{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,3]],"date-time":"2026-10-03T03:46:42Z","timestamp":1790999202313,"version":"4.1.0"},"reference-count":197,"publisher":"MDPI AG","issue":"13","license":[{"start":{"date-parts":[[2025,6,27]],"date-time":"2025-06-27T00:00:00Z","timestamp":1750982400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Alzheimer\u2019s disease (AD) and schizophrenia are traditionally considered distinct clinical entities, yet growing evidence highlights substantial overlap in their molecular and neuroinflammatory pathogenesis. This review explores current insights into the shared and divergent mechanisms underlying these disorders, with emphasis on neuroinflammation, autophagy dysfunction, blood\u2013brain barrier (BBB) disruption, and cognitive impairment. We examine key signaling pathways, particularly spleen tyrosine kinase (SYK), the mechanistic (or mammalian) target of rapamycin (mTOR), and the S100 calcium-binding protein B (S100B)\/receptor for advanced glycation end-products (RAGE) axis, that link glial activation, excitatory\/inhibitory neurotransmitter imbalances, and impaired proteostasis across both disorders. Specific biomarkers such as S100B, matrix metalloproteinase 9 (MMP9), and soluble RAGE show promise for stratifying disease subtypes and predicting treatment response. Moreover, psychiatric symptoms frequently precede cognitive decline in both AD and schizophrenia, suggesting that mood and behavioral disturbances may serve as early diagnostic indicators. The roles of autophagic failure, cellular senescence, and impaired glymphatic clearance are also explored as contributors to chronic inflammation and neurodegeneration. Current treatments, including cholinesterase inhibitors and antipsychotics, primarily offer symptomatic relief, while emerging therapeutic approaches target upstream molecular drivers, such as mTOR inhibition and RAGE antagonism. Finally, we discuss the future potential of personalized medicine guided by genetic, neuroimaging, and biomarker profiles to optimize diagnosis and treatment strategies in both AD and schizophrenia. A greater understanding of the pathophysiological convergence between these disorders may pave the way for cross-diagnostic interventions and improved clinical outcomes.<\/jats:p>","DOI":"10.3390\/ijms26136237","type":"journal-article","created":{"date-parts":[[2025,7,1]],"date-time":"2025-07-01T05:28:28Z","timestamp":1751347708000},"page":"6237","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["The Inflammatory Nexus: Unraveling Shared Pathways and Promising Treatments in Alzheimer\u2019s Disease and Schizophrenia"],"prefix":"10.3390","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0009-0003-7672-2798","authenticated-orcid":false,"given":"Aurelio Pio","family":"Russo","sequence":"first","affiliation":[{"name":"Department of Anatomy and Embryology, George Emil Palade University of Medicine, Pharmacy, Science, and Technology of T\u00e2rgu Mure\u015f, 540139 T\u00e2rgu Mure\u015f, Romania"},{"name":"Doctoral School of Medicine and Pharmacy, George Emil Palade University of Medicine, Pharmacy, Science, and Technology of T\u00e2rgu Mure\u015f, 540139 T\u00e2rgu Mure\u015f, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-3833-0184","authenticated-orcid":false,"given":"Ylenia","family":"Pastorello","sequence":"additional","affiliation":[{"name":"Department of Anatomy and Embryology, George Emil Palade University of Medicine, Pharmacy, Science, and Technology of T\u00e2rgu Mure\u015f, 540139 T\u00e2rgu Mure\u015f, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-8319-8134","authenticated-orcid":false,"given":"L\u00f3r\u00e1nd","family":"D\u00e9nes","sequence":"additional","affiliation":[{"name":"Department of Anatomy and Embryology, George Emil Palade University of Medicine, Pharmacy, Science, and Technology of T\u00e2rgu Mure\u015f, 540139 T\u00e2rgu Mure\u015f, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Klara","family":"Br\u00eenzaniuc","sequence":"additional","affiliation":[{"name":"Department of Anatomy and Embryology, George Emil Palade University of Medicine, Pharmacy, Science, and Technology of T\u00e2rgu Mure\u015f, 540139 T\u00e2rgu Mure\u015f, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jerzy","family":"Krupinski","sequence":"additional","affiliation":[{"name":"Department of Neurology, M\u00fatuaTerrassa University Hospital, 08221 Barcelona, Spain"},{"name":"Department of Life Sciences, Manchester Metropolitan University, Manchester M1 5GD, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3767-4861","authenticated-orcid":false,"given":"Mark","family":"Slevin","sequence":"additional","affiliation":[{"name":"Centre for Advanced Medical and Pharmaceutical Research, George Emil Palade University of Medicine, Pharmacy, Science, and Technology of T\u00e2rgu Mure\u015f, 540139 T\u00e2rgu Mure\u015f, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,6,27]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Giri, P.M., Banerjee, A., Ghosal, A., and Layek, B. (2024). Neuroinflammation in Neurodegenerative Disorders: Current Knowledge and Therapeutic Implications. Int. J. Mol. Sci., 25.","DOI":"10.3390\/ijms25073995"},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Lamptey, R.N.L., Chaulagain, B., Trivedi, R., Gothwal, A., Layek, B., and Singh, J. (2022). A Review of the Common Neurodegenerative Disorders: Current Therapeutic Approaches and the Potential Role of Nanotherapeutics. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms23031851"},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Muddapu, V.R., Dharshini, S.A.P., Chakravarthy, V.S., and Gromiha, M.M. (2020). Neurodegenerative Diseases\u2014Is Metabolic Deficiency the Root Cause?. Front. Neurosci., 14.","DOI":"10.3389\/fnins.2020.00213"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"263","DOI":"10.1016\/j.ncl.2017.01.005","article-title":"Early-Onset Alzheimer Disease","volume":"35","author":"Mendez","year":"2017","journal-title":"Neurol. Clin."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"222","DOI":"10.1016\/S1474-4422(20)30440-3","article-title":"New insights into atypical Alzheimer\u2019s disease in the era of biomarkers","volume":"20","author":"Yong","year":"2021","journal-title":"Lancet Neurol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"207","DOI":"10.1016\/j.jare.2021.07.001","article-title":"CRISPR\/Cas9 gene editing: New hope for Alzheimer\u2019s disease therapeutics","volume":"40","author":"Bhardwaj","year":"2022","journal-title":"J. Adv. Res."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"267","DOI":"10.1038\/s41392-023-01486-5","article-title":"Role of neuroinflammation in neurodegeneration development","volume":"8","author":"Zhang","year":"2023","journal-title":"Signal Transduct. Target. Ther."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"195","DOI":"10.1016\/j.jalz.2015.05.017","article-title":"Neuropsychiatric symptoms as early manifestations of emergent dementia: Provisional diagnostic criteria for mild behavioral impairment","volume":"12","author":"Ismail","year":"2016","journal-title":"Alzheimer\u2019s Dement."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"773","DOI":"10.3233\/JAD-170786","article-title":"Medical Comorbidity in Alzheimer\u2019s Disease: A Nested Case-Control Study","volume":"63","author":"Wang","year":"2018","journal-title":"J. Alzheimer\u2019s Dis."},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Santiago, J.A., and Potashkin, J.A. (2021). The Impact of Disease Comorbidities in Alzheimer\u2019s Disease. Front. Aging Neurosci., 13.","DOI":"10.3389\/fnagi.2021.631770"},{"key":"ref_11","first-page":"e12593","article-title":"Exploring the link between comorbidities and Alzheimer\u2019s dementia in the Australian Imaging, Biomarker & Lifestyle (AIBL) study","volume":"16","author":"Nguyen","year":"2024","journal-title":"Alzheimer\u2019s Dement. Diagn. Assess. Dis. Monit."