{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,1]],"date-time":"2026-05-01T04:13:56Z","timestamp":1777608836055,"version":"3.51.4"},"reference-count":85,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2023,4,28]],"date-time":"2023-04-28T00:00:00Z","timestamp":1682640000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100011011","name":"Junta de Andaluc\u00eda","doi-asserted-by":"publisher","award":["P18-RT-3324"],"award-info":[{"award-number":["P18-RT-3324"]}],"id":[{"id":"10.13039\/501100011011","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100011011","name":"Junta de Andaluc\u00eda","doi-asserted-by":"publisher","award":["P20-01061"],"award-info":[{"award-number":["P20-01061"]}],"id":[{"id":"10.13039\/501100011011","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100011011","name":"Junta de Andaluc\u00eda","doi-asserted-by":"publisher","award":["PID2019-110960GB-I00"],"award-info":[{"award-number":["PID2019-110960GB-I00"]}],"id":[{"id":"10.13039\/501100011011","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Ministry of Science and Innovation","award":["P18-RT-3324"],"award-info":[{"award-number":["P18-RT-3324"]}]},{"name":"Ministry of Science and Innovation","award":["P20-01061"],"award-info":[{"award-number":["P20-01061"]}]},{"name":"Ministry of Science and Innovation","award":["PID2019-110960GB-I00"],"award-info":[{"award-number":["PID2019-110960GB-I00"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Aging continues to be the main cause of the development of Alzheimer\u2019s, although it has been described that certain chronic inflammatory pathologies can negatively influence the progress of dementia, including obesity and hyperlipidemia. In this sense, previous studies have shown a relationship between low-density lipoprotein receptor (LDLR) and the amyloid-beta (A\u03b2) binding activity, one of the main neuropathological features of Alzheimer\u2019s disease (AD). LDLR is involved in several processes, including lipid transport, regulation of inflammatory response and lipid metabolism. From this perspective, LDLR\u2212\/\u2212 mice are a widely accepted animal model for the study of pathologies associated with alterations in lipid metabolism, such as familial hypercholesterolemia, cardiovascular diseases, metabolic syndrome, or early cognitive decline. In this context, we induced hyperlipidemia in LDLR\u2212\/\u2212 mice after feeding with a high-saturated fatty acid diet (HFD) for 44 weeks. LDLR\u2212\/\u2212-HFD mice exhibited obesity, hypertriglyceridemia, higher glucose levels, and early hepatic steatosis. In addition, HFD increased plasmatic APOE and ubiquitin 60S levels. These proteins are related to neuronal integrity and health maintenance. In agreement, we detected mild cognitive dysfunctions in mice fed with HFD, whereas LDLR\u2212\/\u2212-HFD mice showed a more severe and evident affectation. Our data suggest central nervous system dysfunction is associated with a well-established metabolic syndrome. As a late consequence, metabolic syndrome boots many behavioral and pathological alterations recognized in dementia, supporting that the control of metabolic parameters could improve cognitive preservation and prognosis.<\/jats:p>","DOI":"10.3390\/ijms24098042","type":"journal-article","created":{"date-parts":[[2023,4,28]],"date-time":"2023-04-28T10:51:52Z","timestamp":1682679112000},"page":"8042","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Metabolic Disturbance of High-Saturated Fatty Acid Diet in Cognitive Preservation"],"prefix":"10.3390","volume":"24","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2070-8834","authenticated-orcid":false,"given":"Antonio","family":"Rivas-Dom\u00ednguez","sequence":"first","affiliation":[{"name":"Department of Cellular Biology, University of Seville, 41009 Seville, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Himan","family":"Mohamed-Mohamed","sequence":"additional","affiliation":[{"name":"Department of Physiology, Faculty of Health Sciences (Ceuta), University of Granada, 51001 Ceuta, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3051-194X","authenticated-orcid":false,"given":"Margarita","family":"Jimenez-Palomares","sequence":"additional","affiliation":[{"name":"Department