{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,23]],"date-time":"2026-08-23T17:18:54Z","timestamp":1787505534570,"version":"build-2736575974"},"reference-count":61,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2024,2,14]],"date-time":"2024-02-14T00:00:00Z","timestamp":1707868800000},"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>The complement is a component of the innate immune system designed to fight infections and tissue- or age-related damages. Complement activation creates an inflammatory microenvironment, which enhances cell death. Excessive complement inflammatory activity has been linked to alterations in the structure and functions of the blood\u2013brain barrier, contributing to a poor prognosis for Alzheimer\u2019s disease (AD). In the AD preclinical phase, individuals are often clinically asymptomatic despite evidence of AD neuropathology coupled with heightened inflammation. Considering the involvement of the complement system in the risk of developing AD, we hypothesize that inhibiting complement activation could reduce this inflammatory period observed even before clinical signs, thereby slowing down the onset\/progression of AD. To validate our hypothesis, we injected complement inhibitor factor H into the brain of APP\/PS1 AD mice at early or late stages of this pathology. Our results showed that the injection of factor H had effects on both the onset and progression of AD by reducing proinflammatory IL6, TNF-\u03b1, IL1\u03b2, MAC and amyloid beta levels. This reduction was associated with an increase in VGLUT1 and Psd95 synaptic transmission in the hippocampal region, leading to an improvement in cognitive functions. This study invites a reconsideration of factor H\u2019s therapeutic potential for AD treatment.<\/jats:p>","DOI":"10.3390\/ijms25042272","type":"journal-article","created":{"date-parts":[[2024,2,14]],"date-time":"2024-02-14T06:59:26Z","timestamp":1707893966000},"page":"2272","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Factor H\u2019s Control of Complement Activation Emerges as a Significant and Promising Therapeutic Target for Alzheimer\u2019s Disease Treatment"],"prefix":"10.3390","volume":"25","author":[{"ORCID":"https:\/\/orcid.org\/0009-0003-3014-9041","authenticated-orcid":false,"given":"Iris","family":"Hasantari","sequence":"first","affiliation":[{"name":"INSERM (Institut National de la Sant\u00e9 et de la Recherche M\u00e9dicale), Biologie des Maladies Cardiovasculaires, U1034, University Bordeaux, F-33600 Pessac, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1144-6054","authenticated-orcid":false,"given":"Nabil","family":"Nicolas","sequence":"additional","affiliation":[{"name":"INSERM (Institut National de la Sant\u00e9 et de la Recherche M\u00e9dicale), Biologie des Maladies Cardiovasculaires, U1034, University Bordeaux, F-33600 Pessac, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Philippe","family":"Alzieu","sequence":"additional","affiliation":[{"name":"INSERM (Institut National de la Sant\u00e9 et de la Recherche M\u00e9dicale), Biologie des Maladies Cardiovasculaires, U1034, University Bordeaux, F-33600 Pessac, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-3342-7971","authenticated-orcid":false,"given":"L\u00e9a","family":"Leval","sequence":"additional","affiliation":[{"name":"INSERM (Institut National de la Sant\u00e9 et de la Recherche M\u00e9dicale), Biologie des Maladies Cardiovasculaires, U1034, University Bordeaux, F-33600 Pessac, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andree","family":"Shalabi","sequence":"additional","affiliation":[{"name":"Medizinische Hochschule Hannover, Abt. Infektiologie, 30625 Hannover, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sylvain","family":"Grolleau","sequence":"additional","affiliation":[{"name":"INSERM (Institut National de la Sant\u00e9 et de la Recherche M\u00e9dicale), Biologie des Maladies Cardiovasculaires, U1034, University Bordeaux, F-33600 Pessac, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5458-0253","authenticated-orcid":false,"given":"Virginie","family":"Dinet","sequence":"additional","affiliation":[{"name":"INSERM (Institut National de la Sant\u00e9 et de la Recherche M\u00e9dicale), Biologie des Maladies Cardiovasculaires, U1034, University Bordeaux, F-33600 Pessac, France"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,2,14]]},"reference":[{"key":"ref_1","unstructured":"PubMed (2023, April 28). Alzheimer\u2019s Disease, Available online: https:\/\/pubmed.ncbi.nlm.nih.gov\/20107219\/."