{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,7]],"date-time":"2026-07-07T14:19:05Z","timestamp":1783433945409,"version":"3.54.6"},"reference-count":93,"publisher":"MDPI AG","issue":"13","license":[{"start":{"date-parts":[[2026,6,28]],"date-time":"2026-06-28T00:00:00Z","timestamp":1782604800000},"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>Exploration of the gene-level changes that occur during post-ischemic neurodegeneration in the frontal cortex is crucial for understanding the development of dementia. An ischemic model of Alzheimer\u2019s disease was used to evaluate changes in the expression of the receptor for advanced glycation end products (RAGE) and low-density lipoprotein receptor-related protein 1 (LRP1), which are associated with amyloid and tau protein, in the frontal cortex after 10 min of cerebral ischemia, with survival at 2, 7, and 30 days and 0.5, 1, 1.5, and 2 years. LRP1 and RAGE expression was assessed by reverse transcription-quantitative polymerase chain reaction. After two days and 1.5 and 2 years post-ischemia, LRP1 expression was increased, after 7 days and 0.5 years it was decreased, and after 30 days and 1 year it oscillated around control values. The decrease in RAGE expression was statistically significant compared to the control group after 2 and 7 days and after 0.5 years, and after 30 days it oscillated around the control value, while after 1\u20132 years it increased significantly. RAGE and LRP1 expression showed the same pattern of changes from day 7 to year 2, peaking at 1 and 1.5 years, respectively. Another peak of RAGE overexpression was noted 2 years after ischemia. After 1, 1.5 and 2 years, overexpression of RAGE and LRP1 was observed after ischemia, with the dynamics of LRP1 changes being lower. Overall, the data showed a predominance of RAGE expression over LRP1 expression at 1-, 1.5-, and 2-years post-ischemia. The modification of LRP1 and RAGE after ischemia is useful in studying the molecular ischemic pathways involved in the development of Alzheimer\u2019s disease.<\/jats:p>","DOI":"10.3390\/ijms27135831","type":"journal-article","created":{"date-parts":[[2026,6,30]],"date-time":"2026-06-30T00:55:11Z","timestamp":1782780911000},"page":"5831","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["LRP1 and RAGE Expression in the Frontal Cortex in the Alzheimer\u2019s Disease Ischemia Model During 2 Years of Follow-Up"],"prefix":"10.3390","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0764-1356","authenticated-orcid":false,"given":"Ryszard","family":"Pluta","sequence":"first","affiliation":[{"name":"Department of Pathophysiology, Medical University of Lublin, 20-090 Lublin, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marzena","family":"U\u0142amek-Kozio\u0142","sequence":"additional","affiliation":[{"name":"Department of Neurology, Institute of Psychiatry and Neurology, 02-957 Warsaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Janusz","family":"Kocki","sequence":"additional","affiliation":[{"name":"Department of Clinical Genetics, Medical University of Lublin, 20-080 Lublin, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna","family":"Bogucka-Kocka","sequence":"additional","affiliation":[{"name":"Department of Biology and Genetics, Medical University of Lublin, 20-093 Lublin, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2879-9945","authenticated-orcid":false,"given":"Stanis\u0142aw J.","family":"Czuczwar","sequence":"additional","affiliation":[{"name":"Department of Pathophysiology, Medical University of Lublin, 20-090 Lublin, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jacek","family":"Bogucki","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, John Paul II Catholic University of Lublin, 20-708 Lublin, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,6,28]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"110543","DOI":"10.1016\/j.biopha.2020.110543","article-title":"The effect of crocin on memory, hippocampal acetylcholine level, and apoptosis in a rat model of cerebral ischemia","volume":"130","author":"Yuan","year":"2020","journal-title":"Biomed. Pharmacother."