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Early detection of AD remains a challenge, as clinical manifestations only emerge in the advanced stages, limiting therapeutic interventions. Minimally invasive biomarkers are essential for early identification and monitoring of disease progression. This study aims to evaluate the sensitivity of the relationship between serum oligoelement levels as biomarkers and the monitoring of AD progression in the 3xTg-AD model. Transgenic 3xTg-AD mice and C57BL\/6 controls were evaluated over 12 months through serum oligoelement quantification using inductively coupled plasma mass spectrometry (ICP-MS), A\u03b2 deposition via immunohistochemistry, and cognitive assessments using memory tests (Morris water maze and novel object recognition test), as well as spontaneous locomotion analysis using the open field test. The results demonstrated that oligoelements (copper, zinc, and selenium) were sensitive in detecting alterations in the AD group, preceding cognitive and motor deficits. Immunohistochemistry was performed for qualitative purposes, confirming the presence of \u03b2-amyloid in the CNS of transgenic animals. Up to the third month, labeling was moderate and restricted to neuronal cell bodies; from the fifth month onward, evident extracellular deposits emerged. Behavioral assessment indicated impairments in spatial and episodic memory, as well as altered locomotor patterns in AD mice. These findings reinforce that oligoelement variations may be associated with neurodegenerative processes, including oxidative stress and synaptic dysfunction. Thus, oligoelement analysis emerges as a promising approach for the early diagnosis of AD and the monitoring of disease progression, potentially contributing to the development of new therapeutic strategies.<\/jats:p>","DOI":"10.3390\/ijms26083657","type":"journal-article","created":{"date-parts":[[2025,4,14]],"date-time":"2025-04-14T06:18:36Z","timestamp":1744611516000},"page":"3657","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Longitudinal Evaluation of the Detection Potential of Serum Oligoelements Cu, Se and Zn for the Diagnosis of Alzheimer\u2019s Disease in the 3xTg-AD Animal Model"],"prefix":"10.3390","volume":"26","author":[{"given":"Olivia F. M.","family":"Dias","sequence":"first","affiliation":[{"name":"Hospital Israelita Albert Einstein, S\u00e3o Paulo 05652-000, SP, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4523-1753","authenticated-orcid":false,"given":"Nicole M. E.","family":"Valle","sequence":"additional","affiliation":[{"name":"Hospital Israelita Albert Einstein, S\u00e3o Paulo 05652-000, SP, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Javier B.","family":"Mamani","sequence":"additional","affiliation":[{"name":"Hospital Israelita Albert Einstein, S\u00e3o Paulo 05652-000, SP, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cicero J. S.","family":"Costa","sequence":"additional","affiliation":[{"name":"Hospital Israelita Albert Einstein, S\u00e3o Paulo 05652-000, SP, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3570-0827","authenticated-orcid":false,"given":"Arielly H.","family":"Alves","sequence":"additional","affiliation":[{"name":"Hospital Israelita Albert Einstein, S\u00e3o Paulo 05652-000, SP, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7226-1694","authenticated-orcid":false,"given":"Fernando A.","family":"Oliveira","sequence":"additional","affiliation":[{"name":"Hospital Israelita Albert Einstein, S\u00e3o Paulo 05652-000, SP, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2011-0373","authenticated-orcid":false,"given":"Gabriel N. A.","family":"Rego","sequence":"additional","affiliation":[{"name":"Hospital Israelita Albert Einstein, S\u00e3o Paulo 05652-000, SP, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-2924-4262","authenticated-orcid":false,"given":"Marta C. S.","family":"Galanciak","sequence":"additional","affiliation":[{"name":"Hospital Israelita Albert Einstein, S\u00e3o Paulo 