of Biomedicine, Biotechnology and Public Health, University of C\u00e1diz, 11003 C\u00e1diz, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8964-9935","authenticated-orcid":false,"given":"Victoria","family":"Garc\u00eda-Morales","sequence":"additional","affiliation":[{"name":"Department of Biomedicine, Biotechnology and Public Health, University of C\u00e1diz, 11003 C\u00e1diz, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Laura","family":"Martinez-Lopez","sequence":"additional","affiliation":[{"name":"Department of Cellular Biology, University of Seville, 41009 Seville, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Manuel Luis","family":"Orta","sequence":"additional","affiliation":[{"name":"Department of Cellular Biology, University of Seville, 41009 Seville, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9081-5366","authenticated-orcid":false,"given":"Juan Jos\u00e9","family":"Ramos-Rodriguez","sequence":"additional","affiliation":[{"name":"Department of Physiology, Faculty of Health Sciences (Ceuta), University of Granada, 51001 Ceuta, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Beatriz","family":"Bermudez-Pulgarin","sequence":"additional","affiliation":[{"name":"Department of Cellular Biology, University of Seville, 41009 Seville, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2023,4,28]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Fontbonne, A., Currie, A., Tounian, P., Picot, M.C., Foulatier, O., Nedelcu, M., and Nocca, D. (2023). Prevalence of Overweight and Obesity in France: The 2020 Obepi-Roche Study by the \u201cLigue Contre l\u2019Obesite\u201d. J. Clin. Med., 12.","DOI":"10.3390\/jcm12030925"},{"key":"ref_2","first-page":"157","article-title":"Prevalence of overweight and obesity in Aragon and variations according to health determinants","volume":"98","year":"2023","journal-title":"An. Pediatr."},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Schramm, S., Sorensen, T.I.A., Davidsen, M., and Tolstrup, J.S. (2023). Changes in adult obesity prevalence in Denmark, 1987\u20132021: Age-period-cohort analysis of nationally representative data. Eur. J. Public Health, ckad024.","DOI":"10.1093\/eurpub\/ckad024"},{"key":"ref_4","first-page":"s176","article-title":"Obesity: Definition, comorbidities, causes, and burden","volume":"22","author":"Apovian","year":"2016","journal-title":"Am. J. Manag. Care"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"715","DOI":"10.1111\/obr.12551","article-title":"Obesity: A chronic relapsing progressive disease process. A position statement of the World Obesity Federation","volume":"18","author":"Bray","year":"2017","journal-title":"Obes. Rev. Off. J. Int. Assoc. Study Obes."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"822","DOI":"10.1016\/j.drudis.2021.11.001","article-title":"Obesity and insulin resistance: Pathophysiology and treatment","volume":"27","author":"Tong","year":"2022","journal-title":"Drug Discov. Today"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1033","DOI":"10.1002\/gps.4094","article-title":"Risk factors for age at onset of dementia due to Alzheimer\u2019s disease in a sample of patients with low mean schooling from Sao Paulo, Brazil","volume":"29","author":"Bertolucci","year":"2014","journal-title":"Int. J. Geriatr. Psychiatry"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"127","DOI":"10.1016\/j.jns.2015.10.051","article-title":"Risk factors for cognitive and functional change in one year in patients with Alzheimer\u2019s disease dementia from Sao Paulo, Brazil","volume":"359","author":"Pivi","year":"2015","journal-title":"J. Neurol. Sci."},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Pardo-Moreno, T., Mohamed-Mohamed, H., Rivas-Dominguez, A., Garcia-Morales, V., Garcia-Lara, R.A., Suleiman-Martos, S., Bermudez-Pulgarin, B., and Ramos-Rodriguez, J.J. (2023). Poor Cognitive Agility Conservation in Obese Aging People. Biomedicines, 11.","DOI":"10.3390\/biomedicines11010138"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"237","DOI":"10.1016\/j.tins.2017.02.005","article-title":"Obesity-Induced Neuroinflammation: Beyond the Hypothalamus","volume":"40","author":"Muccioli","year":"2017","journal-title":"Trends Neurosci."