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"2047","DOI":"10.2147\/NDT.S172933","article-title":"Schizophrenia and risk of dementia: A meta-analysis study","volume":"14","author":"Cai","year":"2018","journal-title":"Neuropsychiatr. Dis. Treat."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1461","DOI":"10.1590\/0001-3765201520140716","article-title":"Alzheimer\u2019s disease associated with psychiatric comorbidities","volume":"87","author":"Garcez","year":"2015","journal-title":"An. Acad. Bras. Cienc."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"315","DOI":"10.1016\/B978-0-444-64123-6.00022-9","article-title":"Schizophrenia spectrum and other psychotic disorders","volume":"175","author":"Lewine","year":"2020","journal-title":"Handb. Clin. Neurol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1016\/j.euroneuro.2024.02.005","article-title":"Identification and treatment of individuals with childhood-onset and early-onset schizophrenia","volume":"82","author":"Correll","year":"2024","journal-title":"Eur. Neuropsychopharmacol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1016\/j.schres.2013.05.028","article-title":"Definition and description of schizophrenia in the DSM-5","volume":"150","author":"Tandon","year":"2013","journal-title":"Schizophr. Res."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"367","DOI":"10.1016\/j.jad.2024.09.015","article-title":"Association of early- and late-life bipolar disorder with incident dementia. A Danish cohort study","volume":"367","author":"Nielsen","year":"2024","journal-title":"J. Affect. Disord."},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Liu, R.M. (2022). Aging, Cellular Senescence, and Alzheimer\u2019s Disease. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms23041989"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1095","DOI":"10.1001\/jamapsychiatry.2015.1546","article-title":"Long-term risk of dementia in persons with schizophrenia: A danish population-based cohort study","volume":"72","author":"Ribe","year":"2015","journal-title":"JAMA Psychiatry"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"e065861","DOI":"10.1002\/alz.065861","article-title":"Genetic Relationship between Alzheimer\u2019s Disease and Schizophrenia","volume":"18","author":"Chen","year":"2022","journal-title":"Alzheimer\u2019s Dement."},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Calero, M., G\u00f3mez-Ramos, A., Calero, O., Soriano, E., Avila, J., and Medina, M. (2015). Additional mechanisms conferring genetic susceptibility to Alzheimer\u2019s disease. Front. Cell. Neurosci., 9.","DOI":"10.3389\/fncel.2015.00138"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1316","DOI":"10.1038\/mp.2011.125","article-title":"Genome-wide association study of Alzheimer\u2019s disease with psychotic symptoms","volume":"17","author":"Hollingworth","year":"2012","journal-title":"Mol. Psychiatry"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"183","DOI":"10.1007\/s12264-016-0011-3","article-title":"An Overview of Genome-Wide Association Studies in Alzheimer\u2019s Disease","volume":"32","author":"Shen","year":"2016","journal-title":"Neurosci. Bull."},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Shokrgozar, A., Rahimi, M., and Shoraka, S. (2025). Identification of key genes and pathways in schizophrenia: A bioinformatics analysis based on GWAS and GEO. Front. Psychiatry, 16.","DOI":"10.3389\/fpsyt.2025.1464676"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"56","DOI":"10.1038\/s41398-019-0398-5","article-title":"Comprehensive functional annotation of susceptibility SNPs prioritized 10 genes for schizophrenia","volume":"9","author":"Niu","year":"2019","journal-title":"Transl. Psychiatry"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"150","DOI":"10.1038\/s41398-025-03348-w","article-title":"Identification of genetic architecture shared between schizophrenia and Alzheimer\u2019s disease","volume":"15","author":"Liu","year":"2025","journal-title":"Transl. Psychiatry"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"fcaf112","DOI":"10.1093\/braincomms\/fcaf112","article-title":"Examining the genetic relationship between Alzheimer\u2019s disease, schizophrenia and their shared risk factors using genomic structural equation modelling","volume":"7","author":"Sousa","year":"2025","journal-title":"Brain Commun."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"168","DOI":"10.1159\/000381523","article-title":"Anticholinergic Activity and Schizophrenia","volume":"15","author":"Tani","year":"2015","journal-title":"Neurodegener. Dis."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"101","DOI":"10.2174\/1570159X13666150716165726","article-title":"Alzheimer\u2019s Disease: Targeting the Cholinergic System","volume":"14","author":"Guimaraes","year":"2016","journal-title":"Curr. Neuropharmacol."},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Chen, Z.R., Huang, J.B., Yang, S.L., and Hong, F.F. (2022). Role of Cholinergic Signaling in Alzheimer\u2019s Disease. Molecules, 27.","DOI":"10.3390\/molecules27061816"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"2320","DOI":"10.1038\/s41386-021-01070-x","article-title":"Lower cholinergic basal forebrain volumes link with cognitive difficulties in schizophrenia","volume":"46","author":"Avram","year":"2021","journal-title":"Neuropsychopharmacology"},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Eickhoff, S., Franzen, L., Korda, A., Rogg, H., Trulley, V.-N., Borgwardt, S., and Avram, M. (2022). The Basal Forebrain Cholinergic Nuclei and Their Relevance to Schizophrenia and Other Psychotic Disorders. Front. Psychiatry, 13.","DOI":"10.3389\/fpsyt.2022.909961"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1145","DOI":"10.2147\/NDT.S406371","article-title":"Xanomeline-Trospium and Muscarinic Involvement in Schizophrenia","volume":"19","author":"Kidambi","year":"2023","journal-title":"Neuropsychiatr. Dis. Treat."},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Lee, E.E., Winston-Gray, C., Barlow, J.W., Rissman, R.A., and Jeste, D.V. (2021). Plasma Levels of Neuron- and Astrocyte-Derived Exosomal Amyloid Beta1-42, Amyloid Beta1-40, and Phosphorylated Tau Levels in Schizophrenia Patients and Non-psychiatric Comparison Subjects: Relationships with Cognitive Functioning and Psychopathology. Front. Psychiatry, 11.","DOI":"10.3389\/fpsyt.2020.532624"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"17","DOI":"10.2217\/fnl.10.61","article-title":"Alzheimers disease and schizophrenia: Evidence of a specific, shared molecular background","volume":"6","author":"Prestia","year":"2011","journal-title":"Future Neurol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"1284","DOI":"10.1038\/s41380-022-01924-w","article-title":"Inflammation and cognition in severe mental illness: Patterns of covariation and subgroups","volume":"28","author":"Ueland","year":"2023","journal-title":"Mol. Psychiatry"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"388","DOI":"10.1016\/S1474-4422(15)70016-5","article-title":"Neuroinflammation in Alzheimer\u2019s disease","volume":"14","author":"Heneka","year":"2015","journal-title":"Lancet Neurol."},{"key":"ref_38","doi-asserted-by":"crossref","unstructured":"Vall\u00e9e, A. (2022). Neuroinflammation in Schizophrenia: The Key Role of the WNT\/\u03b2-Catenin Pathway. