaches?","volume":"21","author":"Lista","year":"2024","journal-title":"J. Neuroinflamm."},{"key":"ref_106","doi-asserted-by":"crossref","unstructured":"Garc\u00eda-Dom\u00ednguez, M. (2025). Neuroinflammation: Mechanisms, Dual Roles, and Therapeutic Strategies in Neurological Disorders. Curr. Issues Mol. Biol., 47.","DOI":"10.3390\/cimb47060417"},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"359","DOI":"10.1038\/s41392-023-01588-0","article-title":"Microglia in Neurodegenerative Diseases: Mechanism and Potential Therapeutic Targets","volume":"8","author":"Gao","year":"2023","journal-title":"Signal Transduct. Target. Ther."},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"440","DOI":"10.1038\/s41419-020-2644-4","article-title":"Intraperitoneal Injection of IFN-\u03b3 Restores Microglial Autophagy, Promotes Amyloid-\u03b2 Clearance and Improves Cognition in APP\/PS1 Mice","volume":"11","author":"He","year":"2020","journal-title":"Cell Death Dis."},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"132","DOI":"10.2174\/187152710791012026","article-title":"Non-Steroidal Anti-Inflammatory Drugs and Alzheimer\u2019s Disease: The Epidemiological Evidence","volume":"9","author":"Szekely","year":"2010","journal-title":"CNS Neurol. Disord. Drug Targets"},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"219","DOI":"10.1016\/j.jalz.2011.03.012","article-title":"Nonsteroidal Anti-Inflammatory Drug Use and the Risk of Cognitive Impairment and Alzheimer\u2019s Disease","volume":"8","author":"Carmichael","year":"2012","journal-title":"Alzheimer\u2019s Dement."},{"key":"ref_111","doi-asserted-by":"crossref","unstructured":"Zhang, C., Wang, Y., Wang, D., Zhang, J., and Zhang, F. (2018). NSAID Exposure and Risk of Alzheimer\u2019s Disease: An Updated Meta-Analysis From Cohort Studies. Front. Aging Neurosci., 10.","DOI":"10.3389\/fnagi.2018.00083"},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"1144","DOI":"10.4103\/ni.ni_1073_22","article-title":"Role of Nonsteroidal Anti-Inflammatory Drugs as a Protective Factor in Alzheimer\u2019s Disease: A Systematic Review and Meta-Analysis","volume":"72","author":"Asthana","year":"2024","journal-title":"Neurol. India"},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"2625","DOI":"10.1007\/s11064-017-2307-8","article-title":"Microglial Interferon Signaling and White Matter","volume":"42","author":"McDonough","year":"2017","journal-title":"Neurochem. Res."},{"key":"ref_114","doi-asserted-by":"crossref","unstructured":"Tichauer, J.E., Arellano, G., Acu\u00f1a, E., Gonz\u00e1lez, L.F., Kannaiyan, N.R., Murgas, P., Panadero-Medianero, C., Iba\u00f1ez-Vega, J., Burgos, P.I., and Loda, E. (2023). Interferon-Gamma Ameliorates Experimental Autoimmune Encephalomyelitis by Inducing Homeostatic Adaptation of Microglia. Front. Immunol., 14.","DOI":"10.3389\/fimmu.2023.1191838"},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"477","DOI":"10.1007\/s00401-020-02200-3","article-title":"APOE and TREM2 Regulate Amyloid-Responsive Microglia in Alzheimer\u2019s Disease","volume":"140","author":"Nguyen","year":"2020","journal-title":"Acta Neuropathol."},{"key":"ref_116","doi-asserted-by":"crossref","unstructured":"Qin, Q., Wang, M., Yin, Y., and Tang, Y. (2022). The Specific Mechanism of TREM2 Regulation of Synaptic Clearance in Alzheimer\u2019s Disease. Front. Immunol., 13.","DOI":"10.3389\/fimmu.2022.845897"},{"key":"ref_117","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_118","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1186\/s13024-025-00922-0","article-title":"Organelle Stress in NLRP3 Inflammasome: A Central Mediator of Neurodegenerative Diseases","volume":"21","author":"Jia","year":"2026","journal-title":"Mol. Neurodegener."