},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Lecordier, S., Pons, V., Rivest, S., and ElAli, A. (2022). Multifocal Cerebral Microinfarcts Modulate Early Alzheimer\u2019s Disease Pathology in a Sex-Dependent Manner. Front. Immunol., 12.","DOI":"10.3389\/fimmu.2021.813536"},{"key":"ref_3","first-page":"849","article-title":"Effects of curcumin on memory, hippocampal acetylcholine level and neuroapoptosis in repeated cerebral ischemia rat model","volume":"36","author":"Li","year":"2023","journal-title":"Pak. J. Pharm. Sci."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"166","DOI":"10.2174\/0115672050320921240627050736","article-title":"A Look at the Etiology of Alzheimer\u2019s Disease based on the Brain Ischemia Model","volume":"21","author":"Pluta","year":"2024","journal-title":"Curr. Alzheimer Res."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1431","DOI":"10.2147\/IJN.S452045","article-title":"Nasal Administration of bFGF-Loaded Nanoliposomes Attenuates Neuronal Injury and Cognitive Deficits in Mice with Vascular Dementia Induced by Repeated Cerebral Ischemia-Reperfusion","volume":"19","author":"Zhang","year":"2024","journal-title":"Int. J. Nanomed."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"115598","DOI":"10.1016\/j.expneurol.2025.115598","article-title":"A new microinfarcts model produces widespread bilateral infarcts and persistent cognitive deficits in middle-aged mice","volume":"397","author":"Liu","year":"2026","journal-title":"Exp. Neurol."},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Pluta, R., and U\u0142amek-Kozio\u0142, M. (2026). Genomic and proteomic conversion of brain ischemia to Alzheimer\u2019s disease. Front. Cell Dev. Biol., 14.","DOI":"10.3389\/fcell.2026.1804251"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1551","DOI":"10.1161\/01.STR.0000169933.88903.cf","article-title":"Transformation of diffuse beta-amyloid precursor protein and beta-amyloid deposits to plaques in the thalamus after transient occlusion of the middle cerebral artery in rats","volume":"36","author":"Puurunen","year":"2005","journal-title":"Stroke"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1863","DOI":"10.1002\/ar.21018","article-title":"Alzheimer\u2019s mechanisms in ischemic brain degeneration","volume":"292","author":"Pluta","year":"2009","journal-title":"Anat. Rec."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"473","DOI":"10.1016\/j.bbadis.2006.10.011","article-title":"Cdk5 is involved in NFT-like tauopathy induced by transient cerebral ischemia in female rats","volume":"1772","author":"Wen","year":"2007","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1987","DOI":"10.1111\/ejn.13277","article-title":"Early glycogen synthase kinase-3beta and protein phosphatase 2A independent tau dephosphorylation during global brain ischaemia and reperfusion following cardiac arrest and the role of the adenosine monophosphate kinase pathway","volume":"44","author":"Majd","year":"2016","journal-title":"Eur. J. Neurosci."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"2441","DOI":"10.1177\/0271678X16668889","article-title":"Modifications of tau protein after cerebral ischemia and reperfusion in rats are similar to those occurring in Alzheimer\u2019s disease\u2014Hyperphosphorylation and cleavage of 4- and 3-repeat tau","volume":"37","author":"Fujii","year":"2017","journal-title":"J. Cereb. Blood Flow Metab."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"134","DOI":"10.1016\/j.neuint.2018.04.004","article-title":"Tau pathology and neurochemical changes associated with memory dysfunction in an optimised murine model of global cerebral ischaemia\u2014A potential model for vascular dementia?","volume":"118","author":"Khan","year":"2018","journal-title":"Neurochem. Int."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1","DOI":"10.24976\/Discov.Med.202537192.1","article-title":"Neuroinflammation in the Post-Ischemic Brain in the Presence of Amyloid and Tau Protein","volume":"37","author":"Pluta","year":"2025","journal-title":"Discov. Med."