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms23052810"},{"key":"ref_39","doi-asserted-by":"crossref","unstructured":"Beaurain, M., Salabert, A.S., Payoux, P., Gras, E., and Talmont, F. (2024). NMDA Receptors: Distribution, Role, and Insights into Neuropsychiatric Disorders. Pharmaceuticals, 17.","DOI":"10.3390\/ph17101265"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"351","DOI":"10.1016\/bs.apha.2016.01.006","article-title":"The NMDA Receptor and Schizophrenia. From Pathophysiology to Treatment","volume":"76","author":"Balu","year":"2016","journal-title":"Adv. Pharmacol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"1041","DOI":"10.3233\/JAD-160763","article-title":"Role of Glutamate and NMDA Receptors in Alzheimer\u2019s Disease","volume":"57","author":"Wang","year":"2017","journal-title":"J. Alzheimer\u2019s Dis."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"e1200","DOI":"10.1002\/ctm2.1200","article-title":"The microglial immunoreceptor tyrosine-based motif-Syk signaling pathway is a promising target of immunotherapy for Alzheimer\u2019s disease","volume":"13","author":"Wang","year":"2023","journal-title":"Clin. Transl. Med."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"4135","DOI":"10.1016\/j.cell.2022.09.030","article-title":"SYK coordinates neuroprotective microglial responses in neurodegenerative disease","volume":"185","author":"Ennerfelt","year":"2022","journal-title":"Cell"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"849","DOI":"10.17219\/acem\/68846","article-title":"CXCL9, CXCL10, CXCL11, and their receptor (CXCR3) in neuroinflammation and neurodegeneration","volume":"27","author":"Koper","year":"2018","journal-title":"Adv. Clin. Exp. Med."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"44","DOI":"10.1186\/s13024-021-00428-5","article-title":"Mammalian\/mechanistic target of rapamycin (mTOR) complexes in neurodegeneration","volume":"16","author":"Querfurth","year":"2021","journal-title":"Mol. Neurodegener."},{"key":"ref_46","doi-asserted-by":"crossref","unstructured":"Chen, L., Saito, R., Noda-Narita, S., Kassai, H., and Aiba, A. (2024). Hyperactive mTORC1 in striatum dysregulates dopamine receptor expression and odor preference behavior. Front. Neurosci., 18.","DOI":"10.3389\/fnins.2024.1461178"},{"key":"ref_47","doi-asserted-by":"crossref","unstructured":"Deleyto-Seldas, N., and Efeyan, A. (2021). The mTOR\u2013Autophagy Axis and the Control of Metabolism. Front. Cell Dev. Biol., 9.","DOI":"10.3389\/fcell.2021.655731"},{"key":"ref_48","doi-asserted-by":"crossref","unstructured":"Ryskalin, L., Limanaqi, F., Frati, A., Busceti, C.L., and Fornai, F. (2018). mTOR-related brain dysfunctions in neuropsychiatric disorders. Int. J. Mol. Sci., 19.","DOI":"10.3390\/ijms19082226"},{"key":"ref_49","doi-asserted-by":"crossref","unstructured":"Ibarra-Lecue, I., Diez-Alarcia, R., Morentin, B., Meana, J.J., Callado, L.F., and Urig\u00fcen, L. (2020). Ribosomal Protein S6 Hypofunction in Postmortem Human Brain Links mTORC1-Dependent Signaling and Schizophrenia. Front. Pharmacol., 11.","DOI":"10.3389\/fphar.2020.00344"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"pyae010","DOI":"10.1093\/ijnp\/pyae010","article-title":"PI3K-AKT\/mTOR Signaling in Psychiatric Disorders: A Valuable Target to Stimulate or Suppress?","volume":"27","author":"Chen","year":"2024","journal-title":"Int. J. Neuropsychopharmacol."},{"key":"ref_51","doi-asserted-by":"crossref","unstructured":"Kciuk, M., Kruczkowska, W., Ga\u0142\u0119ziewska, J., Wanke, K., Ka\u0142uzi\u0144ska-Ko\u0142at, \u017b., Aleksandrowicz, M., and Kontek, R. (2024). Alzheimer\u2019s Disease as Type 3 Diabetes: Understanding the Link and Implications. Int. J. Mol. Sci., 25.","DOI":"10.3390\/ijms252211955"},{"key":"ref_52","doi-asserted-by":"crossref","unstructured":"Nguyen, T.T., Ta, Q.T.H., Nguyen, T.K.O., Nguyen, T.T.D., and Giau, V. (2020). Van Type 3 diabetes and its role implications in Alzheimer\u2019s disease. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21093165"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"509","DOI":"10.1515\/revneuro-2013-0050","article-title":"Insulin resistance, neuroinflammation, and Alzheimer\u2019s disease","volume":"25","author":"Najem","year":"2014","journal-title":"Rev. Neurosci."},{"key":"ref_54","doi-asserted-by":"crossref","unstructured":"S\u0119dzikowska, A., and Szablewski, L. (2021). Insulin and Insulin Resistance in Alzheimer\u2019s Disease. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22189987"},{"key":"ref_55","doi-asserted-by":"crossref","unstructured":"Kong, Y., Wang, F., Wang, J., Liu, C., Zhou, Y., Xu, Z., Zhang, C., Sun, B., and Guan, Y. (2020). Pathological Mechanisms Linking Diabetes Mellitus and Alzheimer\u2019s Disease: The Receptor for Advanced Glycation End Products (RAGE). Front. Aging Neurosci., 12.","DOI":"10.3389\/fnagi.2020.00217"},{"key":"ref_56","doi-asserted-by":"crossref","unstructured":"Wei, Z., Koya, J., and Reznik, S.E. (2021). Insulin Resistance Exacerbates Alzheimer Disease via Multiple Mechanisms. Front. Neurosci., 15.","DOI":"10.3389\/fnins.2021.687157"},{"key":"ref_57","doi-asserted-by":"crossref","unstructured":"Datta, S., Rahman, M.A., Koka, S., and Boini, K.M. (2024). High Mobility Group Box 1 (HMGB1): Molecular Signaling and Potential Therapeutic Strategies. Cells, 13.","DOI":"10.3390\/cells13231946"},{"key":"ref_58","doi-asserted-by":"crossref","unstructured":"Rojas, A., Lindner, C., Schneider, I., Gonzalez, I., and Uribarri, J. (2024). The RAGE Axis: A Relevant Inflammatory Hub in Human Diseases. Biomolecules, 14.","DOI":"10.3390\/biom14040412"},{"key":"ref_59","doi-asserted-by":"crossref","unstructured":"Pluta, R., Kocki, J., Bogucki, J., Bogucka-Kocka, A., and Czuczwar, S.J. (2023). LRP1 and RAGE Genes Transporting Amyloid and Tau Protein in the Hippocampal CA3 Area in an Ischemic Model of Alzheimer\u2019s Disease with 2-Year Survival. Cells, 12.","DOI":"10.3390\/cells12232763"},{"key":"ref_60","first-page":"421","article-title":"The Receptor for Advanced Glycation Endproducts (RAGE) and Mediation of Inflammatory Neurodegeneration","volume":"8","author":"Derk","year":"2018","journal-title":"J. Alzheimers Dis. Park."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"133","DOI":"10.1038\/nrneurol.2017.188","article-title":"Blood-brain barrier breakdown in Alzheimer disease and other neurodegenerative disorders","volume":"14","author":"Sweeney","year":"2018","journal-title":"Nat. Rev. Neurol."},{"key":"ref_62","doi-asserted-by":"crossref","unstructured":"Reddy, V.P., Aryal, P., and Soni, P. (2023). RAGE Inhibitors in Neurodegenerative Diseases. Biomedicines, 11.","DOI":"10.3390\/biomedicines11041131"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"2889","DOI":"10.1038\/s41380-019-0393-5","article-title":"MMP9\/RAGE pathway overactivation mediates redox dysregulation and neuroinflammation, leading to inhibitory\/excitatory imbalance: A reverse translation study in schizophrenia patients","volume":"25","author":"Dwir","year":"2020","journal-title":"Mol. Psychiatry"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1038\/s41537-024-00494-w","article-title":"Elevated plasma matrix metalloproteinase 9 in schizophrenia patients associated with poor antipsychotic treatment response and white matter density deficits","volume":"10","author":"Li","year":"2024","journal-title":"Schizophrenia"},{"key":"ref_65","doi-asserted-by":"crossref","unstructured":"Di Benedetto, G., Burgaletto, C., Bellanca, C.M., Munaf\u00f2, A., Bernardini, R., and Cantarella, G. (2022). Role of Microglia and Astrocytes in Alzheimer\u2019s Disease: From Neuroinflammation to Ca2+ Homeostasis Dysregulation. Cells, 11.","DOI":"10.3390\/cells11172728"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"206","DOI":"10.1186\/s12974-022-02565-0","article-title":"Astrocytic and microglial cells as the modulators of neuroinflammation in Alzheimer\u2019s disease","volume":"19","author":"Singh","year":"2022","journal-title":"J. Neuroinflamm."