{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,8]],"date-time":"2026-09-08T00:50:21Z","timestamp":1788828621358,"version":"build-2803163510"},"reference-count":157,"publisher":"MDPI AG","issue":"15","license":[{"start":{"date-parts":[[2022,7,29]],"date-time":"2022-07-29T00:00:00Z","timestamp":1659052800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"publisher","award":["NRF-2019M3E5D1A02069061"],"award-info":[{"award-number":["NRF-2019M3E5D1A02069061"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"publisher","award":["2020R1F1A1066362"],"award-info":[{"award-number":["2020R1F1A1066362"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002560","name":"Soonchunhyang University","doi-asserted-by":"publisher","award":["NRF-2019M3E5D1A02069061"],"award-info":[{"award-number":["NRF-2019M3E5D1A02069061"]}],"id":[{"id":"10.13039\/501100002560","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002560","name":"Soonchunhyang University","doi-asserted-by":"publisher","award":["2020R1F1A1066362"],"award-info":[{"award-number":["2020R1F1A1066362"]}],"id":[{"id":"10.13039\/501100002560","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>The low-density-lipoprotein receptor (LDLr) removes low-density lipoprotein (LDL), an endovascular transporter that carries cholesterol from the bloodstream to peripheral tissues. The maintenance of cholesterol content in the brain, which is important to protect brain function, is affected by LDLr. LDLr co-localizes with the insulin receptor and complements the internalization of LDL. In LDLr deficiency, LDL blood levels and insulin resistance increase, leading to abnormal cholesterol control and cognitive deficits in atherosclerosis. Defects in brain cholesterol metabolism lead to neuroinflammation and blood\u2013brain-barrier (BBB) degradation. Moreover, interactions between endoplasmic reticulum stress (ER stress) and mitochondria are induced by ox-LDL accumulation, apolipoprotein E (ApoE) regulates the levels of amyloid beta (A\u03b2) in the brain, and hypoxia is induced by apoptosis induced by the LDLr defect. This review summarizes the association between neurodegenerative brain disease and typical cognitive deficits.<\/jats:p>","DOI":"10.3390\/ijms23158384","type":"journal-article","created":{"date-parts":[[2022,7,31]],"date-time":"2022-07-31T23:37:29Z","timestamp":1659310649000},"page":"8384","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":37,"title":["Relationship between Brain Metabolic Disorders and Cognitive Impairment: LDL Receptor Defect"],"prefix":"10.3390","volume":"23","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4819-7450","authenticated-orcid":false,"given":"Dong-Yong","family":"Hong","sequence":"first","affiliation":[{"name":"Department of Neurosurgery, College of Medicine, Soonchunhyang University, Cheonan Hospital, Cheonan 31151, Korea"},{"name":"Soonchunhyang Institute of Medi-Bio Science (SIMS), Soon Chun Hyang University, Cheonan 31151, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2629-5225","authenticated-orcid":false,"given":"Dong-Hun","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, College of Medicine, Soonchunhyang University, Cheonan Hospital, Cheonan 31151, Korea"},{"name":"Soonchunhyang Institute of Medi-Bio Science (SIMS), Soon Chun Hyang University, Cheonan 31151, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ji-Young","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, College of Medicine, Soonchunhyang University, Cheonan Hospital, Cheonan 31151, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eun-Chae","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, College of Medicine, Soonchunhyang University, Cheonan Hospital, Cheonan 31151, Korea"},{"name":"Soonchunhyang Institute of Medi-Bio Science (SIMS), Soon Chun Hyang University, Cheonan 31151, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6304-2126","authenticated-orcid":false,"given":"Sang-Won","family":"Park","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, College of Medicine, Soonchunhyang University, Cheonan Hospital, Cheonan 31151, Korea"},{"name":"Soonchunhyang Institute of Medi-Bio Science (SIMS), Soon Chun Hyang University, Cheonan 31151, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2351-9679","authenticated-orcid":false,"given":"Man-Ryul","family":"Lee","sequence":"additional","affiliation":[{"name":"Soonchunhyang Institute of Medi-Bio Science (SIMS), Soon Chun Hyang University, Cheonan 31151, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4570-6763","authenticated-orcid":false,"given":"Jae-Sang","family":"Oh","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, College of Medicine, Soonchunhyang University, Cheonan Hospital, Cheonan 31151, Korea"},{"name":"Soonchunhyang Institute of Medi-Bio Science (SIMS), Soon Chun Hyang University, Cheonan 31151, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,7,29]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"196","DOI":"10.1177\/1479164111430243","article-title":"The association between insulin and low-density lipoprotein receptors","volume":"9","author":"Ramakrishnan","year":"2012","journal-title":"Diabetes Vasc. Dis. Res."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"213","DOI":"10.1111\/j.1432-1033.1988.tb14084.x","article-title":"Hormonal regulation of low-density lipoprotein (LDL) receptor activity in human hepatoma Hep G2 cells: Insulin increases LDL receptor activity and diminishes its suppression by exogenous LDL","volume":"174","author":"Wade","year":"1988","journal-title":"Eur. J. Biochem."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"190","DOI":"10.1016\/j.mcn.2005.02.006","article-title":"Multiple mechanisms mediate cholesterol-induced synaptogenesis in a CNS neuron","volume":"29","author":"Goritz","year":"2005","journal-title":"Mol. Cell. Neurosci."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"251","DOI":"10.1038\/nrn2593","article-title":"Plasma membrane expansion: A neuron\u2019s Herculean task","volume":"10","author":"Pfenninger","year":"2009","journal-title":"Nat. Rev. Neurosci."