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"465","DOI":"10.1016\/S1474-4422(17)30084-4","article-title":"Neurological consequences of obesity","volume":"16","author":"Hinder","year":"2017","journal-title":"Lancet. Neurol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1331","DOI":"10.3233\/JAD-200655","article-title":"Patterns of Regional Cerebral Blood Flow as a Function of Obesity in Adults","volume":"77","author":"Amen","year":"2020","journal-title":"J. Alzheimer\u2019s Dis. JAD"},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Woo, A., Botta, A., Shi, S.S.W., Paus, T., and Pausova, Z. (2022). Obesity-Related Neuroinflammation: Magnetic Resonance and Microscopy Imaging of the Brain. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms23158790"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"248","DOI":"10.1177\/1099800420951633","article-title":"Effect of Obesity on Cognitive Impairment in Vascular Dementia Rat Model via BDNF-ERK-CREB Pathway","volume":"23","author":"Kim","year":"2021","journal-title":"Biol. Res. Nurs."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"560","DOI":"10.1111\/j.1467-789X.2009.00699.x","article-title":"Cholesterol imbalance in adipocytes: A possible mechanism of adipocytes dysfunction in obesity","volume":"11","author":"Yu","year":"2010","journal-title":"Obes. Rev. Off. J. Int. Assoc. Study Obes."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"620","DOI":"10.1111\/joim.12838","article-title":"Connecting the brain cholesterol and renin-angiotensin systems: Potential role of statins and RAS-modifying medications in dementia","volume":"284","author":"Petek","year":"2018","journal-title":"J. Intern. Med."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"350","DOI":"10.1016\/j.brainres.2015.06.049","article-title":"Dietary cholesterol concentration affects synaptic plasticity and dendrite spine morphology of rabbit hippocampal neurons","volume":"1622","author":"Wang","year":"2015","journal-title":"Brain Res."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"329","DOI":"10.1056\/NEJMra0909142","article-title":"Alzheimer\u2019s disease","volume":"362","author":"Querfurth","year":"2010","journal-title":"N. Engl. J. Med."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"95","DOI":"10.1590\/1516-4446-2016-1991","article-title":"Associations of cerebrovascular metabolism genotypes with neuropsychiatric symptoms and age at onset of Alzheimer\u2019s disease dementia","volume":"39","author":"Oliveira","year":"2017","journal-title":"Rev. Bras. Psiquiatr."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"17093","DOI":"10.1038\/nrdp.2017.93","article-title":"Familial hypercholesterolaemia","volume":"3","author":"Defesche","year":"2017","journal-title":"Nat. Rev. Dis. Prim."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"98","DOI":"10.1016\/j.autneu.2010.07.010","article-title":"Hypercholesterolemia magnitude increases sympathetic modulation and coagulation in LDLr knockout mice","volume":"159","author":"Evangelho","year":"2011","journal-title":"Auton. Neurosci. Basic Clin."},{"key":"ref_22","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_23","doi-asserted-by":"crossref","first-page":"251","DOI":"10.1016\/j.neures.2007.07.004","article-title":"LDL receptor deficiency results in decreased cell proliferation and presynaptic bouton density in the murine hippocampus","volume":"59","author":"Mulder","year":"2007","journal-title":"Neurosci. Res."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"2330","DOI":"10.1002\/jcp.25767","article-title":"PCSK9 at the crossroad of cholesterol metabolism and immune function during infections","volume":"232","author":"Paciullo","year":"2017","journal-title":"J. Cell. Physiol."