{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,27]],"date-time":"2026-08-27T10:52:18Z","timestamp":1787827938708,"version":"build-2784847793"},"reference-count":49,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2025,9,4]],"date-time":"2025-09-04T00:00:00Z","timestamp":1756944000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2025,9,4]],"date-time":"2025-09-04T00:00:00Z","timestamp":1756944000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100006087","name":"Direcci\u00f3n General de Asuntos del Personal Acad\u00e9mico, Universidad Nacional Aut\u00f3noma de M\u00e9xico","doi-asserted-by":"crossref","award":["IN203322 and IN209025"],"award-info":[{"award-number":["IN203322 and IN209025"]}],"id":[{"id":"10.13039\/501100006087","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Neuromol Med"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>It is now widely accepted that the development of neurodegenerative diseases depends on and affects many pathological processes, both in the brain and the periphery. Inflammatory, cardiovascular, metabolic, cerebrovascular, autoimmune, and other environmental factors have been extensively studied and shown to contribute notably to the onset, pathogenesis, and clinical outcome of Alzheimer\u00b4s disease (AD), Parkinson\u00b4s disease (PD), cerebral amyloid angiopathy (CAA), multiple sclerosis, and other neurological disorders. Likewise, AD-induced changes in other tissues outside the central nervous system, such as abnormalities observed in the liver, spleen, or lungs, have been documented and extensively studied, leading to a better understanding of brain-periphery crosstalk in neurodegenerative diseases and the development of novel diagnostic and therapeutic approaches. In this study, we documented striking differences in the periphery in two frequently used, well-established APP transgenic mouse models of AD: 3xTg-AD mice, harboring three human genes (APP, tau, and Psen1), and Tg-SwDI mice, expressing human APP with the Swedish and vasculotropic Dutch\/Iowa mutations in the brain. We documented splenomegaly, immunoglobulin-associated spleen amyloidosis, and an increase in the percentage of neutrophils in the spleen and macrophages in the liver in 3xTg-AD mice but not in age-matched Tg-SwDI mice, which are commonly used as an AD\/CAA model. Our data suggest that the results observed in any transgenic mouse strain should be taken into account with caution. A detailed knowledge of pathological characteristics recapitulated in a particular strain can help to determine which mice are more appropriate for studying a specific mechanism or therapeutic approach.<\/jats:p>","DOI":"10.1007\/s12017-025-08884-8","type":"journal-article","created":{"date-parts":[[2025,9,4]],"date-time":"2025-09-04T04:34:05Z","timestamp":1756960445000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Splenomegaly, Spleen Amyloidosis and Neutrophil Infiltration are Present in 3xTg-AD, but not Tg-SwDI Mice"],"prefix":"10.1007","volume":"27","author":[{"given":"Gonzalo","family":"Acero","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adrian","family":"Rodriguez-Lopez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Georgina","family":"D\u00edaz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel","family":"Esteban","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M\u00f3nica","family":"Herrera-\u00c1ngeles","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Goar","family":"Gevorkian","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,9,4]]},"reference":[{"key":"8884_CR1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbr.2022.114189","volume":"438","author":"R Baeta-Corral","year":"2023","unstructured":"Baeta-Corral, R., De