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"831","DOI":"10.1016\/j.cell.2006.10.030","article-title":"Molecular anatomy of a trafficking organelle","volume":"127","author":"Takamori","year":"2006","journal-title":"Cell"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"357","DOI":"10.1016\/j.plipres.2011.06.002","article-title":"Cholesterol metabolism in neurons and astrocytes","volume":"50","author":"Pfrieger","year":"2011","journal-title":"Prog. Lipid Res."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"595","DOI":"10.1242\/jcs.060681","article-title":"Cholesterol reduction impairs exocytosis of synaptic vesicles","volume":"123","author":"Linetti","year":"2010","journal-title":"J. Cell Sci."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"17068","DOI":"10.1523\/JNEUROSCI.4067-10.2010","article-title":"Neuronal LRP1 knockout in adult mice leads to impaired brain lipid metabolism and progressive, age-dependent synapse loss and neurodegeneration","volume":"30","author":"Liu","year":"2010","journal-title":"J. Neurosci."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"66","DOI":"10.1016\/j.neuron.2007.08.008","article-title":"Amyloid precursor protein regulates brain apolipoprotein E and cholesterol metabolism through lipoprotein receptor LRP1","volume":"56","author":"Liu","year":"2007","journal-title":"Neuron"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1016\/j.jacl.2009.11.003","article-title":"Altered cholesterol and fatty acid metabolism in Huntington disease","volume":"4","author":"Block","year":"2010","journal-title":"J. Clin. Lipidol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"284","DOI":"10.1038\/nrn3012","article-title":"Linking lipids to Alzheimer\u2019s disease: Cholesterol and beyond","volume":"12","author":"Kim","year":"2011","journal-title":"Nat. Rev. Neurosci."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1016\/j.expneurol.2010.04.006","article-title":"Statins: Multiple neuroprotective mechanisms in neurodegenerative diseases","volume":"230","author":"Wang","year":"2011","journal-title":"Exp. Neurol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"475","DOI":"10.1111\/j.1471-4159.2008.05415.x","article-title":"High cholesterol-induced neuroinflammation and amyloid precursor protein processing correlate with loss of working memory in mice","volume":"106","author":"Thirumangalakudi","year":"2008","journal-title":"J. Neurochem."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"415","DOI":"10.1007\/s00702-013-1107-9","article-title":"Hypercholesterolemia induces short-term spatial memory impairments in mice: Up-regulation of acetylcholinesterase activity as an early and causal event?","volume":"121","author":"Moreira","year":"2014","journal-title":"J. Neural Transm."},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Rutkowsky, J.M., Lee, L.L., Puchowicz, M., Golub, M.S., Befroy, D.E., Wilson, D.W., Anderson, S., Cline, G., Bini, J., and Borkowski, K. (2018). Reduced cognitive function, increased blood-brain-barrier transport and inflammatory responses, and altered brain metabolites in LDLr\u2212\/\u2212and C57BL\/6 mice fed a western diet. PLoS ONE, 13.","DOI":"10.1371\/journal.pone.0191909"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"411","DOI":"10.1016\/j.mito.2010.05.014","article-title":"Mitochondrial dysfunction: A potential link between neuroinflammation and neurodegeneration?","volume":"10","author":"Witte","year":"2010","journal-title":"Mitochondrion"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"106","DOI":"10.1016\/j.neuroscience.2017.02.041","article-title":"EZH2 regulates spinal neuroinflammation in rats with neuropathic pain","volume":"349","author":"Yadav","year":"2017","journal-title":"Neuroscience"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1016\/j.neulet.2004.05.057","article-title":"Effects of high cholesterol diet on gliosis in apolipoprotein E knockout mice: Implications for Alzheimer\u2019s disease and stroke","volume":"369","author":"Crisby","year":"2004","journal-title":"Neurosci. Lett."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"146","DOI":"10.1016\/j.clnu.2005.10.004","article-title":"Protective effect of red wine on oxidative stress and antioxidant enzyme activities in the brain and kidney induced by feeding high cholesterol in rats","volume":"25","author":"Montilla","year":"2006","journal-title":"Clin. Nutr."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"5153","DOI":"10.1016\/S0021-9258(19)42341-7","article-title":"Binding and degradation of low density lipoproteins by cultured human fibroblasts. Comparison of cells from a normal subject and from a patient with homozygous familial hypercholesterolemia","volume":"249","author":"Goldstein","year":"1974","journal-title":"J. Biol. Chem."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"629","DOI":"10.1016\/0092-8674(77)90263-X","article-title":"Genetics of the LDL receptor: Evidence that the mutations affecting binding and internalization are allelic","volume":"12","author":"Goldstein","year":"1977","journal-title":"Cell"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"4288","DOI":"10.1073\/pnas.71.11.4288","article-title":"Esterification of low density lipoprotein cholesterol in human fibroblasts and its absence in homozygous familial hypercholesterolemia","volume":"71","author":"Goldstein","year":"1974","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"2804","DOI":"10.1073\/pnas.70.10.2804","article-title":"Familial hypercholesterolemia: Identification of a defect in the regulation of 3-hydroxy-3-methylglutaryl coenzyme A reductase activity associated with overproduction of cholesterol","volume":"70","author":"Goldstein","year":"1973","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"788","DOI":"10.1073\/pnas.71.3.788","article-title":"Familial hypercholesterolemia: Defective binding of lipoproteins to cultured fibroblasts associated with impaired regulation of 3-hydroxy-3-methylglutaryl coenzyme A reductase activity","volume":"71","author":"Brown","year":"1974","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1126\/science.185.4145.61","article-title":"Expression of the familial hypercholesterolemia gene in heterozygotes: Mechanism for a dominant disorder in man","volume":"185","author":"Brown","year":"1974","journal-title":"Science"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"11041","DOI":"10.1073\/pnas.96.20.11041","article-title":"A proteolytic pathway that controls the cholesterol content of membranes, cells, and blood","volume":"96","author":"Brown","year":"1999","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"12027","DOI":"10.1073\/pnas.1534923100","article-title":"Combined analysis of oligonucleotide microarray data from transgenic and knockout mice identifies direct SREBP target genes","volume":"100","author":"Horton","year":"2003","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"512","DOI":"10.1016\/j.cmet.2008.10.008","article-title":"Switch-like control of SREBP-2 transport triggered by small changes in ER cholesterol: A delicate balance","volume":"8","author":"Radhakrishnan","year":"2008","journal-title":"Cell Metab."