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"1057","DOI":"10.1007\/s40263-017-0483-3","article-title":"Targeting Neuroinflammation to Treat Alzheimer\u2019s Disease","volume":"31","author":"Boddeke","year":"2017","journal-title":"CNS Drugs"},{"key":"ref_68","doi-asserted-by":"crossref","unstructured":"Lee, E., and Chang, Y. (2025). Modulating Neuroinflammation as a Prospective Therapeutic Target in Alzheimer\u2019s Disease. Cells, 14.","DOI":"10.3390\/cells14030168"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"113101","DOI":"10.1016\/j.bbr.2020.113101","article-title":"Roles of inflammation in intrinsic pathophysiology and antipsychotic drug-induced metabolic disturbances of schizophrenia","volume":"402","author":"Prestwood","year":"2021","journal-title":"Behav. Brain Res."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"3779","DOI":"10.1038\/s41380-024-02614-5","article-title":"Modulation of neuroinflammation and oxidative stress by targeting GPR55\u2014New approaches in the treatment of psychiatric disorders","volume":"29","author":"Apweiler","year":"2024","journal-title":"Mol. Psychiatry"},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"60","DOI":"10.1186\/s12987-024-00557-1","article-title":"Cellular and molecular mechanisms of the blood\u2013brain barrier dysfunction in neurodegenerative diseases","volume":"21","author":"Chen","year":"2024","journal-title":"Fluids Barriers CNS"},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"6564585","DOI":"10.1155\/2021\/6564585","article-title":"Blood-Brain Barrier Overview: Structural and Functional Correlation","volume":"2021","author":"Alahmari","year":"2021","journal-title":"Neural Plast."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"2659","DOI":"10.1038\/s41380-022-01511-z","article-title":"The blood-brain barrier in aging and neurodegeneration","volume":"27","author":"Knox","year":"2022","journal-title":"Mol. Psychiatry"},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"34","DOI":"10.1016\/j.jconrel.2022.05.042","article-title":"Focused ultrasound\/microbubbles-assisted BBB opening enhances LNP-mediated mRNA delivery to brain","volume":"348","author":"Ogawa","year":"2022","journal-title":"J. Control. Release"},{"key":"ref_75","doi-asserted-by":"crossref","unstructured":"Du, H., Meng, X., Yao, Y., and Xu, J. (2022). The mechanism and efficacy of GLP-1 receptor agonists in the treatment of Alzheimer\u2019s disease. Front. Endocrinol., 13.","DOI":"10.3389\/fendo.2022.1033479"},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"777","DOI":"10.3233\/ADR-230181","article-title":"Clinical Evidence for GLP-1 Receptor Agonists in Alzheimer\u2019s Disease: A Systematic Review","volume":"8","author":"Liang","year":"2024","journal-title":"J. Alzheimers Dis. Rep."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"106550","DOI":"10.1016\/j.phrs.2022.106550","article-title":"Glucagon-like peptide-1 (GLP-1) receptor agonists and neuroinflammation: Implications for neurodegenerative disease treatment","volume":"186","author":"Kopp","year":"2022","journal-title":"Pharmacol. Res."},{"key":"ref_78","doi-asserted-by":"crossref","unstructured":"Zhang, F., Zhang, J., Wang, X., Han, M., Fei, Y., and Wang, J. (2025). Blood\u2013Brain Barrier Disruption in Schizophrenia: Insights, Mechanisms, and Future Directions. Int. J. Mol. Sci., 26.","DOI":"10.3390\/ijms26030873"},{"key":"ref_79","doi-asserted-by":"crossref","unstructured":"Moussiopoulou, J., Yakimov, V., Rauchmann, B.-S., Toth, H., Melcher, J., J\u00e4ger, I., Lutz, I., Kallweit, M., Papazov, B., and Seelos, K. (2023). Increased blood\u2013brain barrier leakage in schizophrenia spectrum disorders compared to healthy controls in dynamic contrast-enhanced magnetic resonance imaging. medRxiv.","DOI":"10.1101\/2023.12.12.23299782"},{"key":"ref_80","first-page":"e60682","article-title":"Brain Vascular Expression of Monomeric C-Reactive Protein Is Blocked by C10M Following Intraperitoneal Injection in an ApoE\u2212\/\u2212 Murine Model of Dyslipidemia: An Immunohistochemical Analysis","volume":"16","author":"Pastorello","year":"2024","journal-title":"Cureus"},{"key":"ref_81","doi-asserted-by":"crossref","unstructured":"Eshraghi, M., Adlimoghaddam, A., Mahmoodzadeh, A., Sharifzad, F., Yasavoli-Sharahi, H., Lorzadeh, S., Albensi, B.C., and Ghavami, S. (2021). Alzheimer\u2019s disease pathogenesis: Role of autophagy and mitophagy focusing in microglia. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22073330"},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"1019","DOI":"10.1016\/j.apsb.2022.01.008","article-title":"Impairment of the autophagy\u2013lysosomal pathway in Alzheimer\u2019s diseases: Pathogenic mechanisms and therapeutic potential","volume":"12","author":"Zhang","year":"2022","journal-title":"Acta Pharm. Sin. B"},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"177469","DOI":"10.1016\/j.ejphar.2025.177469","article-title":"Unraveling the potential of neuroinflammation and autophagy in schizophrenia","volume":"997","author":"Tao","year":"2025","journal-title":"Eur. J. Pharmacol."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"126","DOI":"10.1038\/mp.2013.174","article-title":"Autophagy has a key role in the pathophysiology of schizophrenia","volume":"20","author":"Malishkevich","year":"2015","journal-title":"Mol. Psychiatry"},{"key":"ref_85","doi-asserted-by":"crossref","unstructured":"Schneider, J.L., Miller, A.M., and Woesner, M.E. (2017). Autophagy and Schizophrenia: A Closer Look at How Dysregulation of Neuronal Cell Homeostasis Influences the Pathogenesis of Schizophrenia. Einstein J. Biol. Med., 31.","DOI":"10.23861\/EJBM201631752"},{"key":"ref_86","doi-asserted-by":"crossref","unstructured":"Rocchi, A., Yamamoto, S., Ting, T., Fan, Y., Sadleir, K., Wang, Y., Zhang, W., Huang, S., Levine, B., and Vassar, R. (2017). A Becn1 mutation mediates hyperactive autophagic sequestration of amyloid oligomers and improved cognition in Alzheimer\u2019s disease. PLoS Genet., 13.","DOI":"10.1371\/journal.pgen.1006962"},{"key":"ref_87","doi-asserted-by":"crossref","unstructured":"Barmaki, H., Nourazarian, A., and Khaki-Khatibi, F. (2023). Proteostasis and neurodegeneration: A closer look at autophagy in Alzheimer\u2019s disease. Front. Aging Neurosci., 15.","DOI":"10.3389\/fnagi.2023.1281338"},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"714","DOI":"10.1016\/j.tins.2021.06.007","article-title":"Cellular senescence at the crossroads of inflammation and Alzheimer\u2019s disease","volume":"44","author":"Guerrero","year":"2021","journal-title":"Trends Neurosci."},{"key":"ref_89","doi-asserted-by":"crossref","unstructured":"Hendrickx, J.O., Martinet, W., Van Dam, D., and De Meyer, G.R.Y. (2021). Inflammation, Nitro-Oxidative Stress, Impaired Autophagy, and Insulin Resistance as a Mechanistic Convergence Between Arterial Stiffness and Alzheimer\u2019s Disease. Front. Mol. Biosci., 8.","DOI":"10.3389\/fmolb.2021.651215"},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1038\/nrn2967","article-title":"Amyloid-\u03b2 and tau\u2014A toxic pas de deux in Alzheimer\u2019s disease","volume":"12","author":"Ittner","year":"2011","journal-title":"Nat. Rev. Neurosci."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1016\/j.schres.2014.06.021","article-title":"Redox dysregulation, neuroinflammation, and NMDA receptor hypofunction: A \u201ccentral hub\u201d in schizophrenia pathophysiology?","volume":"176","author":"Steullet","year":"2016","journal-title":"Schizophr. Res."