la Fuente, M., & Gim\u00e9nez-Llort, L. (2023). Sex-dependent worsening of NMDA-induced responses, anxiety, hypercortisolemia, and organometry of early peripheral immunoendocrine impairment in adult 3xTg-AD mice and their long-lasting ontogenic modulation by neonatal handling. Behavioural Brain Research, 438, Article 114189. https:\/\/doi.org\/10.1016\/j.bbr.2022.114189","journal-title":"Behavioural Brain Research"},{"key":"8884_CR2","doi-asserted-by":"publisher","first-page":"79","DOI":"10.3389\/fphar.2018.00079","volume":"9","author":"R Baeta-Corral","year":"2018","unstructured":"Baeta-Corral, R., Johansson, B., & Gim\u00e9nez-Llort, L. (2018). Long-term treatment with low-dose caffeine worsens BPSD-like profile in 3xTg-AD mice model of Alzheimer\u2019s disease and affects mice with normal aging. Frontiers in Pharmacology, 9, 79. https:\/\/doi.org\/10.3389\/fphar.2018.00079","journal-title":"Frontiers in Pharmacology"},{"issue":"1","key":"8884_CR3","doi-asserted-by":"publisher","first-page":"134","DOI":"10.1186\/s13195-024-01492-x","volume":"16","author":"AJ Barber","year":"2024","unstructured":"Barber, A. J., Del Genio, C. L., Swain, A. B., Pizzi, E. M., Watson, S. C., Tapiavala, V. N., et al. (2024). Age, sex and Alzheimer\u2019s disease: A longitudinal study of 3xTg-AD mice reveals sex-specific disease trajectories and inflammatory responses mirrored in postmortem brains from Alzheimer\u2019s patients. Alzheimer\u2019s Research & Therapy, 16(1), 134. https:\/\/doi.org\/10.1186\/s13195-024-01492-x","journal-title":"Alzheimer's Research & Therapy"},{"issue":"1","key":"8884_CR4","doi-asserted-by":"publisher","DOI":"10.1111\/acel.12873","volume":"18","author":"R Belfiore","year":"2019","unstructured":"Belfiore, R., Rodin, A., Ferreira, E., Velazquez, R., Branca, C., Caccamo, A., et al. (2019). Temporal and regional progression of Alzheimer\u2019s disease-like pathology in 3xTg-AD mice. Aging Cell, 18(1), Article e12873. https:\/\/doi.org\/10.1111\/acel.12873","journal-title":"Aging Cell"},{"issue":"1","key":"8884_CR5","doi-asserted-by":"publisher","first-page":"37","DOI":"10.1007\/s00418-019-01827-y","volume":"153","author":"SA Bloomer","year":"2020","unstructured":"Bloomer, S. A., Moyer, E. D., Brown, K. E., & Kregel, K. C. (2020). Aging results in accumulation of M1 and M2 hepatic macrophages and a differential response to gadolinium chloride. Histochemistry and Cell Biology, 153(1), 37\u201348. https:\/\/doi.org\/10.1007\/s00418-019-01827-y","journal-title":"Histochemistry and Cell Biology"},{"issue":"1","key":"8884_CR6","doi-asserted-by":"publisher","first-page":"74","DOI":"10.1097\/PAS.0000000000001948","volume":"47","author":"A Chiu","year":"2023","unstructured":"Chiu, A., Dasari, S., Kurtin, P. J., Theis, J. D., Vrana, J. A., Rech, K. L., et al. (2023). Proteomic identification and clinicopathologic characterization of splenic amyloidosis. The American Journal of Surgical Pathology, 47(1), 74\u201380. https:\/\/doi.org\/10.1097\/PAS.0000000000001948","journal-title":"The American Journal of Surgical Pathology"},{"issue":"19","key":"8884_CR7","doi-asserted-by":"publisher","first-page":"20296","DOI":"10.1074\/jbc.M312946200","volume":"279","author":"J Davis","year":"2004","unstructured":"Davis, J., Xu, F., Deane, R., Romanov, G., Previti, M. L., Zeigler, K., et al. (2004). Early-onset and robust cerebral microvascular accumulation of amyloid beta-protein in transgenic mice expressing low levels of a vasculotropic Dutch\/Iowa mutant form of amyloid beta-protein precursor. Journal of Biological Chemistry, 279(19), 20296\u201320306. https:\/\/doi.org\/10.1074\/jbc.M312946200","journal-title":"Journal of Biological