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1016\/j.cca.2019.09.022","article-title":"Cholesterol in LDL receptor recycling and degradation","volume":"500","author":"Yang","year":"2020","journal-title":"Clin. Chim. Acta"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"26483","DOI":"10.1074\/jbc.M504041200","article-title":"Insig required for sterol-mediated inhibition of Scap\/SREBP binding to COPII proteins in vitro","volume":"280","author":"Sun","year":"2005","journal-title":"J. Biol. Chem."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"489","DOI":"10.1016\/S0092-8674(02)00872-3","article-title":"Crucial step in cholesterol homeostasis: Sterols promote binding of SCAP to INSIG-1, a membrane protein that facilitates retention of SREBPs in ER","volume":"110","author":"Yang","year":"2002","journal-title":"Cell"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"12753","DOI":"10.1073\/pnas.162488899","article-title":"Insig-2, a second endoplasmic reticulum protein that binds SCAP and blocks export of sterol regulatory element-binding proteins","volume":"99","author":"Yabe","year":"2002","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1394","DOI":"10.1126\/science.1060458","article-title":"Autosomal recessive hypercholesterolemia caused by mutations in a putative LDL receptor adaptor protein","volume":"292","author":"Garcia","year":"2001","journal-title":"Science"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"44044","DOI":"10.1074\/jbc.M208539200","article-title":"ARH is a modular adaptor protein that interacts with the LDL receptor, clathrin, and AP-2","volume":"277","author":"He","year":"2002","journal-title":"J. Biol. Chem."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"34023","DOI":"10.1074\/jbc.M405242200","article-title":"The modular adaptor protein ARH is required for low density lipoprotein (LDL) binding and internalization but not for LDL receptor clustering in coated pits","volume":"279","author":"Michaely","year":"2004","journal-title":"J. Biol. Chem."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"1550","DOI":"10.1194\/jlr.M033167","article-title":"S-nitrosylation of ARH is required for LDL uptake by the LDL receptor","volume":"54","author":"Zhao","year":"2013","journal-title":"J. Lipid Res."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"809","DOI":"10.1194\/jlr.M063065","article-title":"Endocytic adaptors Arh and Dab2 control homeostasis of circulatory cholesterol","volume":"57","author":"Tao","year":"2016","journal-title":"J. Lipid Res."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"50630","DOI":"10.1074\/jbc.M410077200","article-title":"Post-transcriptional regulation of low density lipoprotein receptor protein by proprotein convertase subtilisin\/kexin type 9a in mouse liver","volume":"279","author":"Park","year":"2004","journal-title":"J. Biol. Chem."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"254","DOI":"10.1007\/s13238-014-0131-3","article-title":"Cholesterol metabolism and homeostasis in the brain","volume":"6","author":"Zhang","year":"2015","journal-title":"Protein Cell"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"897","DOI":"10.1146\/annurev.bi.46.070177.004341","article-title":"The low-density lipoprotein pathway and its relation to atherosclerosis","volume":"46","author":"Goldstein","year":"1977","journal-title":"Annu. Rev. Biochem."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"34","DOI":"10.1126\/science.3513311","article-title":"A receptor-mediated pathway for cholesterol homeostasis","volume":"232","author":"Brown","year":"1986","journal-title":"Science"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"535","DOI":"10.1146\/annurev.biochem.74.082803.133354","article-title":"Structure and physiologic function of the low-density lipoprotein receptor","volume":"74","author":"Jeon","year":"2005","journal-title":"Annu. Rev. Biochem."},{"key":"ref_43","first-page":"19","article-title":"Low-density lipoprotein receptor (LDLR) family orchestrates cholesterol homeostasis","volume":"85","author":"Go","year":"2012","journal-title":"Yale J. Biol. Med."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"351","DOI":"10.1016\/0092-8674(77)90022-8","article-title":"Role of the coated endocytic vesicle in the uptake of receptor-bound low density lipoprotein in human fibroblasts","volume":"10","author":"Anderson","year":"1977","journal-title":"Cell"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"1351","DOI":"10.1002\/bies.20151","article-title":"Insulin and its receptor: Structure, function and evolution","volume":"26","year":"2004","journal-title":"Bioessays"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"376","DOI":"10.1016\/j.tibs.2008.06.003","article-title":"The insulin receptor: A prototype for dimeric, allosteric membrane receptors?","volume":"33","year":"2008","journal-title":"Trends Biochem. Sci."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"873","DOI":"10.1007\/s00018-007-6359-9","article-title":"Regulation of insulin receptor function","volume":"64","author":"Youngren","year":"2007","journal-title":"Cell Mol. Life Sci."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"S27","DOI":"10.1016\/0021-9150(94)05373-Q","article-title":"The dyslipoproteinemias of diabetes","volume":"110","author":"Steiner","year":"1994","journal-title":"Atherosclerosis"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"635","DOI":"10.1038\/s41574-019-0254-y","article-title":"The heterogeneous pathogenesis of type 1 diabetes mellitus","volume":"15","author":"Ilonen","year":"2019","journal-title":"Nat. Rev. Endocrinol."