},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"167","DOI":"10.1016\/j.immuni.2019.12.004","article-title":"Targeted Complement Inhibition at Synapses Prevents Microglial Synaptic Engulfment and Synapse Loss in Demyelinating Disease","volume":"52","author":"Werneburg","year":"2020","journal-title":"Immunity"},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"250","DOI":"10.1038\/s41582-025-01073-y","article-title":"Knowing the Enemy: Strategic Targeting of Complement to Treat Alzheimer Disease","volume":"21","author":"Tenner","year":"2025","journal-title":"Nat. Rev. Neurol."},{"key":"ref_121","doi-asserted-by":"crossref","unstructured":"Serradas, M.L., Ding, Y., Martorell, P.V., Kuli\u0144ska, I., and Castro-Gomez, S. (2024). Therapeutic Targets in Innate Immunity to Tackle Alzheimer\u2019s Disease. Cells, 13.","DOI":"10.3390\/cells13171426"},{"key":"ref_122","doi-asserted-by":"crossref","first-page":"35","DOI":"10.3892\/ijmm.2023.5238","article-title":"Inhibitors of the NLRP3 Inflammasome Pathway as Promising Therapeutic Candidates for Inflammatory Diseases (Review)","volume":"51","author":"Zhang","year":"2023","journal-title":"Int. J. Mol. Med."},{"key":"ref_123","doi-asserted-by":"crossref","unstructured":"Garc\u00eda-Dom\u00ednguez, M. (2026). Glial Cell Dynamics in Neuroinflammation: Mechanisms, Interactions, and Therapeutic Implications. Biomedicines, 14.","DOI":"10.3390\/biomedicines14010115"},{"key":"ref_124","doi-asserted-by":"crossref","first-page":"72","DOI":"10.1186\/s12987-025-00688-z","article-title":"Restoring Brain Barriers: An Innovative Approach for Treating Neurological Disorders","volume":"22","author":"Lemarchant","year":"2025","journal-title":"Fluids Barriers CNS"},{"key":"ref_125","doi-asserted-by":"crossref","first-page":"e70057","DOI":"10.1002\/mco2.70057","article-title":"Vascular Endothelial Cell Injury: Causes, Molecular Mechanisms, and Treatments","volume":"6","author":"Xia","year":"2025","journal-title":"MedComm"},{"key":"ref_126","doi-asserted-by":"crossref","unstructured":"Venturelli, M., Pedrinolla, A., Boscolo Galazzo, I., Fonte, C., Smania, N., Tamburin, S., Muti, E., Crispoltoni, L., Stabile, A., and Pistilli, A. (2018). Impact of Nitric Oxide Bioavailability on the Progressive Cerebral and Peripheral Circulatory Impairments During Aging and Alzheimer\u2019s Disease. Front. Physiol., 9.","DOI":"10.3389\/fphys.2018.00169"},{"key":"ref_127","doi-asserted-by":"crossref","first-page":"371","DOI":"10.1111\/bpa.12152","article-title":"The Pericyte: A Forgotten Cell Type with Important Implications for Alzheimer\u2019s Disease?","volume":"24","author":"Winkler","year":"2014","journal-title":"Brain Pathol."},{"key":"ref_128","doi-asserted-by":"crossref","first-page":"507","DOI":"10.1007\/s00401-018-1893-0","article-title":"Targeting Pericytes for Therapeutic Approaches to Neurological Disorders","volume":"136","author":"Cheng","year":"2018","journal-title":"Acta Neuropathol."},{"key":"ref_129","doi-asserted-by":"crossref","unstructured":"Brown, L.S., Foster, C.G., Courtney, J.-M., King, N.E., Howells, D.W., and Sutherland, B.A. (2019). Pericytes and Neurovascular Function in the Healthy and Diseased Brain. Front. Cell. Neurosci., 13.","DOI":"10.3389\/fncel.2019.00282"},{"key":"ref_130","doi-asserted-by":"crossref","first-page":"40091","DOI":"10.31083\/JIN40091","article-title":"Mechanistic Insights and Translational Therapeutics of Neurovascular Unit Dysregulation in Vascular Cognitive Impairment","volume":"24","author":"Lin","year":"2025","journal-title":"J. Integr. Neurosci."},{"key":"ref_131","doi-asserted-by":"crossref","unstructured":"Ponce, J., Ulu, A., Hanson, C., Cameron-Smith, E., Bertoni, J., Wuebker, J., Fisher, A., Siu, K.