Chemistry"},{"issue":"7","key":"8884_CR8","doi-asserted-by":"publisher","first-page":"946","DOI":"10.1016\/j.neurobiolaging.2005.05.031","volume":"27","author":"J Davis","year":"2006","unstructured":"Davis, J., Xu, F., Miao, J., Previti, M. L., Romanov, G., Ziegler, K., et al. (2006). Deficient cerebral clearance of vasculotropic mutant Dutch\/Iowa double A beta in human A betaPP transgenic mice. Neurobiology of Aging, 27(7), 946\u2013954. https:\/\/doi.org\/10.1016\/j.neurobiolaging.2005.05.031","journal-title":"Neurobiology of Aging"},{"issue":"11","key":"8884_CR9","doi-asserted-by":"publisher","first-page":"1405","DOI":"10.3390\/biom14111405","volume":"14","author":"LM De Plano","year":"2024","unstructured":"De Plano, L. M., Saitta, A., Oddo, S., & Caccamo, A. (2024). Navigating Alzheimer\u2019s disease mouse models: Age-related pathology and cognitive deficits. Biomolecules, 14(11), 1405. https:\/\/doi.org\/10.3390\/biom14111405","journal-title":"Biomolecules"},{"issue":"11","key":"8884_CR10","doi-asserted-by":"publisher","first-page":"6112","DOI":"10.3390\/ijms25116112","volume":"25","author":"J Fraile-Ramos","year":"2024","unstructured":"Fraile-Ramos, J., Reig-Vilallonga, J., & Gim\u00e9nez-Llort, L. (2024). Glomerular hypertrophy and splenic red pulp degeneration concurrent with oxidative stress in 3xTg-AD mice model for Alzheimer\u2019s disease and its exacerbation with sex and social isolation. International Journal of Molecular Sciences, 25(11), 6112. https:\/\/doi.org\/10.3390\/ijms25116112","journal-title":"International Journal of Molecular Sciences"},{"issue":"14","key":"8884_CR11","doi-asserted-by":"publisher","first-page":"11332","DOI":"10.3390\/ijms241411332","volume":"24","author":"L Freire-Antunes","year":"2023","unstructured":"Freire-Antunes, L., Ornellas-Garcia, U., Rangel-Ferreira, M. V., Ribeiro-Almeida, M. L., de Sousa, C. H. G., Carvalho, L. J. M., et al. (2023). Increased neutrophil percentage and Neutrophil-T cell ratio precedes clinical onset of experimental cerebral malaria. International Journal of Molecular Sciences, 24(14), 11332. https:\/\/doi.org\/10.3390\/ijms241411332","journal-title":"International Journal of Molecular Sciences"},{"key":"8884_CR12","doi-asserted-by":"publisher","first-page":"331","DOI":"10.1159\/000156475","volume":"15","author":"L Gim\u00e9nez-Llort","year":"2008","unstructured":"Gim\u00e9nez-Llort, L., Arranz, L., Mat\u00e9, I., & De la Fuente, M. (2008). Gender-specific neuroimmunoendocrine aging in a triple-transgenic 3xTg-AD mouse model for Alzheimer\u2019s disease and its relation with longevity. NeuroImmunoModulation, 15, 331\u2013343. https:\/\/doi.org\/10.1159\/000156475","journal-title":"NeuroImmunoModulation"},{"issue":"s1","key":"8884_CR13","doi-asserted-by":"publisher","first-page":"S107","DOI":"10.3233\/JAD-179921","volume":"64","author":"C-X Gong","year":"2018","unstructured":"Gong, C.-X., Liu, F., & Iqbal, K. (2018). Multifactorial hypothesis and multi-targets for Alzheimer\u2019s disease. Journal of Alzheimer\u2019s Disease, 64(s1), S107\u2013S117. https:\/\/doi.org\/10.3233\/JAD-179921","journal-title":"Journal of Alzheimer's Disease"},{"key":"8884_CR14","doi-asserted-by":"publisher","first-page":"13","DOI":"10.1016\/j.semcdb.2022.05.028","volume":"139","author":"J Griffiths","year":"2022","unstructured":"Griffiths, J., & Grant, S. G. N. (2022). Synapse pathology in Alzheimer\u2019s disease. Seminars in Cell & Developmental Biology, 139, 13\u201323. https:\/\/doi.org\/10.1016\/j.semcdb.2022.05.028","journal-title":"Seminars in Cell & Developmental Biology"},{"issue":"3","key":"8884_CR15","doi-asserted-by":"publisher","DOI":"10.1093\/jleuko\/qiae220","volume":"117","author":"R