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"936","DOI":"10.1038\/mp.2017.47","article-title":"Oxidative stress-driven parvalbumin interneuron impairment as a common mechanism in models of schizophrenia","volume":"22","author":"Steullet","year":"2017","journal-title":"Mol. Psychiatry"},{"key":"ref_93","doi-asserted-by":"crossref","unstructured":"Rao, Y.L., Ganaraja, B., Murlimanju, B.V., Joy, T., Krishnamurthy, A., and Agrawal, A. (2022). Hippocampus and its involvement in Alzheimer\u2019s disease: A review. 3 Biotech, 12.","DOI":"10.1007\/s13205-022-03123-4"},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"4935","DOI":"10.1093\/brain\/awad232","article-title":"A data-driven study of Alzheimer\u2019s disease related amyloid and tau pathology progression","volume":"146","author":"Aksman","year":"2023","journal-title":"Brain"},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"18062","DOI":"10.1074\/jbc.M116.764795","article-title":"Up-regulation of autophagy-related gene 5 (ATG5) protects dopaminergic neurons in a zebrafish model of Parkinson\u2019s disease","volume":"292","author":"Hu","year":"2017","journal-title":"J. Biol. Chem."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"505","DOI":"10.1001\/jamaneurol.2013.5847","article-title":"Amyloid-\u03b2 and tau: The trigger and bullet in Alzheimer disease pathogenesis","volume":"71","author":"Bloom","year":"2014","journal-title":"JAMA Neurol."},{"key":"ref_97","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_98","doi-asserted-by":"crossref","unstructured":"Guarino, A., Favieri, F., Boncompagni, I., Agostini, F., Cantone, M., and Casagrande, M. (2019). Executive functions in Alzheimer disease: A systematic review. Front. Aging Neurosci., 10.","DOI":"10.3389\/fnagi.2018.00437"},{"key":"ref_99","doi-asserted-by":"crossref","unstructured":"Mosolov, S.N., and Yaltonskaya, P.A. (2022). Primary and Secondary Negative Symptoms in Schizophrenia. Front. Psychiatry, 12.","DOI":"10.3389\/fpsyt.2021.766692"},{"key":"ref_100","first-page":"624","article-title":"Necroptosis: A novel manner of cell death, associated with stroke (Review)","volume":"41","author":"Liu","year":"2018","journal-title":"Int. J. Mol. Med."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"813","DOI":"10.1152\/physrev.00011.2017","article-title":"Neuronal Cell Death","volume":"98","author":"Fricker","year":"2018","journal-title":"Physiol. Rev."},{"key":"ref_102","doi-asserted-by":"crossref","unstructured":"Smith, K., Colie, M., Moore, T., and Schisler, J.C. (2024). Die hard: Necroptosis and its impact on age-dependent neuroinflammatory diseases. Front. Cell Death, 3.","DOI":"10.3389\/fceld.2024.1348153"},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"1009","DOI":"10.1038\/mp.2016.90","article-title":"Postmortem evidence of cerebral inflammation in schizophrenia: A systematic review","volume":"21","author":"Hopperton","year":"2016","journal-title":"Mol. Psychiatry"},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"1002","DOI":"10.1001\/archpsyc.59.11.1002","article-title":"Brain Volume Changes in First-Episode Schizophrenia A 1-Year Follow-up Study","volume":"59","author":"Cahn","year":"2002","journal-title":"Arch. Gen. Psychiatry"},{"key":"ref_105","doi-asserted-by":"crossref","unstructured":"Lu, D., Zhang, W., Li, R., Tan, S., and Zhang, Y. (2025). Targeting necroptosis in Alzheimer\u2019s disease: Can exercise modulate neuronal death?. Front. Aging Neurosci., 17.","DOI":"10.3389\/fnagi.2025.1499871"},{"key":"ref_106","doi-asserted-by":"crossref","unstructured":"Goel, P., Chakrabarti, S., Goel, K., Bhutani, K., Chopra, T., and Bali, S. (2022). Neuronal cell death mechanisms in Alzheimer\u2019s disease: An insight. Front. Mol. Neurosci., 15.","DOI":"10.3389\/fnmol.2022.937133"},{"key":"ref_107","doi-asserted-by":"crossref","unstructured":"Michetti, F., Clementi, M.E., Di Liddo, R., Valeriani, F., Ria, F., Rende, M., Di Sante, G., and Romano Spica, V. (2023). The S100B Protein: A Multifaceted Pathogenic Factor More Than a Biomarker. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms24119605"},{"key":"ref_108","first-page":"2109","article-title":"How S100B crosses brain barriers and why it is considered a peripheral marker of brain injury","volume":"248","author":"Vizuete","year":"2023","journal-title":"Exp. Biol. Med."},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"265","DOI":"10.2174\/1570159X18666200729100427","article-title":"Targeting S100B Protein as a Surrogate Biomarker and its Role in Various Neurological Disorders","volume":"19","author":"Langeh","year":"2020","journal-title":"Curr. Neuropharmacol."},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"539581","DOI":"10.1155\/2010\/539581","article-title":"The S100B\/RAGE axis in Alzheimer\u2019s disease","volume":"2010","author":"Leclerc","year":"2010","journal-title":"Cardiovasc. Psychiatry Neurol."},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"46","DOI":"10.1186\/s12974-022-02412-2","article-title":"The role of S100B\/RAGE-enhanced ADAM17 activation in endothelial glycocalyx shedding after traumatic brain injury","volume":"19","author":"Zou","year":"2022","journal-title":"J. Neuroinflamm."},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"1192","DOI":"10.1007\/s11064-015-1814-8","article-title":"Effects of RAGE-Specific Inhibitor FPS-ZM1 on Amyloid-\u03b2 Metabolism and AGEs-Induced Inflammation and Oxidative Stress in Rat Hippocampus","volume":"41","author":"Hong","year":"2016","journal-title":"Neurochem. Res."},{"key":"ref_113","doi-asserted-by":"crossref","unstructured":"Kozlowski, T., Bargiel, W., Grabarczyk, M., and Skibinska, M. (2023). Peripheral S100B Protein Levels in Five Major Psychiatric Disorders: A Systematic Review. Brain Sci., 13.","DOI":"10.3390\/brainsci13091334"},{"key":"ref_114","doi-asserted-by":"crossref","unstructured":"Sch\u00fcmberg, K., Polyakova, M., Steiner, J., and Schroeter, M.L. (2016). Serum s100b is related to illness duration and clinical symptoms in schizophrenia\u2014A meta-regression analysis. Front. Cell Neurosci., 10.","DOI":"10.3389\/fncel.2016.00046"},{"key":"ref_115","doi-asserted-by":"crossref","unstructured":"Tarasov, V.V., Svistunov, A.A., Chubarev, V.N., Sologova, S.S., Mukhortova, P., Levushkin, D., Somasundaram, S.G., Kirkland, C.E., Bachurin, S.O., and Aliev, G. (2020). Alterations of astrocytes in the context of schizophrenic dementia. Front. Pharmacol., 10.","DOI":"10.3389\/fphar.2019.01612"},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"110927","DOI":"10.1016\/j.brainresbull.2024.110927","article-title":"Serum S100B protein and white matter changes in schizophrenia before and after medication","volume":"210","author":"Shi","year":"2024","journal-title":"Brain Res. Bull."},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1002\/alz.12365","article-title":"Harmonizing neuropsychological assessment for mild neurocognitive disorders in Europe","volume":"18","author":"Boccardi","year":"2022","journal-title":"Alzheimer\u2019s Dement."},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"575","DOI":"10.3233\/JAD-161233","article-title":"Cognitive Domain Dispersion Association with Alzheimer\u2019s Disease Pathology","volume":"58","author":"Lu","year":"2017","journal-title":"J. Alzheimer\u2019s Dis."},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"793","DOI":"10.1080\/13803390903540315","article-title":"Diagnosis of Alzheimer\u2019s disease using neuropsychological testing improved by multivariate analyses","volume":"32","author":"Chapman","year":"2010","journal-title":"J. Clin. Exp. Neuropsychol."},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"e12201","DOI":"10.1002\/trc2.12201","article-title":"Longitudinal cognitive performance of Alzheimer\u2019s disease neuropathological subtypes","volume":"7","author":"Uretsky","year":"2021","journal-title":"Alzheimer\u2019s Dement. Transl. Res. Clin. Interv."