},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Pluta, R. (2025). Direct and indirect role of non-coding RNAs in company with amyloid and tau protein in promoting neuroinflammation in post-ischemic brain neurodegeneration. Front. Cell. Neurosci., 19.","DOI":"10.3389\/fncel.2025.1670462"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"10739","DOI":"10.3390\/ijms241310739","article-title":"Post-Ischemic Permeability of the Blood-Brain Barrier to Amyloid and Platelets as a Factor in the Maturation of Alzheimer\u2019s Disease-Type Brain Neurodegeneration","volume":"24","author":"Pluta","year":"2023","journal-title":"Int. J. Mol. Sci."},{"key":"ref_17","first-page":"S113","article-title":"One year follow up in ischemic brain injury and the role of Alzheimer factors","volume":"60","author":"Maciejewski","year":"2011","journal-title":"Physiol. Res."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"227","DOI":"10.1016\/j.bbr.2011.01.009","article-title":"Impaired conditioned emotional response and object recognition are concomitant to neuronal damage in the amygdale and perirhinal cortex in middle-aged ischemic rats","volume":"219","author":"Plamondon","year":"2011","journal-title":"Behav. Brain Res."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.bbr.2010.12.004","article-title":"Transient brain ischemia due to cardiac arrest causes irreversible long-lasting cognitive injury","volume":"219","author":"Kiryk","year":"2011","journal-title":"Behav. Brain Res."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"86","DOI":"10.1016\/j.lfs.2011.04.024","article-title":"Cerebral ischemia aggravates cognitive impairment in a rat model of Alzheimer\u2019s disease","volume":"89","author":"Li","year":"2011","journal-title":"Life Sci."},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Cohan, C.H., Neumann, J.T., Dave, K.R., Alekseyenko, A., Binkert, M., Stransky, K., Lin, H.W., Barnes, C.A., Wright, C.B., and Perez-Pinzon, M.A. (2015). Effect of cardiac arrest on cognitive impairment and hippocampal plasticity in middle-aged rats. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0124918"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"39","DOI":"10.3233\/JAD-190764","article-title":"Vascular Risk Factors and Alzheimer\u2019s Disease: Blood-Brain Barrier Disruption, Metabolic Syndromes, and Molecular Links","volume":"73","author":"He","year":"2020","journal-title":"J. Alzheimer\u2019s Dis."},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Neyra Chauca, J.M., and Robles Martinez, G.G. (2025). Histological and Functional Breakdown of the Blood\u2212Brain Barrier in Alzheimer\u2019s Disease: A Multifactorial Intersection. Neurol. Int., 17.","DOI":"10.20944\/preprints202507.1527.v1"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"276","DOI":"10.1038\/s41593-020-00764-7","article-title":"Molecular characterization of selectively vulnerable neurons in Alzheimer\u2019s disease","volume":"24","author":"Leng","year":"2021","journal-title":"Nat. Neurosci."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"858","DOI":"10.1038\/s41586-024-07606-7","article-title":"Single-cell multi region dissection of Alzheimer\u2019s disease","volume":"632","author":"Mathys","year":"2024","journal-title":"Nature"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1492","DOI":"10.3390\/ijms27031492","article-title":"Altered Microglia-Neuron Crosstalk and Regional Heterogeneity in Alzheimer\u2019s Disease Revealed by Single-Nucleus RNA Sequencing","volume":"27","author":"Yang","year":"2026","journal-title":"Int. J. Mol. Sci."},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Carapeto, A.P., Marcuello, C., Fa\u00edsca, P.F.N., and Rodrigues, M.S. (2024). Morphological and Biophysical Study of S100A9 Protein Fibrils by Atomic Force Microscopy Imaging and Nanomechanical Analysis. Biomolecules, 14.","DOI":"10.3390\/biom14091091"},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Ziaunys, M., Sakalauskas, A., Mikalauskaite, K., and Smirnovas, V. (2021). Polymorphism of Alpha-Synuclein Amyloid Fibrils Depends on Ionic Strength and Protein Concentration. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms222212382"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1816","DOI":"10.17305\/bb.2024.10820","article-title":"Brain regions differences in amyloid-\u03b2 and gene expression in early APP\/PS1 mice and identification of Npas4 as a key molecule in Alzheimer\u2019s disease","volume":"24","author":"Wang","year":"2024","journal-title":"Biomol. Biomed."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"271","DOI":"10.1016\/0197-4580(95)00021-6","article-title":"Staging of Alzheimer\u2019s disease-related neurofibrillary changes","volume":"16","author":"Braak","year":"1996","journal-title":"Neurobiol. Aging"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"984","DOI":"10.1212\/WNL.0000000000001935","article-title":"Temporal course and pathologic basis of unawareness of memory loss in dementia","volume":"85","author":"Wilson","year":"2015","journal-title":"Neurology"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1305","DOI":"10.1016\/j.jalz.2018.07.219","article-title":"The Reserve, Resilience and Protective Factors PIA Empirical Definitions and Conceptual Frameworks Workgroup. Whitepaper: Defining and investigating cognitive reserve, brain reserve, and brain maintenance","volume":"16","author":"Stern","year":"2020","journal-title":"Alzheimer\u2019s Dement."},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Ramanathan, A., Nelson, A.R., Sagare, A.P., and Zlokovic, B.V. (2015). Impaired vascular-mediated clearance of brain amyloid beta in Alzheimer\u2019s disease: The role, regulation and restoration of LRP1. Front. Aging Neurosci., 7.","DOI":"10.3389\/fnagi.2015.00136"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1267","DOI":"10.1194\/jlr.R075796","article-title":"Role of LRP1 in the pathogenesis of Alzheimer\u2019s disease: Evidence from clinical and preclinical studies","volume":"58","author":"Shinohara","year":"2017","journal-title":"J. Lipid. Res."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"177830","DOI":"10.1016\/j.ejphar.2025.177830","article-title":"LRP1 at the crossroads of Parkinson\u2019s and Alzheimer\u2019s: Divergent roles in \u03b1-synuclein and amyloid pathology","volume":"1002","author":"Alshahrani","year":"2025","journal-title":"Eur. J. Pharmacol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"3574","DOI":"10.4103\/NRR.NRR-D-24-00865","article-title":"Systematic review of amyloid-beta clearance proteins from the brain to the periphery: Implications for Alzheimer\u2019s disease diagnosis and therapeutic targets","volume":"20","author":"Huang","year":"2025","journal-title":"Neural. Regen. Res."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"103390","DOI":"10.1016\/j.mcn.2019.103390","article-title":"Amyloid-beta impairs insulin signaling by accelerating autophagy-lysosomal degradation of LRP-1 and IR-\u03b2 in blood-brain barrier endothelial cells in vitro and in 3XTg-AD mice","volume":"99","author":"Gali","year":"2019","journal-title":"Mol. Cell. Neurosci."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"100715","DOI":"10.1016\/j.jbc.2021.100715","article-title":"Regulation of tau internalization, degradation, and seeding by LRP1 reveals multiple pathways for tau catabolism","volume":"296","author":"Cooper","year":"2021","journal-title":"J. Biol. Chem."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"381","DOI":"10.1038\/s41586-020-2156-5","article-title":"LRP1 is a master regulator of tau uptake and spread","volume":"580","author":"Rauch","year":"2020","journal-title":"Nature"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"483","DOI":"10.1007\/s10571-015-0233-3","article-title":"Role of RAGE in Alzheimer\u2019s disease","volume":"36","author":"Cai","year":"2016","journal-title":"Cell Mol. Neurobiol."