Guo","year":"2025","unstructured":"Guo, R., Xie, X., Ren, Q., & Liew, P. X. (2025). New insights on extramedullary granulopoiesis and neutrophil heterogeneity in the spleen and its importance in disease. Journal of Leukocyte Biology, 117(3), Article qiae220. https:\/\/doi.org\/10.1093\/jleuko\/qiae220","journal-title":"Journal of Leukocyte Biology"},{"issue":"8","key":"8884_CR16","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0042344","volume":"7","author":"LF Hernandez-Zimbron","year":"2012","unstructured":"Hernandez-Zimbron, L. F., Luna-Mu\u00f1oz, J., Mena, R., Vazquez-Ramirez, R., Kubli-Garfias, C., Cribbs, D. H., et al. (2012). Amyloid-\u03b2 peptide binds to cytochrome c oxidase subunit 1. PLoS ONE, 7(8), Article e42344. https:\/\/doi.org\/10.1371\/journal.pone.0042344","journal-title":"PLoS ONE"},{"issue":"5","key":"8884_CR17","doi-asserted-by":"publisher","first-page":"420","DOI":"10.1016\/j.jalz.2010.04.006","volume":"6","author":"K Iqbal","year":"2010","unstructured":"Iqbal, K., & Grundke-Iqbal, I. (2010). Alzheimer disease, a multifactorial disorder seeking multitherapies. Alzheimer\u2019s & Dementia, 6(5), 420\u2013424. https:\/\/doi.org\/10.1016\/j.jalz.2010.04.006","journal-title":"Alzheimer's & Dementia"},{"issue":"1","key":"8884_CR18","doi-asserted-by":"publisher","first-page":"30","DOI":"10.1186\/s13195-020-00745-9","volume":"13","author":"M Kapadia","year":"2021","unstructured":"Kapadia, M., Mian, M. F., Ma, D., Hutton, C. P., Azam, A., Narkaj, K., et al. (2021). Differential effects of chronic immunosuppression on behavioral, epigenetic, and Alzheimer\u2019s disease-associated markers in 3xTg-AD mice. Alzheimer\u2019s Research & Therapy, 13(1), 30. https:\/\/doi.org\/10.1186\/s13195-020-00745-9","journal-title":"Alzheimer's Research & Therapy"},{"key":"8884_CR19","doi-asserted-by":"publisher","first-page":"1191","DOI":"10.3233\/JAD-170779","volume":"63","author":"M Kapadia","year":"2018","unstructured":"Kapadia, M., Mian, M. F., Michalski, B., Azam, A. B., Ma, D., Salwierz, P., et al. (2018). Sex-dependent differences in spontaneous autoimmunity in adult 3xTg-AD mice. Journal of Alzheimer\u2019s Disease, 63, 1191\u20131205. https:\/\/doi.org\/10.3233\/JAD-170779","journal-title":"Journal of Alzheimer's Disease"},{"issue":"3","key":"8884_CR20","doi-asserted-by":"publisher","first-page":"159","DOI":"10.1038\/nri3399","volume":"13","author":"E Kolaczkowska","year":"2013","unstructured":"Kolaczkowska, E., & Kubes, P. (2013). Neutrophil recruitment and function in health and inflammation. Nature Reviews Immunology, 13(3), 159\u2013175. https:\/\/doi.org\/10.1038\/nri3399","journal-title":"Nature Reviews Immunology"},{"issue":"6","key":"8884_CR21","doi-asserted-by":"publisher","first-page":"2589","DOI":"10.7150\/thno.93812","volume":"14","author":"C Liao","year":"2024","unstructured":"Liao, C., Luo, S., Liu, X., Zhang, L., Xie, P., Zhou, W., et al. (2024). Siglec-F+ neutrophils in the spleen induce immunosuppression following acute infection. Theranostics, 14(6), 2589\u20132604. https:\/\/doi.org\/10.7150\/thno.93812","journal-title":"Theranostics"},{"key":"8884_CR22","doi-asserted-by":"publisher","DOI":"10.3389\/fncel.2021.652111","volume":"15","author":"J Lutshumba","year":"2021","unstructured":"Lutshumba, J., Nikolajczyk, B. S., & Bachstetter, A. D. (2021). Dysregulation of systemic immunity in aging and dementia. Frontiers in Cellular Neuroscience, 15, Article 652111. https:\/\/doi.org\/10.3389\/fncel.2021.652111","journal-title":"Frontiers in Cellular Neuroscience"},{"key":"8884_CR23","doi-asserted-by":"publisher","first-page":"156","DOI":"10.1016\/j.jad.2022.08.087","volume":"317","author":"L