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1372","DOI":"10.1016\/j.neurobiolaging.2005.09.012","article-title":"Hippocampal synaptic loss in early Alzheimer\u2019s disease and mild cognitive impairment","volume":"27","author":"Scheff","year":"2006","journal-title":"Neurobiol. Aging"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"103","DOI":"10.3233\/JAD-2005-7203","article-title":"Differential loss of synaptic proteins in Alzheimer\u2019s disease: Implications for synaptic dysfunction","volume":"7","author":"Reddy","year":"2005","journal-title":"J. Alzheimer\u2019s Dis."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"191","DOI":"10.1016\/j.brainres.2009.07.056","article-title":"Disruption of glutamate receptors at Shank-postsynaptic platform in Alzheimer\u2019s disease","volume":"1292","author":"Gong","year":"2009","journal-title":"Brain Res."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"247","DOI":"10.7861\/clinmedicine.16-3-247","article-title":"Drug treatments in Alzheimer\u2019s disease","volume":"16","author":"Briggs","year":"2016","journal-title":"Clin. Med."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"a006387","DOI":"10.1101\/cshperspect.a006387","article-title":"Treatment Strategies Targeting Amyloid \u03b2-Protein","volume":"2","author":"Schenk","year":"2012","journal-title":"Cold Spring Harb. Perspect. Med."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1056\/NEJMoa2212948","article-title":"Lecanemab in Early Alzheimer\u2019s Disease","volume":"388","author":"Swanson","year":"2023","journal-title":"N. Engl. J. Med."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1258","DOI":"10.1002\/cpt.2875","article-title":"Donanemab Population Pharmacokinetics, Amyloid Plaque Reduction, and Safety in Participants with Alzheimer\u2019s Disease","volume":"113","author":"Gueorguieva","year":"2023","journal-title":"Clin. Pharmacol. Ther."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"595","DOI":"10.15252\/emmm.201606210","article-title":"The amyloid hypothesis of Alzheimer\u2019s disease at 25 years","volume":"8","author":"Selkoe","year":"2016","journal-title":"EMBO Mol. Med."},{"key":"ref_10","first-page":"362","article-title":"Hippocampal long-term synaptic depression and memory deficits induced in early amyloidopathy are prevented by enhancing G-protein-gated inwardly rectifying potassium channel activity","volume":"153","author":"Djebari","year":"2019","journal-title":"J. Neurochem."},{"key":"ref_11","first-page":"e53308","article-title":"Intracerebroventricular Injection of Amyloid-\u03b2 Peptides in Normal Mice to Acutely Induce Alzheimer-like Cognitive Deficits","volume":"109","author":"Kim","year":"2016","journal-title":"J. Vis. Exp."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"18008","DOI":"10.1523\/JNEUROSCI.1402-13.2013","article-title":"Changes in Brain Function Occur Years before the Onset of Cognitive Impairment","volume":"33","author":"Goh","year":"2013","journal-title":"J. Neurosci."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"60","DOI":"10.1186\/s13195-017-0283-5","article-title":"On the path to 2025: Understanding the Alzheimer\u2019s disease continuum","volume":"9","author":"Aisen","year":"2017","journal-title":"Alzheimer\u2019s Res. Ther."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"239","DOI":"10.1007\/BF00685397","article-title":"Immunoglobulins and complement factors in senile plaques. An immunoperoxidase study","volume":"57","author":"Eikelenboom","year":"1982","journal-title":"Acta Neuropathol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"195","DOI":"10.1016\/0165-0173(95)00011-9","article-title":"The inflammatory response system of brain: Implications for therapy of Alzheimer and other neurodegenerative diseases","volume":"21","author":"McGeer","year":"1995","journal-title":"Brain Res. Rev."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"853","DOI":"10.3233\/JAD-160488","article-title":"Inflammation, Antiinflammatory Agents, and Alzheimer\u2019s Disease: The Last 22 Years","volume":"54","author":"McGeer","year":"2016","journal-title":"J. Alzheimer\u2019s Dis."