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"1068","DOI":"10.1016\/S0140-6736(13)62154-6","article-title":"Pathophysiology and treatment of type 2 diabetes: Perspectives on the past, present, and future","volume":"383","author":"Kahn","year":"2014","journal-title":"Lancet"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"46","DOI":"10.5897\/JPAP2013.0001","article-title":"The pathogenesis and pathophysiology of type 1 and type 2 diabetes mellitus","volume":"4","author":"Ozougwu","year":"2013","journal-title":"J. Physiol. Pathophysiol."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"2197","DOI":"10.1016\/S0021-9258(18)89537-0","article-title":"Proposed mechanism for increased insulin-mediated glucose transport in adipose cells from young, obese Zucker rats. Large intracellular pool of glucose transporters","volume":"260","author":"Lavau","year":"1985","journal-title":"J. Biol. Chem."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"767","DOI":"10.1210\/endo-114-3-767","article-title":"Permissive effect of insulin on the adenosine 3\u2032,5\u2032-monophosphate-dependent up-regulation of low density lipoprotein receptors and the stimulation of steroid release in bovine adrenal cortical cells","volume":"114","author":"Ill","year":"1984","journal-title":"Endocrinology"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"e22840","DOI":"10.1002\/jbt.22840","article-title":"A comprehensive account of insulin and LDL receptor activity over the years: A highlight on their signaling and functional role","volume":"35","author":"Chandra","year":"2021","journal-title":"J. Biochem. Mol. Toxicol."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"3020","DOI":"10.1038\/s41598-019-39559-7","article-title":"Low density lipoprotein mimics insulin action on autophagy and glucose uptake in endothelial cells","volume":"9","author":"Zhu","year":"2019","journal-title":"Sci. Rep."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"1482","DOI":"10.1016\/j.bbrc.2017.12.001","article-title":"MicroRNA-126 alleviates endothelial cells injury in atherosclerosis by restoring autophagic flux via inhibiting of PI3K\/Akt\/mTOR pathway","volume":"495","author":"Tang","year":"2018","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"566","DOI":"10.1038\/nn0602-861","article-title":"Decreasing hypothalamic insulin receptors causes hyperphagia and insulin resistance in rats","volume":"5","author":"Obici","year":"2002","journal-title":"Nat. Neurosci."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"3702","DOI":"10.7150\/ijbs.63512","article-title":"Suppression of neuronal cholesterol biosynthesis impairs brain functions through insulin-like growth factor I-Akt signaling","volume":"17","author":"Liu","year":"2021","journal-title":"Int. J. Biol. Sci."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"491","DOI":"10.1016\/0091-3057(93)90497-H","article-title":"Spatial learning deficit and reduced hippocampal ChAT activity in rats after an ICV injection of streptozotocin","volume":"44","author":"Blokland","year":"1993","journal-title":"Pharmacol. Biochem. Behav."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"89","DOI":"10.3233\/JAD-2006-9110","article-title":"Alzheimer Research Forum live discussion: Insulin resistance: A common axis linking Alzheimer\u2019s, depression, and metabolism?","volume":"9","author":"Kinoshita","year":"2006","journal-title":"J. Alzheimers Dis."},{"key":"ref_61","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. Alzheimers Dis."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"89","DOI":"10.3233\/JAD-2006-10113","article-title":"Therapeutic rescue of neurodegeneration in experimental type 3 diabetes: Relevance to Alzheimer\u2019s disease","volume":"10","author":"Tong","year":"2006","journal-title":"J. Alzheimers Dis."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"13","DOI":"10.3233\/JAD-2006-9102","article-title":"Intracerebral streptozotocin model of type 3 diabetes: Relevance to sporadic Alzheimer\u2019s disease","volume":"9","author":"Rivera","year":"2006","journal-title":"J. Alzheimers Dis."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"a004697","DOI":"10.1101\/cshperspect.a004697","article-title":"Membrane organization and lipid rafts","volume":"3","author":"Simons","year":"2011","journal-title":"Cold Spring Harb. Perspect. Biol."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"369","DOI":"10.1007\/s12013-017-0792-7","article-title":"High Cholesterol\/Low Cholesterol: Effects in Biological Membranes: A Review","volume":"7","author":"Subczynski","year":"2017","journal-title":"Cell Biochem. Biophys."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"105215","DOI":"10.1016\/j.phrs.2020.105215","article-title":"Cholesterol homeostasis: Researching a dialogue between the brain and peripheral tissues","volume":"163","author":"Gliozzi","year":"2021","journal-title":"Pharmacol. Res."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"781","DOI":"10.1038\/ncb1035","article-title":"The endoplasmic reticulum is the site of cholesterol-induced cytotoxicity in macrophages","volume":"5","author":"Feng","year":"2003","journal-title":"Nat. Cell Biol."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"905","DOI":"10.1172\/JCI0216452","article-title":"Consequences of cellular cholesterol accumulation: Basic concepts and physiological implications","volume":"110","author":"Tabas","year":"2002","journal-title":"J. Clin. Investig."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"170","DOI":"10.1016\/j.chemphyslip.2016.02.011","article-title":"Cholesterol homeostasis: How do cells sense sterol excess?","volume":"199","author":"Howe","year":"2016","journal-title":"Chem. Phys. Lipids"},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"287","DOI":"10.1515\/BC.2009.035","article-title":"Central nervous system: Cholesterol turnover, brain development and neurodegeneration","volume":"390","author":"Dietschy","year":"2009","journal-title":"Biol. Chem."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"1375","DOI":"10.1194\/jlr.R400004-JLR200","article-title":"Thematic review series: Brain Lipids. Cholesterol metabolism in the central nervous system during early development and in the mature animal","volume":"45","author":"Dietschy","year":"2004","journal-title":"J. Lipid Res."