},{"key":"ref_41","doi-asserted-by":"crossref","unstructured":"Li, W., Chen, Q., Peng, C., Yang, D., Liu, S., Lv, Y., Jiang, L., Xu, S., and Huang, L. (2025). Roles of the Receptor for Advanced Glycation End Products and Its Ligands in the Pathogenesis of Alzheimer\u2019s Disease. Int. J. Mol. Sci., 26.","DOI":"10.3390\/ijms26010403"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"12251","DOI":"10.18632\/aging.103411","article-title":"Heterogeneity in brain distribution of activated microglia and astrocytes in a rat ischemic model of Alzheimer\u2019s disease after 2 years of survival","volume":"12","author":"Radenovic","year":"2020","journal-title":"Aging"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"442","DOI":"10.2174\/0115672050385480250619045022","article-title":"Alterations of Mitophagy (BNIP3), Apoptosis (CASP3), and Autophagy (BECN1) Genes in the Frontal Cortex in an Ischemic Model of Alzheimer\u2019s Disease with Long-Term Survival","volume":"22","author":"Pluta","year":"2025","journal-title":"Curr. Alzheimer Res."},{"key":"ref_44","doi-asserted-by":"crossref","unstructured":"Pluta, R., U\u0142amek-Kozio\u0142, M., Kocki, J., Bogucka-Kocka, A., Bogucki, J., and Czuczwar, S.J. (2026). Alterations of Apolipoprotein A1, E, and J Genes in the Frontal Cortex in an Ischemic Model of Alzheimer\u2019s Disease with 2-Year Survival. Int. J. Mol. Sci., 27.","DOI":"10.3390\/ijms27135831"},{"key":"ref_45","doi-asserted-by":"crossref","unstructured":"Pluta, R., Bogucka-Kocka, A., Kocki, J., Bogucki, J., and Czuczwar, S.J. (2026). Tau Protein, \u03b1-synuclein, and Amyloid Precursor Protein Processing Genes in the Frontal Cortex of an Ischemic Alzheimer\u2019s Disease Model. Curr. Alzheimer Res., in press.","DOI":"10.2174\/0115672050403689251103120712"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"411","DOI":"10.3233\/JAD-160542","article-title":"Tau proteins cross the blood-brain barrier","volume":"55","author":"Banks","year":"2017","journal-title":"J. Alzheimer\u2019s Dis."},{"key":"ref_47","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_48","doi-asserted-by":"crossref","first-page":"1508","DOI":"10.1007\/s11064-012-0778-1","article-title":"Modulation of RAGE isoforms expression in the brain and plasma of rats exposed to transient focal cerebral ischemia","volume":"37","author":"Greco","year":"2012","journal-title":"Neurochem. Res."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"167","DOI":"10.1016\/S0006-8993(02)04149-5","article-title":"RAGE is expressed in pyramidal cells of the hippocampus following moderate hypoxic-ischemic brain injury in rats","volume":"966","author":"Ma","year":"2003","journal-title":"Brain Res."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"1553","DOI":"10.1007\/s11064-014-1345-8","article-title":"Effect of transient cerebral ischemia on the expression of receptor for advanced glycation end products (RAGE) in the gerbil hippocampus proper","volume":"39","author":"Lee","year":"2014","journal-title":"Neurochem. Res."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"e532","DOI":"10.1002\/ctm2.532","article-title":"PNS protects brain against ischemic injury by acting as an antagonist for AGE\/RAGE signaling","volume":"11","author":"Wang","year":"2021","journal-title":"Clin. Transl. Med."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"36330","DOI":"10.1074\/jbc.M706407200","article-title":"Hypoxia-inducible factor-1 mediates neuronal expression of the receptor for advanced glycation end products following hypoxia\/ischemia","volume":"282","author":"Pichiule","year":"2007","journal-title":"J. Biol. Chem."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"302","DOI":"10.1016\/j.jocn.2007.12.011","article-title":"Neuronal RAGE expression modulates severity of injury following transient focal cerebral ischemia","volume":"16","author":"Hassid","year":"2009","journal-title":"J. Clin. Neurosci."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"12023","DOI":"10.1523\/JNEUROSCI.2435-08.2008","article-title":"The HMGB1 receptor RAGE mediates ischemic brain damage","volume":"28","author":"Muhammad","year":"2008","journal-title":"J. Neurosci."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"8749","DOI":"10.1523\/JNEUROSCI.0141-14.2014","article-title":"RAGE inhibition in microglia prevents ischemia-dependent synaptic dysfunction in an amyloid-enriched environment","volume":"34","author":"Origlia","year":"2014","journal-title":"J. Neurosci."