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1","DOI":"10.2174\/157015909787602805","article-title":"Implication of Complement System and its Regulators in Alzheimers Disease","volume":"7","author":"Kolev","year":"2009","journal-title":"Curr. Neuropharmacol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"927","DOI":"10.1016\/S0002-9440(10)65340-0","article-title":"Up-Regulated Production and Activation of the Complement System in Alzheimer\u2019s Disease Brain","volume":"154","author":"Yasojima","year":"1999","journal-title":"Am. J. Pathol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"412","DOI":"10.1038\/s41588-022-01024-z","article-title":"New Insights on the Genetic Etiology of Alzheimer\u2019s and Related Dementia","volume":"54","author":"Bellenguez","year":"2020","journal-title":"Nat. Genet."},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Torvell, M., Carpanini, S.M., Daskoulidou, N., Byrne, R.A.J., Sims, R., and Morgan, B.P. (2021). Genetic Insights into the Impact of Complement in Alzheimer\u2019s Disease. Genes, 12.","DOI":"10.3390\/genes12121990"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1034","DOI":"10.1038\/npp.2015.232","article-title":"CFH Variants Affect Structural and Functional Brain Changes and Genetic Risk of Alzheimer\u2019s Disease","volume":"41","author":"Zhang","year":"2015","journal-title":"Neuropsychopharmacology"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"720","DOI":"10.1002\/ajmg.b.30668","article-title":"Association of complement factor H Y402H gene polymorphism with Alzheimer\u2019s disease","volume":"147B","author":"Zetterberg","year":"2008","journal-title":"Am. J. Med. Genet. Part B Neuropsychiatr. Genet."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"165","DOI":"10.1016\/j.neurobiolaging.2008.03.003","article-title":"Association study of the CFH Y402H polymorphism with Alzheimer\u2019s disease","volume":"31","author":"Laumet","year":"2010","journal-title":"Neurobiol. Aging"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"13873","DOI":"10.1038\/s41598-019-50420-9","article-title":"CFH exerts anti-oxidant effects on retinal pigment epithelial cells independently from protecting against membrane attack complex","volume":"9","author":"Borras","year":"2019","journal-title":"Sci. Rep."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"443","DOI":"10.3389\/fimmu.2020.00443","article-title":"Mechanisms of FH Protection Against Neovascular AMD","volume":"11","author":"Borras","year":"2020","journal-title":"Front. Immunol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"2111","DOI":"10.1016\/j.celrep.2019.07.060","article-title":"Complement C3 Is Activated in Human AD Brain and Is Required for Neurodegeneration in Mouse Models of Amyloidosis and Tauopathy","volume":"28","author":"Wu","year":"2019","journal-title":"Cell Rep."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"eaaf6295","DOI":"10.1126\/scitranslmed.aaf6295","article-title":"Complement C3 deficiency protects against neurodegeneration in aged plaque-rich APP\/PS1 mice","volume":"9","author":"Shi","year":"2017","journal-title":"Sci. Transl. Med."},{"key":"ref_28","first-page":"116","article-title":"Complement protein C5a enhances the \u03b2-amyloid-induced neuro-inflammatory response in microglia in Alzheimer\u2019s disease","volume":"34","author":"An","year":"2018","journal-title":"Med. Sci."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"124","DOI":"10.1016\/S0165-5728(99)00261-1","article-title":"The role of complement anaphylatoxin C5a in neurodegeneration: Implications in Alzheimer\u2019s disease","volume":"105","author":"Mukherjee","year":"2000","journal-title":"J. Neuroimmunol."},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Panayiotou, E., Fella, E., Andreou, S., Papacharalambous, R., Gerasimou, P., Costeas, P., Angeli, S., Kousiappa, I., Papacostas, S., and Kyriakides, T. (2019). C5aR agonist enhances phagocytosis of fibrillar and non-fibrillar A\u03b2 amyloid and preserves memory in a mouse model of familial Alzheimer\u2019s disease. PLoS ONE, 14.","DOI":"10.1371\/journal.pone.0225417"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"645","DOI":"10.3233\/JAD-160572","article-title":"A\u03b2PP\/PS1 Transgenic Mice Show Sex Differences in the Cerebellum Associated with Aging","volume":"54","author":"Herrera","year":"2016","journal-title":"J. Alzheimer\u2019s Dis."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"318","DOI":"10.1016\/j.nbd.2003.08.009","article-title":"Gender differences in the amount and deposition of amyloid\u03b2 in APPswe and PS1 double transgenic mice","volume":"14","author":"Wang","year":"2003","journal-title":"Neurobiol. Dis."