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"445","DOI":"10.1007\/s11745-014-3895-6","article-title":"PCSK9 is present in human cerebrospinal fluid and is maintained at remarkably constant concentrations throughout the course of the day","volume":"49","author":"Chen","year":"2014","journal-title":"Lipids"},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"315","DOI":"10.3233\/JAD-160411","article-title":"Increased PCSK9 Cerebrospinal Fluid Concentrations in Alzheimer\u2019s Disease","volume":"55","author":"Zimetti","year":"2017","journal-title":"J. Alzheimers Dis."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"120","DOI":"10.3389\/fnagi.2019.00120","article-title":"Proprotein Convertase Subtilisin\/Kexin Type 9, Brain Cholesterol Homeostasis and Potential Implication for Alzheimer\u2019s Disease","volume":"11","author":"Adorni","year":"2019","journal-title":"Front Aging Neurosci."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"97","DOI":"10.3233\/JAD-200541","article-title":"High Cholesterol Diet Exacerbates Blood-Brain Barrier Disruption in LDLr\u2212\/\u2212 Mice: Impact on Cognitive Function","volume":"78","author":"Engel","year":"2020","journal-title":"J. Alzheimers Dis."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"19339","DOI":"10.18632\/aging.203320","article-title":"Characterization of familial hypercholesterolemia in Taiwanese ischemic stroke patients","volume":"13","author":"Tung","year":"2021","journal-title":"Aging"},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"2578","DOI":"10.1016\/j.jacc.2016.03.520","article-title":"Diagnostic Yield and Clinical Utility of Sequencing Familial Hypercholesterolemia Genes in Patients With Severe Hypercholesterolemia","volume":"67","author":"Khera","year":"2016","journal-title":"J. Am. Coll Cardiol."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"50","DOI":"10.1016\/j.atherosclerosis.2020.05.004","article-title":"A systematic review of LDLR, PCSK9, and APOB variants in Asia","volume":"305","author":"Mahdieh","year":"2020","journal-title":"Atherosclerosis"},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"66","DOI":"10.3390\/genes12010066","article-title":"The LDLR, APOB, and PCSK9 Variants of Index Patients with Familial Hypercholesterolemia in Russia","volume":"12","author":"Meshkov","year":"2021","journal-title":"Genes"},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"323","DOI":"10.1016\/S1537-1891(02)00200-8","article-title":"Tight junctions of the blood-brain barrier: Development, composition and regulation","volume":"38","author":"Wolburg","year":"2002","journal-title":"Vascul Pharmacol."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"1375","DOI":"10.2174\/1570159X16666180222164809","article-title":"The Role of VE-cadherin in Blood-brain Barrier Integrity Under Central Nervous System Pathological Conditions","volume":"16","author":"Li","year":"2018","journal-title":"Curr. Neuropharmacol."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1038\/nrn1824","article-title":"Astrocyte-endothelial interactions at the blood-brain barrier","volume":"7","author":"Abbott","year":"2006","journal-title":"Nat. Rev. Neurosci."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"1339","DOI":"10.1093\/gerona\/glu080","article-title":"Aging exacerbates obesity-induced cerebromicrovascular rarefaction, neurovascular uncoupling, and cognitive decline in mice","volume":"69","author":"Tucsek","year":"2014","journal-title":"J. Gerontol. Biol. Sci. Med. Sci."},{"key":"ref_84","doi-asserted-by":"crossref","unstructured":"Deng, J., Zhao, F., Yu, X., Zhao, Y., Li, D., Shi, H., and Sun, Y. (2014). Expression of aquaporin 4 and breakdown of the blood-brain barrier after hypoglycemia-induced brain edema in rats. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0107022"},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"90","DOI":"10.3390\/cells8020090","article-title":"Aquaporin-4 Water Channel in the Brain and Its Implication for Health and Disease","volume":"8","author":"Mader","year":"2019","journal-title":"Cells"},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"102815","DOI":"10.1016\/j.jaut.2022.102815","article-title":"Lipoprotein oxidation may underlie the paradoxical association of low cholesterol with coronary atherosclerotic risk in rheumatoid arthritis","volume":"129","author":"Karpouzas","year":"2022","journal-title":"J. Autoimmun."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"1975","DOI":"10.1194\/jlr.M600064-JLR200","article-title":"OxLDL immune complexes activate complement and induce cytokine production by MonoMac 6 cells and human macrophages","volume":"47","author":"Saad","year":"2006","journal-title":"J. Lipid Res."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1016\/j.neubiorev.2021.06.017","article-title":"The lipid paradox in neuroprogressive disorders: Causes and consequences","volume":"128","author":"Morris","year":"2021","journal-title":"Neurosci. Biobehav. Rev."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"1083","DOI":"10.1016\/j.bbalip.2015.02.010","article-title":"Cholesterol in myelin biogenesis and hypomyelinating disorders","volume":"1851","author":"Saher","year":"2015","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"330","DOI":"10.1186\/s12974-020-01988-x","article-title":"Low-density lipoprotein receptor (LDLR) regulates NLRP3-mediated neuronal pyroptosis following cerebral ischemia\/reperfusion injury","volume":"17","author":"Sun","year":"2020","journal-title":"J. Neuroinflamm."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"953","DOI":"10.3390\/biomedicines10050953","article-title":"Neuroinflammation in Post-Traumatic Stress Disorder","volume":"10","author":"Lee","year":"2022","journal-title":"Biomedicines"},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"1567","DOI":"10.1007\/s10753-012-9472-3","article-title":"Oxidized LDLs inhibit TLR-induced IL-10 production by monocytes: A new aspect of pathogen-accelerated atherosclerosis","volume":"35","author":"Bzowska","year":"2012","journal-title":"Inflammation"},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"235","DOI":"10.1016\/j.cell.2008.02.043","article-title":"Identification of oxidative stress and Toll-like receptor 4 signaling as a key pathway of acute lung injury","volume":"133","author":"Imai","year":"2008","journal-title":"Cell"},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"148","DOI":"10.1038\/cmi.2015.95","article-title":"Molecular mechanisms regulating NLRP3 inflammasome activation","volume":"13","author":"Jo","year":"2016","journal-title":"Cell Mol. Immunol."