Ma","year":"2022","unstructured":"Ma, L., Zhang, J., Fujita, Y., Shinno-Hashimoto, H., Shan, J., Wan, X., et al. (2022). Effects of spleen nerve denervation on depression-like phenotype, systemic inflammation, and abnormal composition of gut microbiota in mice after administration of lipopolysaccharide: A role of brain-spleen axis. Journal of Affective Disorders, 317, 156\u2013165. https:\/\/doi.org\/10.1016\/j.jad.2022.08.087","journal-title":"Journal of Affective Disorders"},{"issue":"9","key":"8884_CR24","doi-asserted-by":"publisher","first-page":"985","DOI":"10.2174\/1567205013666160427101832","volume":"13","author":"M Magistri","year":"2016","unstructured":"Magistri, M., Velmeshev, D., Makhmutova, M., Patel, P., Sartor, G. C., Volmar, C. H., et al. (2016). The BET-bromodomain inhibitor JQ1 reduces inflammation and tau phosphorylation at Ser396 in the brain of the 3xTg model of Alzheimer\u2019s disease. Current Alzheimer Research, 13(9), 985\u2013995. https:\/\/doi.org\/10.2174\/1567205013666160427101832","journal-title":"Current Alzheimer Research"},{"issue":"6","key":"8884_CR25","doi-asserted-by":"publisher","first-page":"899","DOI":"10.3390\/antiox10060899","volume":"1","author":"J Manna","year":"2021","unstructured":"Manna, J., Dunbar, G. L., & Maiti, P. (2021). Curcugreen treatment prevented splenomegaly and other peripheral organ abnormalities in 3xTg and 5xFAD mouse models of alzheimer\u2019s disease. Antioxidants (Basel), 1(6), 899. https:\/\/doi.org\/10.3390\/antiox10060899","journal-title":"Antioxidants (Basel)"},{"key":"8884_CR26","doi-asserted-by":"publisher","first-page":"191","DOI":"10.3233\/JAD-131490","volume":"39","author":"M Marchese","year":"2014","unstructured":"Marchese, M., Cowan, D., Head, E., Ma, D., Karimi, K., Ashthorpe, V., et al. (2014). Autoimmune manifestations in the 3xTg-AD model of Alzheimer\u2019s disease. Journal of Alzheimer\u2019s Disease, 39, 191\u2013210. https:\/\/doi.org\/10.3233\/JAD-131490","journal-title":"Journal of Alzheimer's Disease"},{"key":"8884_CR27","doi-asserted-by":"publisher","first-page":"81","DOI":"10.1186\/1471-2202-9-81","volume":"9","author":"MA Mastrangelo","year":"2008","unstructured":"Mastrangelo, M. A., & Bowers, W. J. (2008). Detailed immunohistochemical characterization of temporal and spatial progression of Alzheimer\u2019s disease-related pathologies in male triple-transgenic mice. BMC Neuroscience, 9, 81. https:\/\/doi.org\/10.1186\/1471-2202-9-81","journal-title":"BMC Neuroscience"},{"issue":"2","key":"8884_CR28","doi-asserted-by":"publisher","first-page":"505","DOI":"10.1016\/s0002-9440(10)62993-8","volume":"167","author":"J Miao","year":"2005","unstructured":"Miao, J., Xu, F., Davis, J., Otte-H\u00f6ller, I., Verbeek, M. M., & Van Nostrand, W. E. (2005). Cerebral microvascular amyloid beta protein deposition induces vascular degeneration and neuroinflammation in transgenic mice expressing human vasculotropic mutant amyloid beta precursor protein. The American Journal of Pathology, 167(2), 505\u2013515. https:\/\/doi.org\/10.1016\/s0002-9440(10)62993-8","journal-title":"The American Journal of Pathology"},{"key":"8884_CR29","doi-asserted-by":"publisher","DOI":"10.1016\/j.jneuroim.2021.577720","volume":"360","author":"M Nava Catorce","year":"2021","unstructured":"Nava Catorce, M., Acero, G., & Gevorkian, G. (2021). Age- and sex-dependent alterations in the peripheral immune system in the 3xTg-AD mouse model of Alzheimer\u2019s disease: Increased proportion of CD3+CD4-CD8- double-negative T cells in the blood. Journal of Neuroimmunology, 360, Article 577720. https:\/\/doi.org\/10.1016\/j.jneuroim.2021.577720","journal-title":"Journal of Neuroimmunology"},{"issue":"2","key":"8884_CR30","doi-asserted-by":"publisher","first-page":"587","DOI":"10.3233\/JAD-190853","volume":"72","author":"K