05652-000, SP, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-8856-9654","authenticated-orcid":false,"given":"Keithy","family":"Felix","sequence":"additional","affiliation":[{"name":"Hospital Israelita Albert Einstein, S\u00e3o Paulo 05652-000, SP, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1502-9215","authenticated-orcid":false,"given":"Mariana P.","family":"Nucci","sequence":"additional","affiliation":[{"name":"LIM44\u2014Hospital das Cl\u00ednicas da Faculdade Medicina da Universidade de S\u00e3o Paulo, S\u00e3o Paulo 05403-000, SP, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3910-0047","authenticated-orcid":false,"given":"Lionel F.","family":"Gamarra","sequence":"additional","affiliation":[{"name":"Hospital Israelita Albert Einstein, S\u00e3o Paulo 05652-000, SP, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,4,12]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"692","DOI":"10.1002\/kjm2.12870","article-title":"Advances in blood biomarkers for Alzheimer disease (AD): A review","volume":"40","author":"Assfaw","year":"2024","journal-title":"Kaohsiung J. Med. Sci."},{"key":"ref_2","unstructured":"WHO (2023). Global Status Report on the Public Health Response to Dementia, World Health Organization."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/s13293-023-00536-5","article-title":"Sex differences in metabolic phenotype and hypothalamic inflammation in the 3xTg-AD mouse model of Alzheimer\u2019s disease","volume":"14","author":"Robison","year":"2023","journal-title":"Biol. Sex Differ."},{"key":"ref_4","unstructured":"GBD (2021). The Lancet Neurology, Global Burden of Disease Study."},{"key":"ref_5","unstructured":"PAHO (2021). The Economic Impact of Alzheimer\u2019s Disease in Latin America and the Caribbean, Pan American Health Organization."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"243","DOI":"10.1007\/s12031-015-0665-8","article-title":"Liver X Receptor Agonist Modifies the DNA Methylation Profile of Synapse and Neurogenesis-Related Genes in the Triple Transgenic Mouse Model of Alzheimer\u2019s Disease","volume":"58","author":"Restrepo","year":"2016","journal-title":"J. Mol. Neurosci."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"535","DOI":"10.1016\/j.jalz.2018.02.018","article-title":"NIA-AA Research Framework: Toward a biological definition of Alzheimer\u2019s disease","volume":"14","author":"Jack","year":"2018","journal-title":"Alzheimer\u2019s Dement."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"811","DOI":"10.1007\/s00580-024-03603-4","article-title":"Pathophysiology of Alzheimer\u2019s disease: An insight into the genetic factors, hypotheses, redox imbalance, and antioxidant intervention","volume":"33","author":"Abdulkadir","year":"2024","journal-title":"Comp. Clin. Pathol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"954","DOI":"10.1038\/s41591-021-01382-x","article-title":"Biomarkers for neurodegenerative diseases","volume":"27","author":"Hansson","year":"2021","journal-title":"Nat. Med."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"280","DOI":"10.1016\/j.jalz.2011.03.003","article-title":"Toward defining the preclinical stages of Alzheimer\u2019s disease: Recommendations from the National Institute on Aging-Alzheimer\u2019s Association workgroups on diagnostic guidelines for Alzheimer\u2019s disease","volume":"7","author":"Sperling","year":"2011","journal-title":"Alzheimers Dement."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"772","DOI":"10.1001\/jama.2020.12134","article-title":"Discriminative accuracy of plasma phospho-tau217 for Alzheimer disease vs other neurodegenerative disorders","volume":"324","author":"Palmqvist","year":"2020","journal-title":"JAMA"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"557","DOI":"10.1001\/jamaneurol.2016.6117","article-title":"Association of Plasma Neurofilament Light with Neurodegeneration in Patients with Alzheimer Disease","volume":"74","author":"Mattsson","year":"2017","journal-title":"JAMA Neurol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"3975","DOI":"10.1021\/acschemneuro.3c00641","article-title":"Blood Biomarkers in Alzheimer\u2019s Disease","volume":"14","author":"Mandal","year":"2023","journal-title":"ACS Chem. Neurosci."