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"205","DOI":"10.1111\/bpa.12476","article-title":"A brain in flame; do inflammasomes and pyroptosis influence stroke pathology?","volume":"27","author":"Barrington","year":"2017","journal-title":"Brain Pathol."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"3955","DOI":"10.1242\/jcs.207365","article-title":"Inflammasome activation and assembly at a glance","volume":"130","author":"Malik","year":"2017","journal-title":"J. Cell Sci."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"645","DOI":"10.1002\/jnr.24385","article-title":"Gasdermin D serves as a key executioner of pyroptosis in experimental cerebral ischemia and reperfusion model both in vivo and in vitro","volume":"97","author":"Zhang","year":"2019","journal-title":"J. Neurosci. Res."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"62","DOI":"10.1016\/j.cca.2020.06.044","article-title":"Pyroptosis: A pro-inflammatory type of cell death in cardiovascular disease","volume":"510","author":"Wang","year":"2020","journal-title":"Clin. Chim. Acta"},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"715211","DOI":"10.3389\/fcell.2021.715211","article-title":"Gasdermin D Mediates Inflammation-Induced Defects in Reverse Cholesterol Transport and Promotes Atherosclerosis","volume":"9","author":"Opoku","year":"2021","journal-title":"Front Cell Dev. Biol."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"e76","DOI":"10.1161\/CIRCRESAHA.116.308362","article-title":"Ogg1-Dependent DNA Repair Regulates NLRP3 Inflammasome and Prevents Atherosclerosis","volume":"119","author":"Tumurkhuu","year":"2016","journal-title":"Circ. Res."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"2321","DOI":"10.1128\/IAI.73.4.2321-2326.2005","article-title":"Lipopolysaccharide is transferred from high-density to low-density lipoproteins by lipopolysaccharide-binding protein and phospholipid transfer protein","volume":"73","author":"Levels","year":"2005","journal-title":"Infect Immun."},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"258ra143","DOI":"10.1126\/scitranslmed.3008782","article-title":"PCSK9 is a critical regulator of the innate immune response and septic shock outcome","volume":"6","author":"Walley","year":"2014","journal-title":"Sci. Transl. Med."},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"2345","DOI":"10.1002\/jcp.27254","article-title":"PCSK9: A novel inflammation modulator in atherosclerosis?","volume":"234","author":"Tang","year":"2019","journal-title":"J. Cell Physiol."},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"453","DOI":"10.1016\/j.ceb.2006.06.004","article-title":"Critical dependence of neurons on mitochondrial dynamics","volume":"18","author":"Chen","year":"2006","journal-title":"Curr. Opin. Cell Biol."},{"key":"ref_105","first-page":"612","article-title":"Multisociety Consensus Quality Improvement Revised Consensus Statement for Endovascular Therapy of Acute Ischemic Stroke","volume":"13","author":"Sacks","year":"2018","journal-title":"Int. J. Stroke."},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"1583","DOI":"10.3390\/molecules24081583","article-title":"Oxidative Stress: A Key Modulator in Neurodegenerative Diseases","volume":"24","author":"Singh","year":"2019","journal-title":"Molecules"},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"1994","DOI":"10.1002\/2211-5463.12740","article-title":"Endoplasmic reticulum quality control of LDLR variants associated with familial hypercholesterolemia","volume":"9","author":"Kizhakkedath","year":"2019","journal-title":"FEBS Open Bio."},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"468","DOI":"10.1074\/jbc.M507071200","article-title":"Retention of mutant low density lipoprotein receptor in endoplasmic reticulum (ER) leads to ER stress","volume":"281","author":"Ranheim","year":"2006","journal-title":"J. Biol. Chem."},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"570355","DOI":"10.3389\/fgene.2020.570355","article-title":"Proteostasis Regulation in the Endoplasmic Reticulum: An Emerging Theme in the Molecular Pathology and Therapeutic Management of Familial Hypercholesterolemia","volume":"11","author":"Oommen","year":"2020","journal-title":"Front Genet."},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"205","DOI":"10.1080\/1028415X.1998.11747230","article-title":"Dietary Antioxidant Deficiency Facilitates Cortical Spreading Depression Induced by Photoactivated Riboflavin","volume":"1","author":"Guedes","year":"1998","journal-title":"Nutr. Neurosci."},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"729","DOI":"10.2165\/00023210-200317100-00004","article-title":"Neuroprotective strategies in Parkinson\u2019s disease: An update on progress","volume":"17","author":"Mandel","year":"2003","journal-title":"CNS Drugs"},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"1884","DOI":"10.1002\/jnr.22011","article-title":"Decreased antioxidant enzyme activity and increased mitochondrial DNA damage in cellular models of Machado-Joseph disease","volume":"87","author":"Yu","year":"2009","journal-title":"J. Neurosci. Res."},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"4437","DOI":"10.1021\/acs.biochem.6b00469","article-title":"Lectin-like Oxidized Low-Density Lipoprotein (LDL) Receptor (LOX-1): A Chameleon Receptor for Oxidized LDL","volume":"55","author":"Zeya","year":"2016","journal-title":"Biochemistry"},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"1693","DOI":"10.2174\/0929867325666180508100950","article-title":"Role of Ox-LDL and LOX-1 in Atherogenesis","volume":"26","author":"Kattoor","year":"2019","journal-title":"Curr. Med. Chem."},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"191","DOI":"10.1016\/j.yexcr.2019.04.002","article-title":"PACS2 is required for ox-LDL-induced endothelial cell apoptosis by regulating mitochondria-associated ER membrane formation and mitochondrial Ca(2+) elevation","volume":"379","author":"Yu","year":"2019","journal-title":"Exp. Cell Res."