Nitzan","year":"2019","unstructured":"Nitzan, K., Benhamron, S., Valitsky, M., Kesner, E. E., Lichtenstein, M., Ben-Zvi, A., et al. (2019). Mitochondrial transfer ameliorates cognitive deficits, neuronal loss, and gliosis in Alzheimer\u2019s disease mice. Journal of Alzheimer\u2019s Disease, 72(2), 587\u2013604. https:\/\/doi.org\/10.3233\/JAD-190853","journal-title":"Journal of Alzheimer's Disease"},{"key":"8884_CR31","doi-asserted-by":"publisher","first-page":"409","DOI":"10.1016\/s0896-6273(03)00434-3","volume":"39","author":"S Oddo","year":"2003","unstructured":"Oddo, S., Caccamo, A., Shepherd, J. D., Murphy, M. P., Golde, T. E., Kayed, R., et al. (2003). Triple-transgenic model of Alzheimer\u2019s disease with plaques and tangles: Intracellular Abeta and synaptic dysfunction. Neuron, 39, 409\u2013421. https:\/\/doi.org\/10.1016\/s0896-6273(03)00434-3","journal-title":"Neuron"},{"issue":"6","key":"8884_CR32","doi-asserted-by":"publisher","first-page":"1815","DOI":"10.1161\/STROKEAHA.114.005179","volume":"45","author":"L Park","year":"2014","unstructured":"Park, L., Koizumi, K., El Jamal, S., Zhou, P., Previti, M. L., Van Nostrand, W. E., et al. (2014). Age-dependent neurovascular dysfunction and damage in a mouse model of cerebral amyloid angiopathy. Stroke, 45(6), 1815\u20131821. https:\/\/doi.org\/10.1161\/STROKEAHA.114.005179","journal-title":"Stroke"},{"key":"8884_CR33","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pbio.3000410","author":"N Percie du Sert","year":"2020","unstructured":"Percie du Sert, N., Hurst, V., Ahluwalia, A., et al. (2020). The ARRIVE guidelines 2.0: Updated guidelines for reporting animal research. PLoS Biology. https:\/\/doi.org\/10.1371\/journal.pbio.3000410","journal-title":"PLoS Biology"},{"issue":"3","key":"8884_CR34","doi-asserted-by":"publisher","first-page":"105","DOI":"10.1016\/j.blre.2008.10.001","volume":"23","author":"AL Pozo","year":"2009","unstructured":"Pozo, A. L., Godfrey, E. M., & Bowles, K. M. (2009). Splenomegaly: Investigation, diagnosis and management. Blood Reviews, 23(3), 105\u2013111. https:\/\/doi.org\/10.1016\/j.blre.2008.10.001","journal-title":"Blood Reviews"},{"issue":"1","key":"8884_CR35","doi-asserted-by":"publisher","first-page":"144","DOI":"10.1186\/s12974-019-1534-0","volume":"16","author":"LS Robison","year":"2019","unstructured":"Robison, L. S., Popescu, D. L., Anderson, M. E., Francis, N., Hatfield, J., & Sullivan, J. K. (2019). Long-term voluntary wheel running does not alter vascular amyloid burden but reduces neuroinflammation in the Tg-SwDI mouse model of cerebral amyloid angiopathy. Journal of Neuroinflammation, 16(1), 144. https:\/\/doi.org\/10.1186\/s12974-019-1534-0","journal-title":"Journal of Neuroinflammation"},{"issue":"10","key":"8884_CR36","doi-asserted-by":"publisher","DOI":"10.3390\/ijms23105404","volume":"23","author":"R Sanchez-Varo","year":"2022","unstructured":"Sanchez-Varo, R., Mejias-Ortega, M., Fernandez-Valenzuela, J. J., Nu\u00f1ez-Diaz, C., Caceres-Palomo, L., & Vegas-Gomez, L. (2022). Transgenic mouse models of Alzheimer\u2019s disease: An integrative analysis. International Journal of Molecular Sciences, 23(10), Article 5404.","journal-title":"International Journal of Molecular Sciences"},{"issue":"4","key":"8884_CR37","doi-asserted-by":"publisher","first-page":"936","DOI":"10.1523\/JNEUROSCI.1967-16.2016","volume":"37","author":"H Scholtzova","year":"2017","unstructured":"Scholtzova, H., Do, E., Dhakal, S., Sun, Y., Liu, S., Mehta, P. D., et al. (2017). Innate immunity stimulation via toll-like receptor 9 ameliorates vascular amyloid pathology in Tg-SwDI mice with associated cognitive