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1321","DOI":"10.1039\/c2mt20162c","article-title":"Characterisation of element profile changes induced by long-term dietary supplementation of zinc in the brain and cerebellum of 3xTg-AD mice by alternated cool and normal plasma ICP-MS","volume":"4","author":"Ciavardelli","year":"2012","journal-title":"Metallomics"},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Squitti, R., Ventriglia, M., Simonelli, I., Bonvicini, C., Costa, A., Perini, G., Binetti, G., Benussi, L., Ghidoni, R., and Koch, G. (2021). Copper Imbalance in Alzheimer\u2019s Disease: Meta-Analysis of Serum, Plasma, and Brain Specimens, and Replication Study Evaluating ATP7B Gene Variants. Biomolecules, 11.","DOI":"10.3390\/biom11070960"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"S141","DOI":"10.3233\/JAD-240140","article-title":"Targeting Metals in Alzheimer\u2019s Disease: An Update","volume":"101","author":"Du","year":"2024","journal-title":"J. Alzheimer\u2019s Dis."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"663","DOI":"10.1016\/j.talanta.2019.05.098","article-title":"Determination of Zn, Cu and Fe in human patients\u2019 serum using micro-sampling ICP-MS and sample dilution","volume":"204","author":"Abduljabbar","year":"2019","journal-title":"Talanta"},{"key":"ref_18","first-page":"1","article-title":"Age, sex and Alzheimer\u2019s disease: A longitudinal study of 3xTg-AD mice reveals sex-specific disease trajectories and inflammatory responses mirrored in postmortem brains from Alzheimer\u2019s patients","volume":"16","author":"Barber","year":"2024","journal-title":"Alzheimer\u2019s Res. Ther."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1038\/s41598-021-99025-1","article-title":"Dopaminergic dysfunction in the 3xTg-AD mice model of Alzheimer\u2019s disease","volume":"11","author":"Gloria","year":"2021","journal-title":"Sci. Rep."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"409","DOI":"10.1016\/S0896-6273(03)00434-3","article-title":"Triple-transgenic model of Alzheimer\u2019s disease with plaques and tangles: Intracellular A\u03b2 and synaptic dysfunction","volume":"39","author":"Oddo","year":"2003","journal-title":"Neuron"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"751","DOI":"10.1523\/JNEUROSCI.4800-06.2007","article-title":"Learning decreases A\u03b2*56 and tau pathology and ameliorates behavioral decline in 3xTg-AD mice","volume":"27","author":"Billings","year":"2007","journal-title":"J. Neurosci."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"149","DOI":"10.1016\/j.brainres.2010.06.011","article-title":"Characterization of the 3xTg-AD mouse model of Alzheimer\u2019s disease: Part 2. Behavioral and cognitive changes","volume":"1348","author":"Sterniczuk","year":"2010","journal-title":"Brain Res."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1016\/j.bbr.2015.04.012","article-title":"Early detection of cognitive deficits in the 3xTg-AD mouse model of Alzheimer\u2019s disease","volume":"289","author":"Stover","year":"2015","journal-title":"Behav. Brain Res."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1007\/s10339-011-0430-z","article-title":"The novel object recognition memory: Neurobiology, test procedure, and its modifications","volume":"13","author":"Antunes","year":"2012","journal-title":"Cogn. Process."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"254","DOI":"10.1016\/j.bbr.2010.05.034","article-title":"Caffeine prevents disruption of memory consolidation in the inhibitory avoidance and novel object recognition tasks by scopolamine in adult mice","volume":"214","author":"Botton","year":"2010","journal-title":"Behav. Brain Res."