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"685","DOI":"10.1038\/382685a0","article-title":"RAGE and amyloid-\u03b2 peptide neurotoxicity in Alzheimer\u2019s disease","volume":"382","author":"Yan","year":"1996","journal-title":"Nature"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"907","DOI":"10.1038\/nm890","article-title":"RAGE mediates amyloid-\u03b2 peptide transport across the blood-brain barrier and accumulation in brain","volume":"9","author":"Deane","year":"2003","journal-title":"Nat. Med."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"1043","DOI":"10.1096\/fj.09-139634","article-title":"RAGE dependent signalling in microglia contributes to neuroinflammation, A\u03b2 accumulation, and impaired learning\/memory in a mouse model of Alzheimer\u2019s disease","volume":"24","author":"Fang","year":"2010","journal-title":"FASEB J."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"240","DOI":"10.2741\/s265","article-title":"RAGE is a key cellular target for Abeta-induced perturbation in Alzheimer\u2019s disease","volume":"4","author":"Yan","year":"2012","journal-title":"Front. Biosci."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1006\/exnr.2001.7732","article-title":"Involvement of microglial receptor for advanced glycation endproducts (RAGE) in Alzheimer\u2019s disease: Identification of a cellular activation mechanism","volume":"171","author":"Lue","year":"2001","journal-title":"Exp. Neurol."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"256","DOI":"10.1016\/S0006-8993(00)03075-4","article-title":"Immunohistochemical distribution of the receptor for advanced glycation end products in neurons and astrocytes in Alzheimer\u2019s disease","volume":"888","author":"Sasaki","year":"2001","journal-title":"Brain Res."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"428","DOI":"10.2174\/1567205018666210906092940","article-title":"Effect of High Cholesterol Regulation of LRP1 and RAGE on A\u03b2 Transport Across the Blood-Brain Barrier in Alzheimer\u2019s Disease","volume":"18","author":"Zhou","year":"2021","journal-title":"Curr. Alzheimer Res."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"620","DOI":"10.1002\/ana.410230617","article-title":"Neurofibrillary tangle formation in the nucleus basalis of Meynert ipsilateral to a massive cerebral infarct","volume":"23","author":"Kato","year":"1988","journal-title":"Ann. Neurol."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"22684","DOI":"10.1074\/jbc.M311768200","article-title":"Transient cerebral ischemia induces aberrant neuronal cell cycle re-entry and Alzheimer\u2019s disease-like tauopathy in female rats","volume":"279","author":"Wen","year":"2004","journal-title":"J. Biol. Chem."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1186\/s40478-019-0700-z","article-title":"Tau and TDP-43 accumulation of the basal nucleus of Meynert in individuals with cerebral lobar infarcts or hemorrhage","volume":"7","author":"Hatsuta","year":"2019","journal-title":"Acta Neuropathol. Commun."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"1281","DOI":"10.1007\/s12035-019-01799-z","article-title":"Expression of the tau protein and amyloid protein precursor processing genes in the CA3 area of the hippocampus in the ischemic model of Alzheimer\u2019s disease in the rat","volume":"57","author":"Pluta","year":"2020","journal-title":"Mol. Neurobiol."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"94","DOI":"10.1007\/s12017-022-08731-0","article-title":"Tau and GSK-3 are Critical Contributors to \u03b1-Synuclein-Mediated Post-Stroke Brain Damage","volume":"25","author":"Mehta","year":"2023","journal-title":"Neuromolecular Med."