benefits. Journal of Neuroscience, 37(4), 936\u2013959. https:\/\/doi.org\/10.1523\/JNEUROSCI.1967-16.2016","journal-title":"Journal of Neuroscience"},{"issue":"1","key":"8884_CR38","doi-asserted-by":"publisher","DOI":"10.1186\/s12974-018-1380-5","volume":"16","author":"I St-Amour","year":"2019","unstructured":"St-Amour, I., Bosoi, C. R., Par\u00e9, I., Doss, P. M. I. A., Rangachari, M., H\u00e9bert, S. S., Bazin, R., et al. (2019). Peripheral adaptive immunity of the triple transgenic mouse model of Alzheimer\u2019s disease. Journal of Neuroinflammation, 16(1), Article 3. https:\/\/doi.org\/10.1186\/s12974-018-1380-5","journal-title":"Journal of Neuroinflammation"},{"issue":"7","key":"8884_CR39","doi-asserted-by":"publisher","first-page":"1006","DOI":"10.3390\/cells12071006","volume":"12","author":"S Sweetat","year":"2023","unstructured":"Sweetat, S., Nitzan, K., Suissa, N., Haimovich, Y., Lichtenstein, M., Zabit, S., et al. (2023). The beneficial effect of mitochondrial transfer therapy in 5XFAD mice via liver-serum-brain response. Cells, 12(7), 1006. https:\/\/doi.org\/10.3390\/cells12071006","journal-title":"Cells"},{"key":"8884_CR40","doi-asserted-by":"publisher","first-page":"67","DOI":"10.1016\/j.bbi.2020.05.070","volume":"89","author":"MS Unger","year":"2020","unstructured":"Unger, M. S., Li, E., Scharnagl, L., Poupardin, R., Altendorfer, B., Mrowetz, H., et al. (2020). CD8+ T-cells infiltrate Alzheimer\u2019s disease brains and regulate neuronal- and synapse-related gene expression in APP-PS1 transgenic mice. Brain, Behavior, and Immunity, 89, 67\u201386. https:\/\/doi.org\/10.1016\/j.bbi.2020.05.070","journal-title":"Brain, Behavior, and Immunity"},{"key":"8884_CR41","doi-asserted-by":"publisher","first-page":"116","DOI":"10.1016\/j.conb.2020.02.003","volume":"61","author":"DM Walsh","year":"2020","unstructured":"Walsh, D. M., & Selkoe, D. J. (2020). Amyloid \u03b2-protein and beyond: The path forward in Alzheimer\u2019s disease. Current Opinion in Neurobiology, 61, 116\u2013124. https:\/\/doi.org\/10.1016\/j.conb.2020.02.003","journal-title":"Current Opinion in Neurobiology"},{"key":"8884_CR42","doi-asserted-by":"publisher","first-page":"612","DOI":"10.1038\/nrneurol.2017.111","volume":"13","author":"J Wang","year":"2017","unstructured":"Wang, J., Gu, B., & Masters, C. (2017). A systemic view of Alzheimer disease\u2014Insights from amyloid-\u03b2 metabolism beyond the brain. Nature Reviews Neurology, 13, 612\u2013623. https:\/\/doi.org\/10.1038\/nrneurol.2017.111","journal-title":"Nature Reviews Neurology"},{"key":"8884_CR43","doi-asserted-by":"publisher","first-page":"45","DOI":"10.1038\/s41423-020-00558-8","volume":"18","author":"Y Wen","year":"2021","unstructured":"Wen, Y., Lambrecht, J., & Ju, C. (2021). Hepatic macrophages in liver homeostasis and diseases-diversity, plasticity and therapeutic opportunities. Cellular and Molecular Immunology, 18, 45\u201356. https:\/\/doi.org\/10.1038\/s41423-020-00558-8","journal-title":"Cellular and Molecular Immunology"},{"key":"8884_CR44","doi-asserted-by":"publisher","DOI":"10.1016\/j.jneuroim.2024.578332","volume":"390","author":"SK Wyatt-Johnson","year":"2024","unstructured":"Wyatt-Johnson, S. K., Kersey, H. N., & Brutkiewicz, R. R. (2024). Enrichment of liver MAIT cells in a mouse model of Alzheimer\u2019s disease. Journal of Neuroimmunology, 390, Article 578332. https:\/\/doi.org\/10.1016\/j.jneuroim.2024.578332","journal-title":"Journal of Neuroimmunology"},{"issue":"1","key":"8884_CR45","doi-asserted-by":"publisher","first-page":"98","DOI":"10.1016\/j.neuroscience.2007.01.043","volume":"146","author":"F Xu","year":"2007","unstructured":"Xu, F., Grande, A. M., Robinson, J. K., Previti, M. L., Vasek, M., Davis, J., et