},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Babi\u0107 Leko, M., Langer Horvat, L., \u0160pani\u0107 Popova\u010dki, E., Zub\u010di\u0107, K., Hof, P.R., and \u0160imi\u0107, G. (2023). Metals in Alzheimer\u2019s Disease. Biomedicines, 11.","DOI":"10.3390\/biomedicines11041161"},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Socha, K., Klimiuk, K., Naliwajko, S.K., Soroczy\u0144ska, J., Pu\u015bcion-Jakubik, A., Markiewicz-\u017bukowska, R., and Kochanowicz, J. (2021). Dietary Habits, Selenium, Copper, Zinc and Total Antioxidant Status in Serum in Relation to Cognitive Functions of Patients with Alzheimer\u2019s Disease. Nutrients, 13.","DOI":"10.3390\/nu13020287"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"565","DOI":"10.3233\/JAD-143108","article-title":"Serum Iron, Zinc, and Copper Levels in Patients with Alzheimer\u2019s Disease: A Replication Study and Meta-Analyses","volume":"47","author":"Wang","year":"2015","journal-title":"J. Alzheimer\u2019s Dis."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"175","DOI":"10.3233\/JAD-2010-101473","article-title":"Copper in Alzheimer\u2019s disease: A meta-analysis of serum, plasma, and cerebrospinal fluid studies","volume":"24","author":"Bucossi","year":"2011","journal-title":"J. Alzheimer\u2019s Dis."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"353","DOI":"10.1177\/1533317517709549","article-title":"Oxidative Stress Markers and Metal Ions are Correlated with Cognitive Function in Alzheimer\u2019s Disease","volume":"32","author":"Pu","year":"2017","journal-title":"Am. J. Alzheimer\u2019s Dis. Other Dementiasr"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"181","DOI":"10.1016\/j.jtemb.2017.11.005","article-title":"Copper dyshomeostasis in Wilson disease and Alzheimer\u2019s disease as shown by serum and urine copper indicators","volume":"45","author":"Squitti","year":"2018","journal-title":"J. Trace Elem. Med. Biol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"185","DOI":"10.1007\/s12011-017-1042-y","article-title":"The Relationship Between Copper, Iron, and Selenium Levels and Alzheimer Disease","volume":"181","author":"Vaz","year":"2018","journal-title":"Biol. Trace Elem. Res."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"3245","DOI":"10.1007\/s11033-021-06386-x","article-title":"Metals toxicity and its correlation with the gene expression in Alzheimer\u2019s disease","volume":"48","author":"Yadav","year":"2021","journal-title":"Mol. Biol. Rep."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"674","DOI":"10.2174\/1567205019666220913114154","article-title":"Trace Element Concentration and Cognitive Dysfunction in Elderly Residents in Birjand","volume":"19","author":"Toba","year":"2022","journal-title":"Curr. Alzheimer Res."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"120782","DOI":"10.1016\/j.envpol.2022.120782","article-title":"Trace elements and Alzheimer dementia in population-based studies: A bibliometric and meta-analysis","volume":"318","author":"Li","year":"2023","journal-title":"Environ. Pollut."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"292","DOI":"10.1039\/C3MT00301A","article-title":"Characterization of metal profiles in serum during the progression of Alzheimer\u2019s disease","volume":"6","year":"2014","journal-title":"Metallomics"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"261","DOI":"10.3233\/JAD-131892","article-title":"Differences in nutritional status between very mild Alzheimer\u2019s disease patients and healthy controls","volume":"41","author":"Verhey","year":"2014","journal-title":"J. Alzheimer\u2019s Dis."},{"key":"ref_38","doi-asserted-by":"crossref","unstructured":"Paglia, G., Miedico, O., Cristofano, A., Vitale, M., Angiolillo, A., Chiaravalle, A.E., Corso, G., and Di Costanzo, A. (2016). Distinctive Pattern of Serum Elements During the Progression of Alzheimer\u2019s Disease. Sci. Rep., 6.","DOI":"10.1038\/srep22769"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"1049","DOI":"10.33549\/physiolres.933601","article-title":"Relation of plasma selenium and lipid peroxidation end products in patients with Alzheimer\u2019s disease","volume":"66","author":"Chmatalova","year":"2017","journal-title":"Physiol. Res."