-C., Marmelat, V., and Adamec, J. (2022). Role of Specialized Pro-Resolving Mediators in Reducing Neuroinflammation in Neurodegenerative Disorders. Front. Aging Neurosci., 14.","DOI":"10.3389\/fnagi.2022.780811"},{"key":"ref_132","doi-asserted-by":"crossref","unstructured":"Saliev, T., and Singh, P.B. (2025). Targeting Senescence: A Review of Senolytics and Senomorphics in Anti-Aging Interventions. Biomolecules, 15.","DOI":"10.3390\/biom15060860"},{"key":"ref_133","doi-asserted-by":"crossref","first-page":"261","DOI":"10.1007\/s12035-025-05504-1","article-title":"Senolytics as Modulators of Critical Signaling Pathways: A Promising Strategy to Combat Brain Aging and Neurodegenerative Disorders","volume":"63","author":"Singh","year":"2025","journal-title":"Mol. Neurobiol."},{"key":"ref_134","doi-asserted-by":"crossref","unstructured":"Saliev, T., and Singh, P.B. (2025). Senotherapeutics for Brain Aging Management. Neurol. Int., 17.","DOI":"10.3390\/neurolint17120204"},{"key":"ref_135","doi-asserted-by":"crossref","unstructured":"Bi, Y., and Ji, G. (2026). Cellular Senescence as a Therapeutic Target for Aging Intervention. Biomed. J., 100948.","DOI":"10.1016\/j.bj.2026.100948"},{"key":"ref_136","doi-asserted-by":"crossref","first-page":"138","DOI":"10.1186\/s13195-025-01783-x","article-title":"Delphinidin Attenuates Cognitive Deficits and Pathology of Alzheimer\u2019s Disease by Preventing Microglial Senescence via AMPK\/SIRT1 Pathway","volume":"17","author":"Liu","year":"2025","journal-title":"Alzheimer\u2019s Res. Ther."},{"key":"ref_137","doi-asserted-by":"crossref","first-page":"633","DOI":"10.14283\/jpad.2023.104","article-title":"Translating the Biology of Aging into New Therapeutics for Alzheimer\u2019s Disease: Senolytics","volume":"10","author":"Riessland","year":"2023","journal-title":"J. Prev. Alzheimer\u2019s Dis."},{"key":"ref_138","doi-asserted-by":"crossref","first-page":"181","DOI":"10.1016\/j.pneurobio.2009.01.001","article-title":"Inflammation in Alzheimer\u2019s Disease: Amyloid-Beta Oligomers Trigger Innate Immunity Defence via Pattern Recognition Receptors","volume":"87","author":"Salminen","year":"2009","journal-title":"Prog. Neurobiol."},{"key":"ref_139","doi-asserted-by":"crossref","first-page":"650","DOI":"10.1111\/jnc.14945","article-title":"Soluble A\u03b2 Oligomers and Protofibrils Induce NLRP3 Inflammasome Activation in Microglia","volume":"155","author":"McManus","year":"2020","journal-title":"J. Neurochem."},{"key":"ref_140","doi-asserted-by":"crossref","unstructured":"Wolfe, C.M., Fitz, N.F., Nam, K.N., Lefterov, I., and Koldamova, R. (2018). The Role of APOE and TREM2 in Alzheimer\u2019s Disease-Current Understanding and Perspectives. Int. J. Mol. Sci., 20.","DOI":"10.3390\/ijms20010081"},{"key":"ref_141","doi-asserted-by":"crossref","first-page":"102713","DOI":"10.1016\/j.arr.2025.102713","article-title":"Mitochondrial Dysfunction in Alzheimer\u2019s Disease","volume":"107","author":"Kanaan","year":"2025","journal-title":"Ageing Res. Rev."},{"key":"ref_142","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1186\/s40478-023-01590-1","article-title":"Chronic Cerebral Hypoperfusion: A Critical Feature in Unravelling the Etiology of Vascular Cognitive Impairment","volume":"11","author":"Rajeev","year":"2023","journal-title":"Acta Neuropathol. Commun."},{"key":"ref_143","doi-asserted-by":"crossref","first-page":"866","DOI":"10.1002\/ana.25600","article-title":"Amyloid, Vascular, and Resilience Pathways Associated with Cognitive Aging","volume":"86","author":"Vemuri","year":"2019","journal-title":"Ann. Neurol."},{"key":"ref_144","doi-asserted-by":"crossref","first-page":"282","DOI":"10.1007\/s12035-025-05602-0","article-title":"Toward a Unified Framework in Molecular Neurobiology of Alzheimer\u2019s Disease: Revisiting the Pathophysiological Hypotheses","volume":"63","author":"Hein","year":"2025","journal-title":"Mol. Neurobiol."