},{"key":"ref_121","doi-asserted-by":"crossref","first-page":"e22","DOI":"10.1002\/gps.4731","article-title":"The test of time: A history of clock drawing","volume":"33","author":"Hazan","year":"2018","journal-title":"Int. J. Geriatr. Psychiatry"},{"key":"ref_122","doi-asserted-by":"crossref","first-page":"1315","DOI":"10.3233\/JAD-160771","article-title":"Cognitive Rehabilitation in Alzheimer\u2019s Disease: A Controlled Intervention Trial","volume":"57","author":"Brueggen","year":"2017","journal-title":"J. Alzheimer\u2019s Dis."},{"key":"ref_123","doi-asserted-by":"crossref","first-page":"104807","DOI":"10.1016\/j.archger.2022.104807","article-title":"Cognitive stimulation and cognitive results in older adults: A systematic review and meta-analysis","volume":"104","author":"Iguacel","year":"2023","journal-title":"Arch. Gerontol. Geriatr."},{"key":"ref_124","doi-asserted-by":"crossref","first-page":"146","DOI":"10.1002\/wps.20624","article-title":"Nonsocial and social cognition in schizophrenia: Current evidence and future directions","volume":"18","author":"Green","year":"2019","journal-title":"World Psychiatry"},{"key":"ref_125","doi-asserted-by":"crossref","first-page":"1902","DOI":"10.1038\/s41380-023-01949-9","article-title":"Cognitive impairment in schizophrenia: Aetiology, pathophysiology, and treatment","volume":"28","author":"McCutcheon","year":"2023","journal-title":"Mol. Psychiatry"},{"key":"ref_126","doi-asserted-by":"crossref","first-page":"114926","DOI":"10.1016\/j.psychres.2022.114926","article-title":"A narrative review of treatment interventions to improve cognitive performance in schizophrenia, with an emphasis on at-risk and early course stages","volume":"317","author":"Mayeli","year":"2022","journal-title":"Psychiatry Res."},{"key":"ref_127","doi-asserted-by":"crossref","first-page":"3661","DOI":"10.1017\/S0033291722000319","article-title":"Acceptability of cognitive remediation for schizophrenia: A systematic review and meta-analysis of randomized controlled trials","volume":"53","author":"Vita","year":"2023","journal-title":"Psychol. Med."},{"key":"ref_128","doi-asserted-by":"crossref","first-page":"848","DOI":"10.1001\/jamapsychiatry.2021.0620","article-title":"Effectiveness, Core Elements, and Moderators of Response of Cognitive Remediation for Schizophrenia: A Systematic Review and Meta-analysis of Randomized Clinical Trials","volume":"78","author":"Vita","year":"2021","journal-title":"JAMA Psychiatry"},{"key":"ref_129","doi-asserted-by":"crossref","unstructured":"Pless, A., Ware, D., Saggu, S., Rehman, H., Morgan, J., and Wang, Q. (2023). Understanding neuropsychiatric symptoms in Alzheimer\u2019s disease: Challenges and advances in diagnosis and treatment. Front. Neurosci., 17.","DOI":"10.3389\/fnins.2023.1263771"},{"key":"ref_130","doi-asserted-by":"crossref","first-page":"438","DOI":"10.1186\/s40001-024-02006-z","article-title":"Efficacy of selective serotonin reuptake inhibitors-related antidepressants in Alzheimer\u2019s disease: A meta-analysis","volume":"29","author":"Wang","year":"2024","journal-title":"Eur. J. Med. Res."},{"key":"ref_131","doi-asserted-by":"crossref","unstructured":"Westhoff, M.L.S., Ladwig, J., Heck, J., Sch\u00fclke, R., Groh, A., Deest, M., Bleich, S., Frieling, H., and Jahn, K. (2022). Early detection and prevention of schizophrenic psychosis\u2014A review. Brain Sci., 12.","DOI":"10.3390\/brainsci12010011"},{"key":"ref_132","doi-asserted-by":"crossref","first-page":"262","DOI":"10.1192\/bjp.bp.116.195370","article-title":"Schizophrenia\u2014An anxiety disorder?","volume":"211","author":"Hall","year":"2017","journal-title":"Br. J. Psychiatry"},{"key":"ref_133","doi-asserted-by":"crossref","first-page":"291","DOI":"10.1176\/appi.ajp.2020.20020147","article-title":"On the Origins of Schizophrenia","volume":"177","author":"Kahn","year":"2020","journal-title":"Am. J. Psychiatry"},{"key":"ref_134","doi-asserted-by":"crossref","unstructured":"Di Luzio, M., Pontillo, M., Villa, M., Attardi, A.G., Bellantoni, D., Di Vincenzo, C., and Vicari, S. (2023). Clinical features and comorbidity in very early-onset schizophrenia: A systematic review. Front. Psychiatry, 14.","DOI":"10.3389\/fpsyt.2023.1270799"},{"key":"ref_135","doi-asserted-by":"crossref","unstructured":"Chaves, C., Dursun, S.M., Tusconi, M., and Hallak, J.E.C. (2024). Neuroinflammation and schizophrenia\u2014Is there a link?. Front. Psychiatry, 15.","DOI":"10.3389\/fpsyt.2024.1356975"},{"key":"ref_136","first-page":"243","article-title":"Premorbid adjustment and previous personality in schizophrenic patients","volume":"19","author":"Juan","year":"2005","journal-title":"Eur. J. Psychiatry"},{"key":"ref_137","doi-asserted-by":"crossref","first-page":"417","DOI":"10.1080\/08039480600940029","article-title":"Premorbid personality in schizophrenia spectrum: A prospective study","volume":"60","author":"Mednick","year":"2006","journal-title":"Nord. J. Psychiatry"},{"key":"ref_138","doi-asserted-by":"crossref","first-page":"e2938","DOI":"10.1002\/brb3.2938","article-title":"Personality traits and disorders in Alzheimer\u2019s disease","volume":"13","year":"2023","journal-title":"Brain Behav."},{"key":"ref_139","doi-asserted-by":"crossref","first-page":"187","DOI":"10.1590\/1980-5764-dn-2021-0029","article-title":"Changes in personality traits in patients with Alzheimer\u2019s Disease","volume":"16","author":"Lopes","year":"2022","journal-title":"Dement. Neuropsychol."},{"key":"ref_140","doi-asserted-by":"crossref","first-page":"773","DOI":"10.3233\/JAD-170901","article-title":"Meta-Analysis of Personality Traits in Alzheimer\u2019s Disease: A Comparison with Healthy Subjects","volume":"62","author":"Garramone","year":"2018","journal-title":"J. Alzheimer\u2019s Dis."},{"key":"ref_141","doi-asserted-by":"crossref","first-page":"1153","DOI":"10.3233\/JAD-190459","article-title":"Personality Traits are Related to Selective Cognitive Impairment in Early Alzheimer\u2019s Disease","volume":"71","author":"Rouch","year":"2019","journal-title":"J. Alzheimer\u2019s Dis."},{"key":"ref_142","doi-asserted-by":"crossref","first-page":"78","DOI":"10.1186\/s41235-022-00428-z","article-title":"Positive symptoms of schizophrenia and their relationship with cognitive and emotional executive functions","volume":"7","year":"2022","journal-title":"Cogn. Res. Princ. Implic."},{"key":"ref_143","doi-asserted-by":"crossref","first-page":"531","DOI":"10.2147\/nedt.2006.2.4.531","article-title":"Cognitive deficits and functional outcome in schizophrenia","volume":"2","author":"Bowie","year":"2006","journal-title":"Neuropsychiatr. Dis. Treat."},{"key":"ref_144","doi-asserted-by":"crossref","first-page":"532","DOI":"10.1016\/j.jalz.2011.05.2410","article-title":"Neuropsychiatric symptoms in Alzheimer\u2019s disease","volume":"7","author":"Lyketsos","year":"2011","journal-title":"Alzheimer\u2019s Dement."},{"key":"ref_145","doi-asserted-by":"crossref","first-page":"264","DOI":"10.1016\/j.jad.2015.09.069","article-title":"The prevalence of neuropsychiatric symptoms in Alzheimer\u2019s disease: Systematic review and meta-analysis","volume":"190","author":"Zhao","year":"2016","journal-title":"J. Affect. Disord."},{"key":"ref_146","doi-asserted-by":"crossref","unstructured":"Endres, D., Matysik, M., Feige, B., Venhoff, N., Schweizer, T., Michel, M., Meixensberger, S., Runge, K., Maier, S.J., and Nickel, K. (2020). Diagnosing organic causes of schizophrenia spectrum disorders: Findings from a one-year cohort of the Freiburg diagnostic protocol in psychosis (FDPP). Diagnostics, 10.","DOI":"10.3390\/diagnostics10090691"},{"key":"ref_147","doi-asserted-by":"crossref","first-page":"383","DOI":"10.1093\/schbul\/sbn135","article-title":"Psychiatric comorbidities and schizophrenia","volume":"35","author":"Buckley","year":"2009","journal-title":"Schizophr. Bull."