},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Katsouri, L., and Georgopoulos, S. (2011). Lack of LDL receptor enhances amyloid deposition and decreases glial response in an Alzheimer\u2019s disease mouse model. PLoS ONE, 6.","DOI":"10.1371\/journal.pone.0021880"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"bjac020","DOI":"10.1093\/chemse\/bjac020","article-title":"Short-term high-fat diet consumption increases body weight and body adiposity and alters brain stem taste information processing in rats","volume":"47","author":"Kovacs","year":"2022","journal-title":"Chem. Senses"},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Bieghs, V., Verheyen, F., van Gorp, P.J., Hendrikx, T., Wouters, K., Lutjohann, D., Gijbels, M.J., Febbraio, M., Binder, C.J., and Hofker, M.H. (2012). Internalization of modified lipids by CD36 and SR-A leads to hepatic inflammation and lysosomal cholesterol storage in Kupffer cells. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0034378"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1626","DOI":"10.1194\/jlr.M016246","article-title":"Dietary cholesterol exacerbates hepatic steatosis and inflammation in obese LDL receptor-deficient mice","volume":"52","author":"Subramanian","year":"2011","journal-title":"J. Lipid Res."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1590\/S0103-05822014000100010","article-title":"Metabolic syndrome and insulin resistance in obese adolescents","volume":"32","author":"Gobato","year":"2014","journal-title":"Rev. Paul. Pediatr. Orgao Of. Da Soc. Pediatr. Sao Paulo"},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Deusdar\u00e1, R., de Moura Souza, A., and Szklo, M. (2022). Association between Obesity, Overweight, Elevated Waist Circumference, and Insulin Resistance Markers among Brazilian Adolescent Students. Nutrients, 14.","DOI":"10.3390\/nu14173487"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1007\/s11906-018-0812-z","article-title":"The Global Epidemic of the Metabolic Syndrome","volume":"20","author":"Saklayen","year":"2018","journal-title":"Curr. Hypertens. Rep."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"2462","DOI":"10.1016\/j.psyneuen.2013.05.010","article-title":"Differential central pathology and cognitive impairment in pre-diabetic and diabetic mice","volume":"38","author":"Ortiz","year":"2013","journal-title":"Psychoneuroendocrinology"},{"key":"ref_33","first-page":"e56672","article-title":"Study of In Vivo Glucose Metabolism in High-fat Diet-fed Mice Using Oral Glucose Tolerance Test (OGTT) and Insulin Tolerance Test (ITT)","volume":"131","author":"Nagy","year":"2018","journal-title":"J. Vis. Exp. JoVE"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1016\/j.brainresprot.2005.08.001","article-title":"Episodic-like memory in mice: Simultaneous assessment of object, place and temporal order memory","volume":"16","author":"Dere","year":"2005","journal-title":"Brain Res. Brain Res. Protoc."},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Yoshizaki, K., Asai, M., and Hara, T. (2020). High-Fat Diet Enhances Working Memory in the Y-Maze Test in Male C57BL\/6J Mice with Less Anxiety in the Elevated Plus Maze Test. Nutrients, 12.","DOI":"10.3390\/nu12072036"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"1011","DOI":"10.1002\/gps.4886","article-title":"Memory complaints in amnestic Mild Cognitive Impairment: More prospective or retrospective?","volume":"33","author":"Felgueiras","year":"2018","journal-title":"Int. J. Geriatr. Psychiatry"},{"key":"ref_37","first-page":"613","article-title":"Memory dysfunction","volume":"21","author":"Matthews","year":"2015","journal-title":"Contin. (Minneap. Minn.)"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"68","DOI":"10.1016\/S1474-4422(20)30412-9","article-title":"APOE and Alzheimer\u2019s disease: Advances in genetics, pathophysiology, and therapeutic approaches","volume":"20","author":"Das","year":"2021","journal-title":"Lancet Neurol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"401","DOI":"10.1038\/s41593-018-0332-9","article-title":"Mitophagy inhibits amyloid-\u03b2 and tau pathology and reverses cognitive deficits in models of Alzheimer\u2019s disease","volume":"22","author":"Fang","year":"2019","journal-title":"Nat. Neurosci."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"318","DOI":"10.1159\/000519452","article-title":"Evaluation of High Cholesterol and Risk of Dementia and Cognitive Decline in Older Adults Using Individual Patient Meta-Analysis","volume":"50","author":"Peters","year":"2021","journal-title":"Dement. Geriatr. Cogn. Disord."