},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"118","DOI":"10.1016\/j.freeradbiomed.2017.02.006","article-title":"Dual signaling evoked by oxidized LDLs in vascular cells","volume":"106","author":"Bacchetti","year":"2017","journal-title":"Free Radic. Biol. Med."},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"841","DOI":"10.3109\/10715762.2014.929122","article-title":"LOX-1 and ROS, inseparable factors in the process of endothelial damage","volume":"48","author":"Lubrano","year":"2014","journal-title":"Free Radic Res."},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"714653","DOI":"10.1155\/2013\/714653","article-title":"The role of oxidized low-density lipoproteins in atherosclerosis: The myths and the facts","volume":"2013","author":"Maiolino","year":"2013","journal-title":"Mediat. Inflamm."},{"key":"ref_119","doi-asserted-by":"crossref","unstructured":"Zhou, Y.D., Cao, X.Q., Liu, Z.H., Cao, Y.J., Liu, C.F., Zhang, Y.L., and Xie, Y. (2016). Rapamycin Inhibits Oxidized Low Density Lipoprotein Uptake in Human Umbilical Vein Endothelial Cells via mTOR\/NF-\u03baB\/LOX-1 Pathway. PLoS ONE, 11.","DOI":"10.1371\/journal.pone.0146777"},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"2859","DOI":"10.1007\/s00018-012-1194-z","article-title":"LOX-1 in atherosclerosis: Biological functions and pharmacological modifiers","volume":"70","author":"Xu","year":"2013","journal-title":"Cell Mol. Life Sci."},{"key":"ref_121","doi-asserted-by":"crossref","first-page":"42","DOI":"10.1007\/s11883-017-0678-6","article-title":"Oxidative Stress in Atherosclerosis","volume":"19","author":"Kattoor","year":"2017","journal-title":"Curr. Atheroscler Rep."},{"key":"ref_122","doi-asserted-by":"crossref","first-page":"453","DOI":"10.1161\/CIRCRESAHA.109.203711","article-title":"Chronic endoplasmic reticulum stress activates unfolded protein response in arterial endothelium in regions of susceptibility to atherosclerosis","volume":"105","author":"Civelek","year":"2009","journal-title":"Circ. Res."},{"key":"ref_123","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1038\/nrm3270","article-title":"The unfolded protein response: Controlling cell fate decisions under ER stress and beyond","volume":"13","author":"Hetz","year":"2012","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_124","doi-asserted-by":"crossref","first-page":"20","DOI":"10.1016\/j.tcb.2003.11.001","article-title":"A trip to the ER: Coping with stress","volume":"14","author":"Rutkowski","year":"2004","journal-title":"Trends Cell Biol."},{"key":"ref_125","doi-asserted-by":"crossref","first-page":"839","DOI":"10.1161\/CIRCRESAHA.110.224766","article-title":"The role of endoplasmic reticulum stress in the progression of atherosclerosis","volume":"107","author":"Tabas","year":"2010","journal-title":"Circ. Res."},{"key":"ref_126","doi-asserted-by":"crossref","first-page":"9270107","DOI":"10.1155\/2020\/9270107","article-title":"Role of Endoplasmic Reticulum Stress in Atherosclerosis and Its Potential as a Therapeutic Target","volume":"2020","author":"Yang","year":"2020","journal-title":"Oxid Med. Cell Longev."},{"key":"ref_127","doi-asserted-by":"crossref","first-page":"237","DOI":"10.1093\/cvr\/cvv097","article-title":"Distinct mPTP activation mechanisms in ischaemia-reperfusion: Contributions of Ca2+, ROS, pH, and inorganic polyphosphate","volume":"106","author":"Seidlmayer","year":"2015","journal-title":"Cardiovasc. Res."},{"key":"ref_128","doi-asserted-by":"crossref","first-page":"260","DOI":"10.1016\/j.redox.2015.08.010","article-title":"Calcium and ROS: A mutual interplay","volume":"6","author":"Bertram","year":"2015","journal-title":"Redox Biol."},{"key":"ref_129","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1111\/j.1469-7793.2000.00057.x","article-title":"Mitochondria and calcium: From cell signalling to cell death","volume":"529","author":"Duchen","year":"2000","journal-title":"J. Physiol."},{"key":"ref_130","doi-asserted-by":"crossref","first-page":"716","DOI":"10.1002\/biof.1673","article-title":"Mitochondrial dysfunction and endoplasmic reticulum stress in the promotion of fibrosis in obstructive nephropathy induced by unilateral ureteral obstruction","volume":"46","author":"Bellido","year":"2020","journal-title":"Biofactors"},{"key":"ref_131","doi-asserted-by":"crossref","first-page":"4999","DOI":"10.1111\/febs.12353","article-title":"In the eye of the storm: Mitochondrial damage during heart and brain ischaemia","volume":"280","author":"Borutaite","year":"2013","journal-title":"FEBS J."},{"key":"ref_132","doi-asserted-by":"crossref","first-page":"98","DOI":"10.1038\/47513","article-title":"Caspase-12 mediates endoplasmic-reticulum-specific apoptosis and cytotoxicity by amyloid-beta","volume":"403","author":"Nakagawa","year":"2000","journal-title":"Nature"},{"key":"ref_133","doi-asserted-by":"crossref","first-page":"1423","DOI":"10.1038\/sj.cdd.4401950","article-title":"Mechanisms of cytochrome c release from mitochondria","volume":"13","author":"Garrido","year":"2006","journal-title":"Cell Death Differ."},{"key":"ref_134","doi-asserted-by":"crossref","first-page":"3209","DOI":"10.1242\/jcs.073643","article-title":"Regulation of the Apaf-1-caspase-9 apoptosome","volume":"123 Pt 19","author":"Bratton","year":"2010","journal-title":"J. Cell Sci."},{"key":"ref_135","doi-asserted-by":"crossref","first-page":"11","DOI":"10.5483\/BMBRep.2008.41.1.011","article-title":"The role of mitochondria in apoptosis","volume":"41","author":"Jeong","year":"2008","journal-title":"BMB Rep."},{"key":"ref_136","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1016\/j.neuroscience.2011.09.009","article-title":"Positive correlation between elevated plasma cholesterol levels and cognitive impairments in LDL receptor knockout mice: Relevance of cortico-cerebral mitochondrial dysfunction and oxidative stress","volume":"197","author":"Hort","year":"2011","journal-title":"Neuroscience"},{"key":"ref_137","doi-asserted-by":"crossref","first-page":"1331","DOI":"10.1166\/jnn.2021.18633","article-title":"Effects of Atorvastatin Combined with Nano-Selenium on Blood Lipids and Oxidative Stress in Atherosclerotic Rats","volume":"21","author":"Han","year":"2021","journal-title":"J. Nanosci. Nanotechnol."