},{"key":"ref_148","doi-asserted-by":"crossref","first-page":"681","DOI":"10.1016\/j.ccc.2017.03.007","article-title":"Neuropsychiatric Aspects of Infectious Diseases: An Update","volume":"33","author":"Munjal","year":"2017","journal-title":"Crit. Care Clin."},{"key":"ref_149","doi-asserted-by":"crossref","first-page":"115","DOI":"10.23937\/2572-3235.1510115","article-title":"Comparison of Brain MRI Findings between Patients with Alzheimer\u2019s Disease and Non-Dementia Psychiatric Disorders in the Elderly","volume":"9","author":"Xinyu","year":"2023","journal-title":"Int. J. Radiol. Imaging Technol."},{"key":"ref_150","doi-asserted-by":"crossref","first-page":"151","DOI":"10.1038\/s41386-022-01426-x","article-title":"Neuroimaging in schizophrenia: An overview of findings and their implications for synaptic changes","volume":"48","author":"Howes","year":"2023","journal-title":"Neuropsychopharmacology"},{"key":"ref_151","doi-asserted-by":"crossref","first-page":"138","DOI":"10.12688\/wellcomeopenres.16022.1","article-title":"What is the functional\/organic distinction actually doing in psychiatry and neurology?","volume":"5","author":"Bell","year":"2020","journal-title":"Wellcome Open Res."},{"key":"ref_152","doi-asserted-by":"crossref","unstructured":"Widing, L., Simonsen, C., Flaaten, C.B., Haatveit, B., Vik, R.K., Wold, K.F., \u00c5sb\u00f8, G., Ueland, T., and Melle, I. (2020). Symptom Profiles in Psychotic Disorder Not Otherwise Specified. Front. Psychiatry, 11.","DOI":"10.3389\/fpsyt.2020.580444"},{"key":"ref_153","doi-asserted-by":"crossref","first-page":"sgad005","DOI":"10.1093\/schizbullopen\/sgad005","article-title":"Long-term Outcomes of People With DSM Psychotic Disorder NOS","volume":"4","author":"Widing","year":"2023","journal-title":"Schizophr. Bull. Open"},{"key":"ref_154","doi-asserted-by":"crossref","first-page":"e70038","DOI":"10.1002\/alz.70038","article-title":"Diagnostic accuracy of plasma p-tau217\/A\u03b242 for Alzheimer\u2019s disease in clinical and community cohorts","volume":"21","author":"Wang","year":"2025","journal-title":"Alzheimer\u2019s Dement."},{"key":"ref_155","doi-asserted-by":"crossref","first-page":"6739","DOI":"10.1007\/s00415-024-12631-7","article-title":"Diagnostic accuracy of automated Lumipulse plasma pTau-217 in Alzheimer\u2019s disease: A real-world study","volume":"271","author":"Cecchetti","year":"2024","journal-title":"J. Neurol."},{"key":"ref_156","doi-asserted-by":"crossref","first-page":"108352","DOI":"10.1016\/j.neuropharm.2020.108352","article-title":"Efficacy of acetylcholinesterase inhibitors in Alzheimer\u2019s disease","volume":"190","author":"Marucci","year":"2021","journal-title":"Neuropharmacology"},{"key":"ref_157","doi-asserted-by":"crossref","first-page":"379","DOI":"10.18071\/isz.74.0379","article-title":"Cholinesterase Inhibitors and Memantine for the Treatment of Alzheimer and Non-Alzheimer Dementias","volume":"74","author":"Bereczki","year":"2021","journal-title":"Ideggyogy. Szle."},{"key":"ref_158","doi-asserted-by":"crossref","first-page":"1515","DOI":"10.2165\/00003495-200666110-00015","article-title":"Memantine: A Review of its Use in Alzheimer\u2019s Disease","volume":"66","author":"Robinson","year":"2006","journal-title":"Drugs"},{"key":"ref_159","doi-asserted-by":"crossref","first-page":"1333","DOI":"10.1056\/NEJMoa013128","article-title":"Memantine in Moderate-to-Severe Alzheimer\u2019s Disease","volume":"14","author":"Reisberg","year":"2003","journal-title":"N. Engl. J. Med."},{"key":"ref_160","first-page":"1333","article-title":"Neuroprotective properties of memantine in different in vitro and in vivo models of excitotoxicity","volume":"348","author":"Volbracht","year":"2006","journal-title":"Eur. J. Neurosci."},{"key":"ref_161","doi-asserted-by":"crossref","unstructured":"Weston-Green, K. (2022). Antipsychotic Drug Development: From Historical Evidence to Fresh Perspectives. Front. Psychiatry, 13.","DOI":"10.3389\/fpsyt.2022.903156"},{"key":"ref_162","doi-asserted-by":"crossref","first-page":"375","DOI":"10.1017\/S1092852917000608","article-title":"Drugs for psychosis and mood: Unique actions at D3, D2, and D1 dopamine receptor subtypes","volume":"22","author":"Stahl","year":"2017","journal-title":"CNS Spectr."},{"key":"ref_163","doi-asserted-by":"crossref","first-page":"488","DOI":"10.2174\/138161210790361461","article-title":"Third generation antipsychotic drugs: Partial agonism or receptor functional selectivity?","volume":"16","author":"Mailman","year":"2010","journal-title":"Curr. Pharm. Des."},{"key":"ref_164","doi-asserted-by":"crossref","first-page":"583","DOI":"10.1176\/appi.ajp.2008.08081218","article-title":"Metabolic changes associated with second-generation antipsychotic use in Alzheimer\u2019s disease patients: The CATIE-AD study","volume":"166","author":"Zheng","year":"2009","journal-title":"Am. J. Psychiatry"},{"key":"ref_165","doi-asserted-by":"crossref","first-page":"154","DOI":"10.9740\/mhc.n166832","article-title":"Strategies for prevention and management of second generation antipsychotic-induced metabolic side effects","volume":"3","author":"Marvanova","year":"2013","journal-title":"Ment. Health Clin."},{"key":"ref_166","doi-asserted-by":"crossref","first-page":"e204693","DOI":"10.1001\/jamanetworkopen.2020.4693","article-title":"Association of Ketamine with Psychiatric Symptoms and Implications for Its Therapeutic Use and for Understanding Schizophrenia: A Systematic Review and Meta-analysis","volume":"3","author":"Beck","year":"2020","journal-title":"JAMA Netw. Open"},{"key":"ref_167","doi-asserted-by":"crossref","first-page":"920","DOI":"10.1093\/schbul\/sbs076","article-title":"NMDA receptor and schizophrenia: A brief history","volume":"38","author":"Coyle","year":"2012","journal-title":"Schizophr. Bull."},{"key":"ref_168","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1016\/S0924-977X(96)00039-9","article-title":"Metabolic hyperfrontality and psychopathology in the ketamine model of psychosis using positron emission tomography (PET) and [18F]fluorodeoxyglucose (FDG)","volume":"7","author":"Vollenweider","year":"1997","journal-title":"Eur. Neuropsychopharmacol."},{"key":"ref_169","doi-asserted-by":"crossref","first-page":"455","DOI":"10.1016\/S0893-133X(01)00243-3","article-title":"Effects of Ketamine in Normal and Schizophrenic Volunteers","volume":"25","author":"Lahti","year":"2001","journal-title":"Neuropsychopharmacology"},{"key":"ref_170","doi-asserted-by":"crossref","unstructured":"Carolan, A., Hynes-Ryan, C., Agarwal, S.M., Bourke, R., Cullen, W., Gaughran, F., Hahn, M.K., Krivoy, A., Lally, J., and Leucht, S. (2024). Metformin for the Prevention of Antipsychotic-Induced Weight Gain: Guideline Development and Consensus Validation. Schizophr. Bull., sbae205.","DOI":"10.1093\/schbul\/sbae205"},{"key":"ref_171","doi-asserted-by":"crossref","first-page":"100","DOI":"10.1007\/s11920-019-1091-3","article-title":"Non-Genetic Factors in Schizophrenia","volume":"21","author":"Stilo","year":"2019","journal-title":"Curr. Psychiatry Rep."},{"key":"ref_172","doi-asserted-by":"crossref","unstructured":"Robinson, N., and Bergen, S.E. (2021). Environmental Risk Factors for Schizophrenia and Bipolar Disorder and Their Relationship to Genetic Risk: Current Knowledge and Future Directions. Front. Genet., 12.","DOI":"10.3389\/fgene.2021.686666"},{"key":"ref_173","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1016\/j.pneurobio.2010.09.003","article-title":"The environment and susceptibility to schizophrenia","volume":"93","author":"Brown","year":"2011","journal-title":"Prog. Neurobiol."