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"101043","DOI":"10.1016\/j.arr.2020.101043","article-title":"Blood fatty acids in Alzheimer\u2019s disease and mild cognitive impairment: A meta-analysis and systematic review","volume":"60","author":"Hosseini","year":"2020","journal-title":"Ageing Res. Rev."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"691","DOI":"10.3233\/JAD-2012-110629","article-title":"Plasma and brain fatty acid profiles in mild cognitive impairment and Alzheimer\u2019s disease","volume":"29","author":"Cunnane","year":"2012","journal-title":"J. Alzheimer\u2019s Dis. JAD"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1016\/j.psyneuen.2014.06.005","article-title":"Prediabetes-induced vascular alterations exacerbate central pathology in APPswe\/PS1dE9 mice","volume":"48","year":"2014","journal-title":"Psychoneuroendocrinology"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"1377","DOI":"10.1093\/jn\/nxz075","article-title":"Edible Mushrooms Reduce Atherosclerosis in Ldlr\u2212\/\u2212 Mice Fed a High-Fat Diet","volume":"149","author":"Kim","year":"2019","journal-title":"J. Nutr."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"4730","DOI":"10.1016\/j.clnu.2021.06.017","article-title":"Intra-pancreatic fat deposition as a modifier of the relationship between habitual dietary fat intake and insulin resistance","volume":"40","author":"Ko","year":"2021","journal-title":"Clin. Nutr."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"243","DOI":"10.5603\/EP.a2021.0037","article-title":"Insulin resistance in metabolic syndrome depending on the occurrence of its components","volume":"72","author":"Gierach","year":"2021","journal-title":"Endokrynol. Pol."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"E1373","DOI":"10.1152\/ajpendo.00500.2011","article-title":"Increased A\u03b2 production prompts the onset of glucose intolerance and insulin resistance","volume":"302","author":"Perdomo","year":"2012","journal-title":"Am. J. Physiol. Endocrinol. Metab."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"1220","DOI":"10.2741\/4640","article-title":"Modified low-density lipoproteins as biomarkers in diabetes and metabolic syndrome","volume":"23","author":"Benitez","year":"2018","journal-title":"Front. Biosci. (Landmark Ed.)"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"1453","DOI":"10.1172\/JCI134165","article-title":"Insulin resistance drives hepatic de novo lipogenesis in nonalcoholic fatty liver disease","volume":"130","author":"Smith","year":"2020","journal-title":"J. Clin. Investig."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"2905","DOI":"10.2337\/diabetes.52.12.2905","article-title":"Hepatic Akt activation induces marked hypoglycemia, hepatomegaly, and hypertriglyceridemia with sterol regulatory element binding protein involvement","volume":"52","author":"Ono","year":"2003","journal-title":"Diabetes"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"799","DOI":"10.1038\/414799a","article-title":"Insulin signalling and the regulation of glucose and lipid metabolism","volume":"414","author":"Saltiel","year":"2001","journal-title":"Nature"},{"key":"ref_52","doi-asserted-by":"crossref","unstructured":"Cignarelli, A., Genchi, V.A., Perrini, S., Natalicchio, A., Laviola, L., and Giorgino, F. (2019). Insulin and Insulin Receptors in Adipose Tissue Development. Int. J. Mol. Sci., 20.","DOI":"10.3390\/ijms20030759"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"111315","DOI":"10.1016\/j.biopha.2021.111315","article-title":"Adipose tissue and insulin resistance in obese","volume":"137","author":"Ahmed","year":"2021","journal-title":"Biomed. Pharmacother. Biomed. Pharmacother."