{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,27]],"date-time":"2026-02-27T18:38:45Z","timestamp":1772217525655,"version":"3.50.1"},"reference-count":146,"publisher":"MDPI AG","issue":"17","license":[{"start":{"date-parts":[[2024,8,31]],"date-time":"2024-08-31T00:00:00Z","timestamp":1725062400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Funda\u00e7\u00e3o para a Ci\u00eancia e Tecnologia","award":["(FCT)-PTDC\/MED-NEU\/2382\/2021"],"award-info":[{"award-number":["(FCT)-PTDC\/MED-NEU\/2382\/2021"]}]},{"name":"Funda\u00e7\u00e3o para a Ci\u00eancia e Tecnologia","award":["LISBOA-01-0145-FEDER-031395"],"award-info":[{"award-number":["LISBOA-01-0145-FEDER-031395"]}]},{"name":"Funda\u00e7\u00e3o para a Ci\u00eancia e Tecnologia","award":["HR21-00931"],"award-info":[{"award-number":["HR21-00931"]}]},{"name":"La Caixa Foundation-Luz\u00f3n Foundation","award":["(FCT)-PTDC\/MED-NEU\/2382\/2021"],"award-info":[{"award-number":["(FCT)-PTDC\/MED-NEU\/2382\/2021"]}]},{"name":"La Caixa Foundation-Luz\u00f3n Foundation","award":["LISBOA-01-0145-FEDER-031395"],"award-info":[{"award-number":["LISBOA-01-0145-FEDER-031395"]}]},{"name":"La Caixa Foundation-Luz\u00f3n Foundation","award":["HR21-00931"],"award-info":[{"award-number":["HR21-00931"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Alzheimer\u2019s disease (AD), the leading cause of dementia, is a multifactorial disease influenced by aging, genetics, and environmental factors. miRNAs are crucial regulators of gene expression and play significant roles in AD onset and progression. This exploratory study analyzed the expression levels of 28 genes and 5 miRNAs (miR-124-3p, miR-125b-5p, miR-21-5p, miR-146a-5p, and miR-155-5p) related to AD pathology and neuroimmune responses using RT-qPCR. Analyses were conducted in the prefrontal cortex (PFC) and the hippocampus (HPC) of the 5xFAD mouse AD model at 6 and 9 months old. Data highlighted upregulated genes encoding for glial fibrillary acidic protein (Gfap), triggering receptor expressed on myeloid cells (Trem2) and cystatin F (Cst7), in the 5xFAD mice at both regions and ages highlighting their roles as critical disease players and potential biomarkers. Overexpression of genes encoding for CCAAT enhancer-binding protein alpha (Cebpa) and myelin proteolipid protein (Plp) in the PFC, as well as for BCL2 apoptosis regulator (Bcl2) and purinergic receptor P2Y12 (P2yr12) in the HPC, together with upregulated microRNA(miR)-146a-5p in the PFC, prevailed in 9-month-old animals. miR-155 positively correlated with miR-146a and miR-21 in the PFC, and miR-125b positively correlated with miR-155, miR-21, while miR-146a in the HPC. Correlations between genes and miRNAs were dynamic, varying by genotype, region, and age, suggesting an intricate, disease-modulated interaction between miRNAs and target pathways. These findings contribute to our understanding of miRNAs as therapeutic targets for AD, given their multifaceted effects on neurons and glial cells.<\/jats:p>","DOI":"10.3390\/ijms25179475","type":"journal-article","created":{"date-parts":[[2024,9,3]],"date-time":"2024-09-03T09:56:42Z","timestamp":1725357402000},"page":"9475","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Spatiotemporal Dysregulation of Neuron\u2013Glia Related Genes and Pro-\/Anti-Inflammatory miRNAs in the 5xFAD Mouse Model of Alzheimer\u2019s Disease"],"prefix":"10.3390","volume":"25","author":[{"ORCID":"https:\/\/orcid.org\/0009-0008-0241-967X","authenticated-orcid":false,"given":"Marta","family":"Ianni","sequence":"first","affiliation":[{"name":"Instituto de Investiga\u00e7\u00e3o do Medicamento (iMed.ULisboa), Faculdade de Farm\u00e1cia da Universidade de Lisboa, 1649-003 Lisboa, Portugal"},{"name":"Dipartimento di Scienze