},{"key":"ref_40","doi-asserted-by":"crossref","unstructured":"Strumylaite, L., Kregzdyte, R., Kucikiene, O., Baranauskiene, D., Simakauskiene, V., Naginiene, R., Damuleviciene, G., Lesauskaite, V., and Zemaitiene, R. (2022). Alzheimer\u2019s Disease Association with Metals and Metalloids Concentration in Blood and Urine. Int. J. Environ. Res. Public Health, 19.","DOI":"10.3390\/ijerph19127309"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"173","DOI":"10.1007\/s10534-009-9277-5","article-title":"Serum zinc is decreased in Alzheimer\u2019s disease and serum arsenic correlates positively with cognitive ability","volume":"23","author":"Baum","year":"2010","journal-title":"BioMetals"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"343","DOI":"10.3233\/JAD-215063","article-title":"Adiponectin Ameliorates Cognitive Behaviors and In Vivo Synaptic Plasticity Impairments in 3xc Mice","volume":"85","author":"Yan","year":"2022","journal-title":"J. Alzheimer\u2019s Dis."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1038\/4789","article-title":"Increased vulnerability of hippocampal neurons to excitotoxic necrosis in presenilin-1 mutant knock-in mice","volume":"5","author":"Guo","year":"1999","journal-title":"Nat Med"},{"key":"ref_44","doi-asserted-by":"crossref","unstructured":"Mastrangelo, M.A., and Bowers, W.J. (2008). Detailed immunohistochemical characterization of temporal and spatial progression of Alzheimer\u2019s disease-related pathologies in male triple-transgenic mice. BMC Neurosci., 9.","DOI":"10.1186\/1471-2202-9-81"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"897","DOI":"10.3233\/JAD-2011-111529","article-title":"A\u03b2PP Accumulation and\/or Intraneuronal Amyloid-\u03b2 Accumulation? The 3xTg-AD Mouse Model Revisited","volume":"28","author":"Wirths","year":"2012","journal-title":"J. Alzheimer\u2019s Dis."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"1063","DOI":"10.1016\/j.neurobiolaging.2003.08.012","article-title":"Amyloid deposition precedes tangle formation in a triple transgenic model of Alzheimer\u2019s disease","volume":"24","author":"Oddo","year":"2003","journal-title":"Neurobiol. Aging"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"115","DOI":"10.1186\/s13195-018-0441-4","article-title":"Active full-length DNA A\u03b242 immunization in 3xTg-AD mice reduces not only amyloid deposition but also tau pathology","volume":"10","author":"Rosenberg","year":"2018","journal-title":"Alzheimer\u2019s Res. Ther."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"1341","DOI":"10.1038\/s41593-018-0238-6","article-title":"Propagation and spread of pathogenic protein assemblies in neurodegenerative diseases","volume":"21","author":"Jucker","year":"2018","journal-title":"Nat. Neurosci."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1016\/j.neurobiolaging.2023.01.008","article-title":"Orexin-A aggravates cognitive deficits in 3xTg-AD mice by exacerbating synaptic plasticity impairment and affecting amyloid \u03b2 metabolism","volume":"124","author":"Li","year":"2023","journal-title":"Neurobiol. Aging"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"154962","DOI":"10.1016\/j.phymed.2023.154962","article-title":"Berberine ameliorates iron levels and ferroptosis in the brain of 3 \u00d7 Tg-AD mice","volume":"118","author":"Li","year":"2023","journal-title":"Phytomedicine"},{"key":"ref_51","doi-asserted-by":"crossref","unstructured":"Son, H.J., Jeong, Y.J., Yoon, H.J., Lee, S.Y., Choi, G.-E., Park, J.-A., Kim, M.H., Lee, K.C., Lee, Y.J., and Kim, M.K. (2018). Assessment of brain beta-amyloid deposition in transgenic mouse models of Alzheimer\u2019s disease with PET imaging agents 18F-flutemetamol and 18F-florbetaben. BMC Neurosci., 19.","DOI":"10.1186\/s12868-018-0447-7"},{"key":"ref_52","first-page":"55718","article-title":"Novel Object Recognition Test for the Investigation of Learning and Memory in Mice","volume":"126","author":"Lueptow","year":"2017","journal-title":"J. Vis. Exp."