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"2496","DOI":"10.2337\/db10-1536","article-title":"Obesity-associated hepatosteatosis and impairment of glucose homeostasis are attenuated by haptoglobin deficiency","volume":"60","author":"Lisi","year":"2011","journal-title":"Diabetes"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"e2439","DOI":"10.6061\/clinics\/2021\/e2439","article-title":"Fatty Pancreas: Disease or Finding?","volume":"76","author":"Silva","year":"2021","journal-title":"Clinics"},{"key":"ref_56","doi-asserted-by":"crossref","unstructured":"Kouvari, M., D\u2019Cunha, N.M., Travica, N., Sergi, D., Zec, M., Marx, W., and Naumovski, N. (2022). Metabolic Syndrome, Cognitive Impairment and the Role of Diet: A Narrative Review. Nutrients, 14.","DOI":"10.3390\/nu14020333"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"1149","DOI":"10.1007\/s00127-018-1581-3","article-title":"Mild cognitive impairment and progression to dementia in people with diabetes, prediabetes and metabolic syndrome: A systematic review and meta-analysis","volume":"53","author":"Pal","year":"2018","journal-title":"Soc. Psychiatry Psychiatr. Epidemiol."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"599","DOI":"10.1017\/S1355617704104165","article-title":"Type 2 diabetes mellitus contributes to cognitive decline in old age: A longitudinal population-based study","volume":"10","author":"Hassing","year":"2004","journal-title":"J. Int. Neuropsychol. Soc. JINS"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"1069","DOI":"10.3233\/JAD-160266","article-title":"Early Cognitive Deficits in Type 2 Diabetes: A Population-Based Study","volume":"53","author":"Marseglia","year":"2016","journal-title":"J. Alzheimer\u2019s Dis. JAD"},{"key":"ref_60","doi-asserted-by":"crossref","unstructured":"Nasiri, M., Moayedfar, S., Purmohammad, M., and Ghasisin, L. (2022). Investigating sentence processing and working memory in patients with mild Alzheimer and elderly people. PLoS ONE, 17.","DOI":"10.1371\/journal.pone.0266552"},{"key":"ref_61","doi-asserted-by":"crossref","unstructured":"Chatzikostopoulos, A., Moraitou, D., Tsolaki, M., Masoura, E., Papantoniou, G., Sofologi, M., Papaliagkas, V., Kougioumtzis, G., and Papatzikis, E. (2022). Episodic Memory in Amnestic Mild Cognitive Impairment (aMCI) and Alzheimer\u2019s Disease Dementia (ADD): Using the \u201cDoors and People\u201d Tool to Differentiate between Early aMCI-Late aMCI-Mild ADD Diagnostic Groups. Diagnostics, 12.","DOI":"10.3390\/diagnostics12071768"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1016\/j.rcpeng.2020.09.005","article-title":"Comparative study of the word capacity and episodic memory of patients with degenerative dementia","volume":"51","author":"Custodio","year":"2022","journal-title":"Rev. Colomb. Psiquiatr. (Engl. Ed.)"},{"key":"ref_63","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\/\u2212 and C57BL\/6 mice fed a western diet. PLoS ONE, 13.","DOI":"10.1371\/journal.pone.0191909"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1016\/j.exger.2015.03.010","article-title":"Hypercholesterolemia and neurodegeneration. Comparison of hippocampal phenotypes in LDLr knockout and APPswe\/PS1dE9 mice","volume":"65","author":"Ettcheto","year":"2015","journal-title":"Exp. Gerontol."},{"key":"ref_65","first-page":"97","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. Alzheimer\u2019s Dis. JAD"},{"key":"ref_66","doi-asserted-by":"crossref","unstructured":"Garcia-Morales, V., Gonzalez-Acedo, A., Melguizo-Rodriguez, L., Pardo-Moreno, T., Costela-Ruiz, V.J., Montiel-Troya, M., and Ramos-Rodriguez, J.J. (2021). Current Understanding of the Physiopathology, Diagnosis and Therapeutic Approach to Alzheimer\u2019s Disease. Biomedicines, 9.","DOI":"10.3390\/biomedicines9121910"},{"key":"ref_67","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_68","doi-asserted-by":"crossref","first-page":"408","DOI":"10.1016\/j.mcn.2010.08.001","article-title":"Hypercholesterolemia in rats impairs the cholinergic system and leads to memory deficits","volume":"45","author":"Ullrich","year":"2010","journal-title":"Mol. Cell. Neurosci."},{"key":"ref_69","first-page":"43","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. Alzheimer\u2019s Dis. JAD"},{"key":"ref_70","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_71","doi-asserted-by":"crossref","first-page":"101594","DOI":"10.1016\/j.smim.2022.101594","article-title":"APOE mediated neuroinflammation and neurodegeneration in Alzheimer\u2019s disease","volume":"59","author":"Parhizkar","year":"2022","journal-title":"Semin. Immunol."