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"311","DOI":"10.1161\/01.STR.18.2.311","article-title":"Cerebral amyloid angiopathy. A critical review","volume":"18","author":"Vinters","year":"1987","journal-title":"Stroke"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"124","DOI":"10.1136\/jnnp-2011-301308","article-title":"Sporadic cerebral amyloid angiopathy revisited: Recent insights into pathophysiology and clinical spectrum","volume":"83","author":"Charidimou","year":"2011","journal-title":"J. Neurol. Neurosurg. Psychiatry"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1038\/nrneurol.2012.236","article-title":"Deciphering the mechanism underlying late-onset Alzheimer disease","volume":"9","author":"Krstic","year":"2012","journal-title":"Nat. Rev. Neurol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"233","DOI":"10.3233\/JAD-122131","article-title":"\u03b2CTF-Correlated Burst of Hippocampal TNF\u03b1 Occurs at a Very Early, Pre-Plaque Stage in the TgCRND8 Mouse Model of Alzheimer\u2019s Disease","volume":"36","author":"Cavanagh","year":"2013","journal-title":"J. Alzheimer\u2019s Dis."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1016\/j.neurobiolaging.2016.07.009","article-title":"Inhibiting tumor necrosis factor-\u03b1 before amyloidosis prevents synaptic deficits in an Alzheimer\u2019s disease model","volume":"47","author":"Cavanagh","year":"2016","journal-title":"Neurobiol. Aging"},{"key":"ref_38","doi-asserted-by":"crossref","unstructured":"Dinet, V., Arouche-Delaperche, L., D\u00e9gardin, J., Naud, M.-C., Picaud, S., and Krantic, S. (2022). Concomitant Retinal Alterations in Neuronal Activity and TNF\u03b1 Pathway Are Detectable during the Pre-Symptomatic Stage in a Mouse Model of Alzheimer\u2019s Disease. Cells, 11.","DOI":"10.3390\/cells11101650"},{"key":"ref_39","first-page":"5696241","article-title":"Expression of Phenotypic Astrocyte Marker Is Increased in a Transgenic Mouse Model of Alzheimer\u2019s Disease versus Age-Matched Controls: A Presymptomatic Stage Study","volume":"2016","author":"Cavanagh","year":"2016","journal-title":"Int. J. Alzheimer\u2019s Dis."},{"key":"ref_40","first-page":"412","article-title":"Targeting Tumor Necrosis Factor Alpha for Alzheimer\u2019s Disease","volume":"13","author":"Decourt","year":"2016","journal-title":"Curr. Alzheimer Res."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"354","DOI":"10.1016\/j.jhep.2014.08.050","article-title":"C5aR, TNF-\u03b1, and FGL2 contribute to coagulation and complement activation in virus-induced fulminant hepatitis","volume":"62","author":"Liu","year":"2015","journal-title":"J. Hepatol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"128","DOI":"10.1016\/0169-328X(92)90202-M","article-title":"Expression of amyloid precursor protein mRNAs in endothelial, neuronal and glial cells: Modulation by interleukin-1","volume":"16","author":"Forloni","year":"1992","journal-title":"Mol. Brain Res."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"1605","DOI":"10.1523\/JNEUROSCI.23-05-01605.2003","article-title":"Interleukin-1 Mediates Pathological Effects of Microglia on Tau Phosphorylation and on Synaptophysin Synthesis in Cortical Neurons through a p38-MAPK Pathway","volume":"23","author":"Li","year":"2003","journal-title":"J. Neurosci."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"6539","DOI":"10.4049\/jimmunol.1100620","article-title":"Blocking IL-1 Signaling Rescues Cognition, Attenuates Tau Pathology, and Restores Neuronal \u03b2-Catenin Pathway Function in an Alzheimer\u2019s Disease Model","volume":"187","author":"Kitazawa","year":"2011","journal-title":"J. Immunol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"544","DOI":"10.1007\/BF00571510","article-title":"Interleukin-6 is present in early stages of plaque formation and is restricted to the brains of Alzheimer\u2019s disease patients","volume":"89","author":"Huell","year":"1995","journal-title":"Acta Neuropathol."},{"key":"ref_46","doi-asserted-by":"crossref","unstructured":"Walsh, K.P., Minamide, L.S., Kane, S.J., Shaw, A.E., Brown, D.R., Pulford, B., Zabel, M.D., Lambeth, J.D., Kuhn, T.B., and Bamburg, J.R. (2014). Amyloid-\u03b2 and Proinflammatory Cytokines Utilize a Prion Protein-Dependent Pathway to Activate NADPH Oxidase and Induce Cofilin-Actin Rods in Hippocampal Neurons. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0095995"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"1500","DOI":"10.1073\/pnas.94.4.1500","article-title":"Progressive decline in avoidance learning paralleled by inflammatory neurodegeneration in transgenic mice expressing interleukin 6 in the brain","volume":"94","author":"Heyser","year":"1997","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"251","DOI":"10.1038\/s41398-021-01349-z","article-title":"Pro-inflammatory interleukin-6 signaling links cognitive impairments and peripheral metabolic alterations in Alzheimer\u2019s disease","volume":"11","author":"Pascoal","year":"2021","journal-title":"Transl. Psychiatry"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"930","DOI":"10.1016\/j.biopsych.2010.06.012","article-title":"A Meta-Analysis of Cytokines in Alzheimer\u2019s Disease","volume":"68","author":"Swardfager","year":"2010","journal-title":"Biol. Psychiatry"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"572","DOI":"10.1002\/ana.410300410","article-title":"Physical basis of cognitive alterations in alzheimer\u2019s disease: Synapse loss is the major correlate of cognitive impairment","volume":"30","author":"Terry","year":"1991","journal-title":"Ann. Neurol."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"450","DOI":"10.1177\/1533317511421780","article-title":"Brain Glutamate Levels Are Decreased in Alzheimer\u2019s Disease","volume":"26","author":"Fayed","year":"2011","journal-title":"Am. J. Alzheimer\u2019s Dis. Other Dementiasr"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"386","DOI":"10.1002\/cne.20250","article-title":"Vesicular glutamate transporter 3 expression identifies glutamatergic amacrine cells in the rodent retina","volume":"477","author":"Johnson","year":"2004","journal-title":"J. Comp. Neurol."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"1619","DOI":"10.1016\/j.neurobiolaging.2007.04.010","article-title":"Loss of VGLUT1 and VGLUT2 in the prefrontal cortex is correlated with cognitive decline in Alzheimer disease","volume":"29","author":"Kashani","year":"2008","journal-title":"Neurobiol. Aging"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"1303","DOI":"10.1002\/hipo.22607","article-title":"Down-regulation of glutamatergic terminals (VGLUT1) driven by A\u03b2 in Alzheimer\u2019s disease","volume":"26","author":"Tordera","year":"2016","journal-title":"Hippocampus"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"963","DOI":"10.3233\/JAD-150659","article-title":"JNK: A Putative Link between Insulin Signaling and VGLUT1 in Alzheimer\u2019s Disease","volume":"50","author":"Solas","year":"2016","journal-title":"J. Alzheimer\u2019s Dis."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"795","DOI":"10.3233\/JAD-2010-100090","article-title":"Reduction in Post-Synaptic Scaffolding PSD-95 and SAP-102 Protein Levels in the Alzheimer Inferior Temporal Cortex is Correlated with Disease Pathology","volume":"21","author":"Proctor","year":"2010","journal-title":"J. Alzheimer\u2019s Dis."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"13029","DOI":"10.1523\/JNEUROSCI.1698-15.2015","article-title":"ComplementC3-Deficient Mice Fail to Display Age-Related Hippocampal Decline","volume":"35","author":"Shi","year":"2015","journal-title":"J. Neurosci."},{"key":"ref_58","first-page":"4039","article-title":"Complement factor H\u2013deficient mice develop spontaneous hepatic tumors","volume":"130","author":"Laskowski","year":"2020","journal-title":"J. Clin. Investig."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"437","DOI":"10.31887\/DCNS.2016.18.4\/cepperson","article-title":"Considering sex and gender in Alzheimer disease and other dementias","volume":"18","author":"Podcasy","year":"2016","journal-title":"Dialog. Clin. Neurosci."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"1789","DOI":"10.1016\/j.cell.2016.05.007","article-title":"Mapping of Brain Activity by Automated Volume Analysis of Immediate Early Genes","volume":"165","author":"Renier","year":"2016","journal-title":"Cell"},{"key":"ref_61","doi-asserted-by":"crossref","unstructured":"Nicolas, N., and Roux, E. (2021). 3D Imaging and Quantitative Characterization of Mouse Capillary Coronary Network Architecture. Biology, 10.","DOI":"10.3390\/biology10040306"}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/25\/4\/2272\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T13:59:40Z","timestamp":1760104780000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/25\/4\/2272"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,2,14]]},"references-count":61,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2024,2]]}},"alternative-id":["ijms25042272"],"URL":"https:\/\/doi.org\/10.3390\/ijms25042272","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,2,14]]}}}