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"453","DOI":"10.1101\/lm.026070.112","article-title":"Restoration of dopamine release deficits during object recognition memory acquisition attenuates cognitive impairment in a triple transgenic mice model of Alzheimer\u2019s disease","volume":"19","author":"McGaugh","year":"2012","journal-title":"Learn. Mem."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"1219","DOI":"10.1016\/j.omtn.2020.01.010","article-title":"miRNA-31 Improves Cognition and Abolishes Amyloid-\u03b2 Pathology by Targeting APP and BACE1 in an Animal Model of Alzheimer\u2019s Disease","volume":"19","author":"Carmona","year":"2020","journal-title":"Mol. Ther. Nucleic Acids"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"369","DOI":"10.1515\/REVNEURO.2003.14.4.369","article-title":"Neurobehavioral characteristics of mice with modified intermediate filament genes","volume":"14","author":"Lalonde","year":"2003","journal-title":"Rev. Neurosci."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"915","DOI":"10.1111\/jnc.13195","article-title":"Short-term modern life-like stress exacerbates A\u03b2-pathology and synapse loss in 3xTg-AD mice","volume":"134","author":"Chen","year":"2015","journal-title":"J. Neurochem."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"54","DOI":"10.1186\/s13195-018-0384-9","article-title":"Immunotherapy to improve cognition and reduce pathological species in an Alzheimer\u2019s disease mouse model","volume":"10","author":"Herline","year":"2018","journal-title":"Alzheimer\u2019s Res. Ther."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"473","DOI":"10.1111\/pcn.13706","article-title":"Cholesterol profiling reveals 7\u03b2-hydroxycholesterol as a pathologically relevant peripheral biomarker of Alzheimer\u2019s disease","volume":"78","author":"Ha","year":"2024","journal-title":"Psychiatry Clin. Neurosci."},{"key":"ref_59","doi-asserted-by":"crossref","unstructured":"Dionisio-Santos, D.A., Karaahmet, B., Belcher, E.K., Owlett, L.D., Trojanczyk, L.A., Olschowka, J.A., and O\u2019Banion, M.K. (2021). Evaluating Effects of Glatiramer Acetate Treatment on Amyloid Deposition and Tau Phosphorylation in the 3xTg Mouse Model of Alzheimer\u2019s Disease. Front. Neurosci., 15.","DOI":"10.3389\/fnins.2021.758677"},{"key":"ref_60","doi-asserted-by":"crossref","unstructured":"Mulder, C.K., Gerkema, M.P., and Van Der Zee, E.A. (2013). Circadian clocks and memory: Time-place learning. Front. Mol. Neurosci., 6.","DOI":"10.3389\/fnmol.2013.00008"},{"key":"ref_61","doi-asserted-by":"crossref","unstructured":"Castro-Alvarez, J.F., Alejandro Uribe-Arias, S., Kosik, K.S., and Cardona-G\u00f3mez, G.P. (2014). Long- and short-term CDK5 knockdown prevents spatial memory dysfunction and tau pathology of triple transgenic Alzheimer\u2019s mice. Front. Aging Neurosci., 6.","DOI":"10.3389\/fnagi.2014.00243"},{"key":"ref_62","doi-asserted-by":"crossref","unstructured":"Carvalho da Silva, A.M., Lemos, C., Silva, H.B., Ferreira, I.L., Tom\u00e9, A.R., Rego, A.C., and Cunha, R.A. (2022). Simultaneous Alteration of the Circadian Variation of Memory, Hippocampal Synaptic Plasticity, and Metabolism in a Triple Transgenic Mouse Model of Alzheimer\u2019s Disease. Front. Aging Neurosci., 14.","DOI":"10.3389\/fnagi.2022.835885"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"740","DOI":"10.1016\/j.neubiorev.2021.05.017","article-title":"Time-of-day as a critical biological variable","volume":"127","author":"Nelson","year":"2021","journal-title":"Neurosci. Biobehav. Rev."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/26\/8\/3657\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T17:13:21Z","timestamp":1760030001000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/26\/8\/3657"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,4,12]]},"references-count":63,"journal-issue":{"issue":"8","published-online":{"date-parts":[[2025,4]]}},"alternative-id":["ijms26083657"],"URL":"https:\/\/doi.org\/10.3390\/ijms26083657","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,4,12]]}}}