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"e62","DOI":"10.1212\/WNL.0000000000201344","article-title":"In Vivo Detection of Neurofibrillary Tangles by 18F-MK-6240 PET\/MR in Patients with Ischemic Stroke","volume":"100","author":"Michiels","year":"2023","journal-title":"Neurology"},{"key":"ref_69","doi-asserted-by":"crossref","unstructured":"Parvatikar, P.P., Patil, S.M., Patil, B.S., Reddy, R.C., Bagoji, I., Kotennavar, M.S., Patil, S., Patil, A.V., Das, K.K., and Das, S.N. (2023). Effect of Mucuna pruriens on brain NMDA receptor and tau protein gene expression in cerebral ischemic rats. Front. Physiol., 14.","DOI":"10.3389\/fphys.2023.1092032"},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"829","DOI":"10.1016\/j.biopsych.2022.10.015","article-title":"Pathogenic Role of RAGE in Tau Transmission and Memory Deficits","volume":"93","author":"Kim","year":"2023","journal-title":"Biol. Psychiatry"},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"914","DOI":"10.1111\/j.1582-4934.2008.00159.x","article-title":"S100B induces Tau protein hyperphosphorylation via Dickopff-1 up-regulation and disrupts the Wnt pathway in human neural stem cells","volume":"12","author":"Esposito","year":"2008","journal-title":"J. Cell. Mol. Med."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"1400","DOI":"10.1016\/j.neurobiolaging.2011.02.003","article-title":"AGEs induce Alzheimer-like tau pathology and memory deficit via RAGE-mediated GSK-3 activation","volume":"33","author":"Li","year":"2012","journal-title":"Neurobiol. Aging"},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"10039","DOI":"10.1021\/bi1016233","article-title":"Preparation and characterization of neurotoxic tau oligomers","volume":"49","author":"Jackson","year":"2010","journal-title":"Biochemistry"},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"14","DOI":"10.1186\/s40478-015-0199-x","article-title":"Amyloid accelerates tau propagation and toxicity in a model of early Alzheimer\u2019s disease","volume":"3","author":"Pooler","year":"2015","journal-title":"Acta Neuropathol. Commun."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1038\/nm.4443","article-title":"Amyloid-\u03b2 plaques enhance Alzheimer\u2019s brain tau-seeded pathologies by facilitating neuritic plaque tau aggregation","volume":"24","author":"He","year":"2018","journal-title":"Nat. Med."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"1002","DOI":"10.1093\/hmg\/ddy017","article-title":"RAGE mediates accumulation in a mouse model of Alzheimer\u2019s disease via modulation of \u03b2- and \u03b3-secretase activity","volume":"27","author":"Fang","year":"2018","journal-title":"Hum. Mol. Genet."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"1394","DOI":"10.1080\/13880209.2022.2103718","article-title":"Network pharmacology approach to investigate the multitarget mechanisms of Zhishi Rhubarb Soup on acute cerebral infarction","volume":"60","author":"Shao","year":"2022","journal-title":"Pharm. Biol."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"946","DOI":"10.1038\/nm.1999","article-title":"Pivotal role of cerebral interleukin-17-producing gamma delta T cells in the delayed phase of ischemic brain injury","volume":"15","author":"Shichita","year":"2009","journal-title":"Nat. Med."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"911","DOI":"10.1038\/nm.2749","article-title":"Peroxiredoxin family proteins are key initiators of post-ischemic inflammation in the brain","volume":"18","author":"Shichita","year":"2012","journal-title":"Nat. Med."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"547","DOI":"10.14336\/AD.2019.0715","article-title":"Neuroprotective Effects of Endogenous Secretory Receptor for Advanced Glycation End-products in Brain Ischemia","volume":"11","author":"Shimizu","year":"2020","journal-title":"Aging Dis."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"220","DOI":"10.1016\/j.neuint.2011.12.008","article-title":"RAGE mediates vascular injury and inflammation after global cerebral ischemia","volume":"60","author":"Kamide","year":"2012","journal-title":"Neurochem. Int."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"2355","DOI":"10.1007\/s12035-023-03228-8","article-title":"Advanced Glycation End-Products (AGEs) Promote Endothelial Cell Pyroptosis under Cerebral Ischemia and Hypoxia via HIF-1\u03b1-RAGE-NLRP3","volume":"60","author":"Han","year":"2023","journal-title":"Mol. Neurobiol."