},{"key":"ref_145","doi-asserted-by":"crossref","unstructured":"Brucato, F.H., and Benjamin, D.E. (2020). Synaptic Pruning in Alzheimer\u2019s Disease: Role of the Complement System. Glob. J. Med. Res., 20.","DOI":"10.34257\/GJMRFVOL20IS6PG1"},{"key":"ref_146","doi-asserted-by":"crossref","first-page":"2035","DOI":"10.1021\/acschemneuro.4c00714","article-title":"Reactive Astrocytes with Reduced Function of Glutamate Transporters in the AppNL-G-F Knock-in Mice","volume":"16","author":"Srivastava","year":"2025","journal-title":"ACS Chem. Neurosci."},{"key":"ref_147","doi-asserted-by":"crossref","first-page":"100242","DOI":"10.1016\/j.bbih.2021.100242","article-title":"The Potential Role of Glial Cells in Driving the Prion-like Transcellular Propagation of Tau in Tauopathies","volume":"14","author":"Amro","year":"2021","journal-title":"Brain Behav. Immun. Health"},{"key":"ref_148","doi-asserted-by":"crossref","unstructured":"Jiang, G., Xie, G., Li, X., and Xiong, J. (2025). Cytoskeletal Proteins and Alzheimer\u2019s Disease Pathogenesis: Focusing on the Interplay with Tau Pathology. Biomolecules, 15.","DOI":"10.3390\/biom15060831"},{"key":"ref_149","doi-asserted-by":"crossref","unstructured":"Salmina, A.B., Kharitonova, E.V., Gorina, Y.V., Teplyashina, E.A., Malinovskaya, N.A., Khilazheva, E.D., Mosyagina, A.I., Morgun, A.V., Shuvaev, A.N., and Salmin, V.V. (2021). Blood-Brain Barrier and Neurovascular Unit In Vitro Models for Studying Mitochondria-Driven Molecular Mechanisms of Neurodegeneration. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22094661"},{"key":"ref_150","doi-asserted-by":"crossref","unstructured":"Kempuraj, D., Dourvetakis, K.D., Cohen, J., Valladares, D.S., Joshi, R.S., Kothuru, S.P., Anderson, T., Chinnappan, B., Cheema, A.K., and Klimas, N.G. (2024). Neurovascular Unit, Neuroinflammation and Neurodegeneration Markers in Brain Disorders. Front. Cell. Neurosci., 18.","DOI":"10.3389\/fncel.2024.1491952"},{"key":"ref_151","doi-asserted-by":"crossref","unstructured":"Roveta, F., Bonino, L., Piella, E.M., Rainero, I., and Rubino, E. (2024). Neuroinflammatory Biomarkers in Alzheimer\u2019s Disease: From Pathophysiology to Clinical Implications. Int. J. Mol. Sci., 25.","DOI":"10.3390\/ijms252211941"},{"key":"ref_152","doi-asserted-by":"crossref","first-page":"116884","DOI":"10.1016\/j.biopha.2024.116884","article-title":"Estimating the Therapeutic Potential of NSAIDs and Linoleic Acid-Isomers Supplementation against Neuroinflammation","volume":"177","author":"Vieira","year":"2024","journal-title":"Biomed. Pharmacother."},{"key":"ref_153","doi-asserted-by":"crossref","first-page":"967","DOI":"10.1080\/14728222.2019.1691525","article-title":"Inflammation Resolution and Specialized Pro-Resolving Lipid Mediators in CNS Diseases","volume":"23","author":"Shang","year":"2019","journal-title":"Expert Opin. Ther. Targets"},{"key":"ref_154","doi-asserted-by":"crossref","first-page":"20862","DOI":"10.18632\/aging.104104","article-title":"TREM2 Ameliorates Neuroinflammatory Response and Cognitive Impairment via PI3K\/AKT\/FoxO3a Signaling Pathway in Alzheimer\u2019s Disease Mice","volume":"12","author":"Wang","year":"2020","journal-title":"Aging"}],"container-title":["Neurology International"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2035-8377\/18\/2\/37\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,2,25]],"date-time":"2026-02-25T10:20:38Z","timestamp":1772014838000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2035-8377\/18\/2\/37"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,2,20]]},"references-count":154,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2026,2]]}},"alternative-id":["neurolint18020037"],"URL":"https:\/\/doi.org\/10.3390\/neurolint18020037","relation":{},"ISSN":["2035-8377"],"issn-type":[{"value":"2035-8377","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,2,20]]}}}