},{"key":"ref_138","doi-asserted-by":"crossref","first-page":"495","DOI":"10.3233\/JAD-2012-120541","article-title":"Age-related cognitive decline in hypercholesterolemic LDL receptor knockout mice (LDLr\u2212\/\u2212): Evidence of antioxidant imbalance and increased acetylcholinesterase activity in the prefrontal cortex","volume":"32","author":"Moreira","year":"2012","journal-title":"J. Alzheimers Dis."},{"key":"ref_139","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1016\/j.atherosclerosissup.2017.07.004","article-title":"Detection of familial hypercholesterolemia in patients from a general practice database","volume":"29","author":"Casula","year":"2017","journal-title":"Atheroscler Suppl."},{"key":"ref_140","doi-asserted-by":"crossref","first-page":"15","DOI":"10.2217\/pme-2018-0067","article-title":"APOE genotypes in Lebanon: Distribution and association with hypercholesterolemia and Alzheimer\u2019s disease","volume":"16","author":"Costanian","year":"2019","journal-title":"Per Med."},{"key":"ref_141","doi-asserted-by":"crossref","first-page":"2413","DOI":"10.1016\/j.neuron.2021.05.034","article-title":"Overexpressing low-density lipoprotein receptor reduces tau-associated neurodegeneration in relation to apoE-linked mechanisms","volume":"109","author":"Shi","year":"2021","journal-title":"Neuron"},{"key":"ref_142","doi-asserted-by":"crossref","first-page":"622","DOI":"10.1126\/science.3283935","article-title":"Apolipoprotein E: Cholesterol transport protein with expanding role in cell biology","volume":"240","author":"Mahley","year":"1988","journal-title":"Science"},{"key":"ref_143","doi-asserted-by":"crossref","first-page":"1469","DOI":"10.1007\/s11095-021-03098-6","article-title":"Interactions of Lipids, Lipoproteins, and Apolipoproteins with the Blood-Brain Barrier","volume":"38","author":"Rhea","year":"2021","journal-title":"Pharm. Res."},{"key":"ref_144","doi-asserted-by":"crossref","first-page":"163","DOI":"10.1016\/0006-8993(91)91092-F","article-title":"Apolipoprotein E immunoreactivity in cerebral amyloid deposits and neurofibrillary tangles in Alzheimer\u2019s disease and kuru plaque amyloid in Creutzfeldt-Jakob disease","volume":"541","author":"Namba","year":"1991","journal-title":"Brain Res."},{"key":"ref_145","doi-asserted-by":"crossref","first-page":"235","DOI":"10.1016\/0304-3940(92)90444-C","article-title":"Apolipoprotein E: A pathological chaperone protein in patients with cerebral and systemic amyloid","volume":"135","author":"Wisniewski","year":"1992","journal-title":"Neurosci. Lett."},{"key":"ref_146","doi-asserted-by":"crossref","first-page":"136","DOI":"10.1001\/jama.1997.03550020068040","article-title":"Apolipoprotein E epsilon4 associated with chronic traumatic brain injury in boxing","volume":"278","author":"Jordan","year":"1997","journal-title":"JAMA"},{"key":"ref_147","doi-asserted-by":"crossref","first-page":"555","DOI":"10.1212\/WNL.45.3.555","article-title":"Synergistic effects of traumatic head injury and apolipoprotein-epsilon 4 in patients with Alzheimer\u2019s disease","volume":"45","author":"Mayeux","year":"1995","journal-title":"Neurology"},{"key":"ref_148","doi-asserted-by":"crossref","first-page":"351","DOI":"10.1038\/jcbfm.2010.99","article-title":"Age-dependent effect of apolipoprotein E4 on functional outcome after controlled cortical impact in mice","volume":"31","author":"Mannix","year":"2011","journal-title":"J. Cereb. Blood Flow Metab."},{"key":"ref_149","doi-asserted-by":"crossref","first-page":"203","DOI":"10.1016\/j.neuron.2011.01.002","article-title":"Anti-a\u03b2 therapeutics in Alzheimer\u2019s disease: The need for a paradigm shift","volume":"69","author":"Golde","year":"2011","journal-title":"Neuron"},{"key":"ref_150","doi-asserted-by":"crossref","first-page":"349","DOI":"10.1038\/nn.3028","article-title":"The toxic A\u03b2 oligomer and Alzheimer\u2019s disease: An emperor in need of clothes","volume":"15","author":"Benilova","year":"2012","journal-title":"Nat. Neurosci."},{"key":"ref_151","doi-asserted-by":"crossref","first-page":"353","DOI":"10.1126\/science.1072994","article-title":"The amyloid hypothesis of Alzheimer\u2019s disease: Progress and problems on the road to therapeutics","volume":"297","author":"Hardy","year":"2002","journal-title":"Science"},{"key":"ref_152","doi-asserted-by":"crossref","first-page":"13959","DOI":"10.1074\/jbc.M111.288746","article-title":"Low-density lipoprotein receptor represents an apolipoprotein E-independent pathway of A\u03b2 uptake and degradation by astrocytes","volume":"287","author":"Basak","year":"2012","journal-title":"J. Biol. Chem."},{"key":"ref_153","doi-asserted-by":"crossref","first-page":"15502","DOI":"10.1073\/pnas.1206446109","article-title":"Low-density lipoprotein receptor overexpression enhances the rate of brain-to-blood A\u03b2 clearance in a mouse model of \u03b2-amyloidosis","volume":"109","author":"Castellano","year":"2012","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_154","doi-asserted-by":"crossref","first-page":"43","DOI":"10.3233\/JAD-132228","article-title":"Increased susceptibility to amyloid-\u03b2-induced neurotoxicity in mice lacking the low-density lipoprotein receptor","volume":"41","author":"Moreira","year":"2014","journal-title":"J. Alzheimers Dis."},{"key":"ref_155","doi-asserted-by":"crossref","first-page":"26","DOI":"10.1016\/j.atherosclerosis.2018.02.015","article-title":"Hyperlipidemia induces typical atherosclerosis development in Ldlr and Apoe deficient rats","volume":"271","author":"Zhao","year":"2018","journal-title":"Atherosclerosis"},{"key":"ref_156","doi-asserted-by":"crossref","first-page":"759","DOI":"10.1038\/s41577-018-0051-1","article-title":"Interplay between innate immunity and Alzheimer disease: APOE and TREM2 in the spotlight","volume":"18","author":"Shi","year":"2018","journal-title":"Nat. Rev. Immunol."},{"key":"ref_157","doi-asserted-by":"crossref","first-page":"212","DOI":"10.1016\/j.nbd.2004.01.015","article-title":"Low-density lipoprotein receptor-knockout mice display impaired spatial memory associated with a decreased synaptic density in the hippocampus","volume":"16","author":"Mulder","year":"2004","journal-title":"Neurobiol. 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