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"23233","DOI":"10.1074\/jbc.M110.117457","article-title":"Advanced glycation end product (AGE)-receptor for AGE (RAGE) signaling and up-regulation of Egr1 in hypoxic macrophages","volume":"285","author":"Xu","year":"2010","journal-title":"J. Biol. Chem."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"115588","DOI":"10.1016\/j.expneurol.2025.115588","article-title":"Azeliragon attenuates cerebral infarction aggravation in diabetic rats: Receptor for advanced glycation end-product as a novel therapeutic target","volume":"397","author":"Lee","year":"2026","journal-title":"Exp. Neurol."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"1355","DOI":"10.2353\/ajpath.2008.070975","article-title":"Regulated intramembrane proteolysis of the low-density lipoprotein receptor related protein mediates ischemic cell death","volume":"172","author":"Polavarapu","year":"2008","journal-title":"Am. J. Pathol."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"1029","DOI":"10.1038\/nm1635","article-title":"Clearance of amyloid-\u03b2 by circulating lipoprotein receptors","volume":"13","author":"Sagare","year":"2007","journal-title":"Nat. Med."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1172\/JCI81108","article-title":"Endothelial LRP1 transports amyloid-\u03b2 1-42 across the blood-brain barrier","volume":"126","author":"Storck","year":"2016","journal-title":"J. Clin. Investig."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"8729398","DOI":"10.1155\/2022\/8729398","article-title":"Activation of LRP1 Ameliorates Cerebral Ischemia\/Reperfusion Injury and Cognitive Decline by Suppressing Neuroinflammation and Oxidative Stress through TXNIP\/NLRP3 Signaling Pathway in Mice","volume":"2022","author":"Yang","year":"2022","journal-title":"Oxid. Med. Cell. Longev."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"192","DOI":"10.1016\/j.brainres.2016.05.023","article-title":"Neuronal low-density lipoprotein receptor-related protein 1 (LRP1) enhances the antiapoptotic effect of intravenous immunoglobulin (IVIg) in ischemic stroke","volume":"1644","author":"Lok","year":"2016","journal-title":"Brain Res."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"1134","DOI":"10.1038\/s41467-022-28777-9","article-title":"Astrocytic phagocytosis contributes to demyelination after focal cortical ischemia in mice","volume":"13","author":"Wan","year":"2022","journal-title":"Nat. Commun."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"2054","DOI":"10.1016\/j.cmet.2024.05.016","article-title":"Astrocytic LRP1 enables mitochondria transfer to neurons and mitigates brain ischemic stroke by suppressing ARF1 actylation","volume":"36","author":"Zhou","year":"2024","journal-title":"Cell Metab."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1007\/BF00294424","article-title":"Reassessment of a new model of complete cerebral ischemia in rats. Method of induction of clinical death, pathophysiology and cerebrovascular pathology","volume":"83","author":"Pluta","year":"1991","journal-title":"Acta Neuropathol."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"1047","DOI":"10.3233\/JAD-150299","article-title":"Dysregulation of Amyloid-\u03b2 Protein Precursor, \u03b2-Secretase, Presenilin 1 and 2 Genes in the Rat Selectively Vulnerable CA1 Subfield of Hippocampus Following Transient Global Brain Ischemia","volume":"47","author":"Kocki","year":"2015","journal-title":"J. Alzheimer\u2019s Dis."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/27\/13\/5831\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,7]],"date-time":"2026-07-07T04:16:55Z","timestamp":1783397815000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/27\/13\/5831"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,6,28]]},"references-count":93,"journal-issue":{"issue":"13","published-online":{"date-parts":[[2026,7]]}},"alternative-id":["ijms27135831"],"URL":"https:\/\/doi.org\/10.3390\/ijms27135831","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,6,28]]}}}