},{"key":"ref_174","doi-asserted-by":"crossref","unstructured":"Gao, X., Chen, Q., Yao, H., Tan, J., Liu, Z., Zhou, Y., and Zou, Z. (2022). Epigenetics in Alzheimer\u2019s Disease. Front. Aging Neurosci., 14.","DOI":"10.3389\/fnagi.2022.911635"},{"key":"ref_175","doi-asserted-by":"crossref","unstructured":"Hong, W., Zhao, M., Li, H., Peng, F., Wang, F., Li, N., Xiang, H., Su, Y., Huang, Y., and Zhang, S. (2016). Higher Plasma S100B Concentrations in Schizophrenia Patients, and Dependently Associated with Inflammatory Markers. Sci. Rep., 6.","DOI":"10.1038\/srep27584"},{"key":"ref_176","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1590\/S0101-60832012005000008","article-title":"Potential roles of S100B in schizophrenia","volume":"40","author":"Steiner","year":"2013","journal-title":"Rev. Psiquiatr. Cl\u00edn."},{"key":"ref_177","doi-asserted-by":"crossref","unstructured":"Mucci, A., Kawohl, W., Maria, C., and Wooller, A. (2020). Treating Schizophrenia: Open Conversations and Stronger Relationships Through Psychoeducation and Shared Decision-Making. Front. Psychiatry, 11.","DOI":"10.3389\/fpsyt.2020.00761"},{"key":"ref_178","doi-asserted-by":"crossref","unstructured":"Kulji\u0161, R.O., Colom, L.V., and Rojo, L.E. (2014). Biological Basis for Cerebral Dysfunction in Schizophrenia in Contrast with Alzheimer\u2019s Disease. Front. Psychiatry, 4.","DOI":"10.3389\/fpsyt.2013.00119"},{"key":"ref_179","doi-asserted-by":"crossref","unstructured":"Ting, C., Rajji, T.K., Ismail, Z., Tang-Wai, D.F., Apanasiewicz, N., Miranda, D., Mamo, D., and Mulsant, B.H. (2010). Differentiating the cognitive profile of schizophrenia from that of Alzheimer disease and depression in late life. PLoS ONE, 5.","DOI":"10.1371\/journal.pone.0010151"},{"key":"ref_180","doi-asserted-by":"crossref","first-page":"S64","DOI":"10.1093\/schbul\/sbl030","article-title":"Efficacy of psychological therapy in schizophrenia: Conclusions from meta-analyses","volume":"32","author":"Pfammatter","year":"2006","journal-title":"Schizophr. Bull."},{"key":"ref_181","first-page":"3","article-title":"The Role of the Psychiatrist in Alzheimer\u2019s Disease","volume":"59","author":"Lake","year":"1998","journal-title":"J. Clin. Psychiatry"},{"key":"ref_182","doi-asserted-by":"crossref","unstructured":"Fan, P., Kofler, J., Ding, Y., Marks, M., Sweet, R.A., and Wang, L. (2022). Efficacy difference of antipsychotics in Alzheimer\u2019s disease and schizophrenia: Explained with network efficiency and pathway analysis methods. Brief. Bioinform., 23.","DOI":"10.1093\/bib\/bbac394"},{"key":"ref_183","doi-asserted-by":"crossref","unstructured":"Beata, B.K., Wojciech, J., Johannes, K., Piotr, L., and Barbara, M. (2023). Alzheimer\u2019s Disease\u2014Biochemical and Psychological Background for Diagnosis and Treatment. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms24021059"},{"key":"ref_184","doi-asserted-by":"crossref","unstructured":"Svensson, J.E., Bolin, M., Thor, D., Williams, P.A., Brautaset, R., Carlsson, M., S\u00f6rensson, P., Marlevi, D., Spin-Neto, R., and Probst, M. (2024). Evaluating the effect of rapamycin treatment in Alzheimer\u2019s disease and aging using in vivo imaging: The ERAP phase IIa clinical study protocol. BMC Neurol., 24.","DOI":"10.1186\/s12883-024-03596-1"},{"key":"ref_185","doi-asserted-by":"crossref","first-page":"1629","DOI":"10.2147\/CIA.S429440","article-title":"Rapamycin Responds to Alzheimer\u2019s Disease: A Potential Translational Therapy","volume":"18","author":"Hou","year":"2023","journal-title":"Clin. Interv. Aging"},{"key":"ref_186","doi-asserted-by":"crossref","unstructured":"Xie, P.L., Zheng, M.Y., Han, R., Chen, W.X., and Mao, J.H. (2024). Pharmacological mTOR inhibitors in ameliorating Alzheimer\u2019s disease: Current review and perspectives. Front. Pharmacol., 15.","DOI":"10.3389\/fphar.2024.1366061"},{"key":"ref_187","doi-asserted-by":"crossref","unstructured":"Lee, J., Yanckello, L.M., Ma, D., Hoffman, J.D., Parikh, I., Thalman, S., Bauer, B., Hartz, A.M.S., Hyder, F., and Lin, A.L. (2018). Neuroimaging Biomarkers of mTOR Inhibition on Vascular and Metabolic Functions in Aging Brain and Alzheimer\u2019s Disease. Front. Aging Neurosci., 10.","DOI":"10.3389\/fnagi.2018.00225"},{"key":"ref_188","doi-asserted-by":"crossref","unstructured":"Poor, S.R., Ettcheto, M., Cano, A., Sanchez-Lopez, E., Manzine, P.R., Olloquequi, J., Camins, A., and Javan, M. (2021). Metformin a potential pharmacological strategy in late onset Alzheimer\u2019s disease treatment. Pharmaceuticals, 14.","DOI":"10.3390\/ph14090890"},{"key":"ref_189","first-page":"100118","article-title":"Beyond one-size-fits-all: The rise of personalized treatment in schizophrenia","volume":"43\u201344","author":"Nashwan","year":"2024","journal-title":"Pers. Med. Psychiatry"},{"key":"ref_190","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1038\/s41537-016-0001-5","article-title":"Personalized medicine for schizophrenia","volume":"3","author":"Buckley","year":"2017","journal-title":"npj Schizophr."},{"key":"ref_191","doi-asserted-by":"crossref","first-page":"78","DOI":"10.1192\/apt.bp.114.013433","article-title":"Personalised approaches to pharmacotherapy for schizophrenia","volume":"22","author":"Lally","year":"2016","journal-title":"BJPsych Adv."},{"key":"ref_192","doi-asserted-by":"crossref","first-page":"3663","DOI":"10.2147\/NDT.S337814","article-title":"From Personalized Medicine to Precision Psychiatry?","volume":"17","year":"2021","journal-title":"Neuropsychiatr. Dis. Treat."},{"key":"ref_193","doi-asserted-by":"crossref","first-page":"187","DOI":"10.1016\/j.psc.2016.01.003","article-title":"The Case for Adjunctive Monoclonal Antibody Immunotherapy in Schizophrenia","volume":"39","author":"Miller","year":"2016","journal-title":"Psychiatr. Clin. N. Am."},{"key":"ref_194","doi-asserted-by":"crossref","first-page":"1441","DOI":"10.1080\/14737175.2021.1994857","article-title":"Pharmacotherapy of schizophrenia: Immunological aspects and potential role of immunotherapy","volume":"21","author":"Chauhan","year":"2021","journal-title":"Expert Rev. Neurother."},{"key":"ref_195","doi-asserted-by":"crossref","first-page":"3568","DOI":"10.1038\/s41380-023-02265-y","article-title":"GRIN2A (NR2A): A gene contributing to glutamatergic involvement in schizophrenia","volume":"28","author":"Harrison","year":"2023","journal-title":"Mol. Psychiatry"},{"key":"ref_196","doi-asserted-by":"crossref","first-page":"92","DOI":"10.1038\/s41398-023-02393-7","article-title":"Mouse mutants in schizophrenia risk genes GRIN2A and AKAP11 show EEG abnormalities in common with schizophrenia patients","volume":"13","author":"Herzog","year":"2023","journal-title":"Transl. Psychiatry"},{"key":"ref_197","doi-asserted-by":"crossref","unstructured":"Shepard, N., Baez-Nieto, D., Iqbal, S., Kurganov, E., Budnik, N., Campbell, A.J., Pan, J.Q., Sheng, M., and Farsi, Z. (2024). Differential functional consequences of GRIN2A mutations associated with schizophrenia and neurodevelopmental disorders. Sci. Rep., 14.","DOI":"10.1038\/s41598-024-53102-3"}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/26\/13\/6237\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T18:00:37Z","timestamp":1760032837000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/26\/13\/6237"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,6,27]]},"references-count":197,"journal-issue":{"issue":"13","published-online":{"date-parts":[[2025,7]]}},"alternative-id":["ijms26136237"],"URL":"https:\/\/doi.org\/10.3390\/ijms26136237","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,6,27]]}}}