al. (2007). Early-onset subicular microvascular amyloid and neuroinflammation correlate with behavioral deficits in vasculotropic mutant amyloid beta-protein precursor transgenic mice. Neuroscience, 146(1), 98\u2013107. https:\/\/doi.org\/10.1016\/j.neuroscience.2007.01.043","journal-title":"Neuroscience"},{"issue":"3","key":"8884_CR46","doi-asserted-by":"publisher","first-page":"621","DOI":"10.3233\/JAD-130758","volume":"38","author":"W Xu","year":"2014","unstructured":"Xu, W., Xu, F., Anderson, M. E., Kotarba, A. E., Davis, J., & Robinson, J. K. (2014). Cerebral microvascular rather than parenchymal amyloid-\u03b2 protein pathology promotes early cognitive impairment in transgenic mice. Journal of Alzheimer\u2019s Disease, 38(3), 621\u2013632. https:\/\/doi.org\/10.3233\/JAD-130758","journal-title":"Journal of Alzheimer\u2019s Disease"},{"key":"8884_CR47","doi-asserted-by":"publisher","first-page":"15703","DOI":"10.1038\/srep15703","volume":"5","author":"SH Yang","year":"2015","unstructured":"Yang, S. H., Kim, J., Lee, M. J., & Kim, Y. (2015). Abnormalities of plasma cytokines and spleen in senile APP\/PS1\/Tau transgenic mouse model. Scientific Reports, 5, 15703. https:\/\/doi.org\/10.1038\/srep15703","journal-title":"Scientific Reports"},{"issue":"1","key":"8884_CR48","doi-asserted-by":"publisher","DOI":"10.1111\/acel.13533","volume":"21","author":"ZY Yu","year":"2022","unstructured":"Yu, Z. Y., Chen, D. W., Tan, C. R., Zeng, G. H., He, C. Y., Wang, J., et al. (2022). Physiological clearance of A\u03b2 by spleen and splenectomy aggravates Alzheimer-type pathogenesis. Aging Cell, 21(1), Article e13533. https:\/\/doi.org\/10.1111\/acel.13533","journal-title":"Aging Cell"},{"key":"8884_CR49","doi-asserted-by":"publisher","first-page":"186","DOI":"10.1038\/s41398-020-00878-3","volume":"10","author":"J Zhang","year":"2020","unstructured":"Zhang, J., Ma, L., Chang, L., Pu, Y., Qu, Y., & Hashimoto, K. (2020). A key role of the subdiaphragmatic vagus nerve in the depression-like phenotype and abnormal composition of gut microbiota in mice after lipopolysaccharide administration. Translational Psychiatry, 10, 186. https:\/\/doi.org\/10.1038\/s41398-020-00878-3","journal-title":"Translational Psychiatry"}],"container-title":["NeuroMolecular Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s12017-025-08884-8.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s12017-025-08884-8","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s12017-025-08884-8.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,12,31]],"date-time":"2025-12-31T14:41:38Z","timestamp":1767192098000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s12017-025-08884-8"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,9,4]]},"references-count":49,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2025,12]]}},"alternative-id":["8884"],"URL":"https:\/\/doi.org\/10.1007\/s12017-025-08884-8","relation":{},"ISSN":["1559-1174"],"issn-type":[{"value":"1559-1174","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,9,4]]},"assertion":[{"value":"27 June 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"20 August 2025","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"4 September 2025","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The authors declare no competing interests.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing Interests"}},{"value":"Experiments were conducted following protocols approved by the Animal Care and Use Committee of our University (Protocol ID: 209) and in compliance with NIH guidelines for the use of experimental animals.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethical Approval"}}],"article-number":"61"}}