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"R170","DOI":"10.1016\/j.cub.2018.01.004","article-title":"Mitophagy and Quality Control Mechanisms in Mitochondrial Maintenance","volume":"28","author":"Pickles","year":"2018","journal-title":"Curr. Biol. CB"},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"151","DOI":"10.1016\/j.tins.2017.01.002","article-title":"Mitophagy and Alzheimer\u2019s Disease: Cellular and Molecular Mechanisms","volume":"40","author":"Kerr","year":"2017","journal-title":"Trends Neurosci."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"345","DOI":"10.1038\/nrn3961","article-title":"Compromised autophagy and neurodegenerative diseases","volume":"16","author":"Menzies","year":"2015","journal-title":"Nat. Rev. Neurosci."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"24","DOI":"10.3389\/fncel.2016.00024","article-title":"Alterations in Mitochondrial Quality Control in Alzheimer\u2019s Disease","volume":"10","author":"Cai","year":"2016","journal-title":"Front. Cell. Neurosci."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1016\/j.arr.2014.12.011","article-title":"Lifelong brain health is a lifelong challenge: From evolutionary principles to empirical evidence","volume":"20","author":"Mattson","year":"2015","journal-title":"Ageing Res. Rev."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"1250","DOI":"10.1038\/ncomms2238","article-title":"Involvement of PGC-1alpha in the formation and maintenance of neuronal dendritic spines","volume":"3","author":"Cheng","year":"2012","journal-title":"Nat. Commun."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"434","DOI":"10.1097\/MOL.0b013e32833ded6a","article-title":"Atherosclerotic lesions in mouse and man: Is it the same disease?","volume":"21","author":"Bentzon","year":"2010","journal-title":"Curr. Opin. Lipidol."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"2336","DOI":"10.1161\/01.ATV.20.11.2336","article-title":"Genetic modifiers of atherosclerosis in mice","volume":"20","author":"Knowles","year":"2000","journal-title":"Arterioscler. Thromb. Vasc. Biol."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1016\/j.bbr.2016.05.029","article-title":"Is there an association between hypercholesterolemia and depression? Behavioral evidence from the LDLr(\u2212\/\u2212) mouse experimental model","volume":"311","author":"Engel","year":"2016","journal-title":"Behav. Brain Res."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"1706","DOI":"10.1161\/ATVBAHA.107.142570","article-title":"Mouse models for atherosclerosis and pharmaceutical modifiers","volume":"27","author":"Zadelaar","year":"2007","journal-title":"Arterioscler. Thromb. Vasc. Biol."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"2685","DOI":"10.1007\/s12035-015-9311-2","article-title":"Increased Spontaneous Central Bleeding and Cognition Impairment in APP\/PS1 Mice with Poorly Controlled Diabetes Mellitus","volume":"53","year":"2016","journal-title":"Mol. Neurobiol."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"214","DOI":"10.1016\/j.nlm.2005.07.002","article-title":"Integrated memory for objects, places, and temporal order: Evidence for episodic-like memory in mice","volume":"84","author":"Dere","year":"2005","journal-title":"Neurobiol. Learn. Mem."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1146\/annurev.psych.53.100901.135114","article-title":"Episodic memory: From mind to brain","volume":"53","author":"Tulving","year":"2002","journal-title":"Annu. Rev. Psychol."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"2077","DOI":"10.1093\/clinchem\/28.10.2077","article-title":"Serum triglycerides determined colorimetrically with an enzyme that produces hydrogen peroxide","volume":"28","author":"Fossati","year":"1982","journal-title":"Clin. Chem."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/24\/9\/8042\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T19:26:04Z","timestamp":1760124364000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/24\/9\/8042"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,4,28]]},"references-count":85,"journal-issue":{"issue":"9","published-online":{"date-parts":[[2023,5]]}},"alternative-id":["ijms24098042"],"URL":"https:\/\/doi.org\/10.3390\/ijms24098042","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,4,28]]}}}