della Vita, Universit\u00e0 degli Studi di Trieste, 34127 Trieste, Italy"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1417-2757","authenticated-orcid":false,"given":"Miriam","family":"Corraliza-Gomez","sequence":"additional","affiliation":[{"name":"Instituto de Investiga\u00e7\u00e3o do Medicamento (iMed.ULisboa), Faculdade de Farm\u00e1cia da Universidade de Lisboa, 1649-003 Lisboa, Portugal"},{"name":"Division of Physiology, School of Medicine, Universidad de Cadiz, 11003 Cadiz, Spain"},{"name":"Instituto de Investigaci\u00f3n e Innovaci\u00f3n Biom\u00e9dica de Cadiz (INIBICA), 11003 Cadiz, Spain"}]},{"given":"Tiago","family":"Costa-Coelho","sequence":"additional","affiliation":[{"name":"Instituto de Investiga\u00e7\u00e3o do Medicamento (iMed.ULisboa), Faculdade de Farm\u00e1cia da Universidade de Lisboa, 1649-003 Lisboa, Portugal"},{"name":"Instituto de Farmacologia e Neuroci\u00eancias, Faculdade de Medicina da Universidade de Lisboa, 1649-028 Lisboa, Portugal"},{"name":"Instituto de Medicina Molecular Jo\u00e3o Lobo Antunes, Faculdade de Medicina da Universidade de Lisboa, 1649-028 Lisboa, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5074-8154","authenticated-orcid":false,"given":"Mafalda","family":"Ferreira-Manso","sequence":"additional","affiliation":[{"name":"Instituto de Investiga\u00e7\u00e3o do Medicamento (iMed.ULisboa), Faculdade de Farm\u00e1cia da Universidade de Lisboa, 1649-003 Lisboa, Portugal"},{"name":"Instituto de Farmacologia e Neuroci\u00eancias, Faculdade de Medicina da Universidade de Lisboa, 1649-028 Lisboa, Portugal"},{"name":"Instituto de Medicina Molecular Jo\u00e3o Lobo Antunes, Faculdade de Medicina da Universidade de Lisboa, 1649-028 Lisboa, Portugal"}]},{"given":"Sara","family":"Inteiro-Oliveira","sequence":"additional","affiliation":[{"name":"Instituto de Farmacologia e Neuroci\u00eancias, Faculdade de Medicina da Universidade de Lisboa, 1649-028 Lisboa, Portugal"},{"name":"Instituto de Medicina Molecular Jo\u00e3o Lobo Antunes, Faculdade de Medicina da Universidade de Lisboa, 1649-028 Lisboa, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2100-1240","authenticated-orcid":false,"given":"Nuno","family":"Alem\u00e3n-Serrano","sequence":"additional","affiliation":[{"name":"Instituto de Farmacologia e Neuroci\u00eancias, Faculdade de Medicina da Universidade de Lisboa, 1649-028 Lisboa, Portugal"},{"name":"Instituto de Medicina Molecular Jo\u00e3o Lobo Antunes, Faculdade de Medicina da Universidade de Lisboa, 1649-028 Lisboa, Portugal"},{"name":"ULS Santa Maria, Centro Hospitalar Universit\u00e1rio Lisboa Norte, Centro Acad\u00e9mico de Medicina de Lisboa, 1649-028 Lisboa, Portugal"}]},{"given":"Ana M.","family":"Sebasti\u00e3o","sequence":"additional","affiliation":[{"name":"Instituto de Farmacologia e Neuroci\u00eancias, Faculdade de Medicina da Universidade de Lisboa, 1649-028 Lisboa, Portugal"},{"name":"Instituto de Medicina Molecular Jo\u00e3o Lobo Antunes, Faculdade de Medicina da Universidade de Lisboa, 1649-028 Lisboa, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5526-5362","authenticated-orcid":false,"given":"Gon\u00e7alo","family":"Garcia","sequence":"additional","affiliation":[{"name":"Instituto de Investiga\u00e7\u00e3o do Medicamento (iMed.ULisboa), Faculdade de Farm\u00e1cia da Universidade de Lisboa, 1649-003 Lisboa, Portugal"},{"name":"Department of Pharmaceutical Sciences and Medicines, Faculdade de Farm\u00e1cia da Universidade de Lisboa, 1649-003 Lisboa, Portugal"}]},{"given":"Maria Jos\u00e9","family":"Di\u00f3genes","sequence":"additional","affiliation":[{"name":"Instituto de Farmacologia e Neuroci\u00eancias, Faculdade de Medicina da Universidade de Lisboa, 1649-028 Lisboa, Portugal"},{"name":"Instituto de Medicina Molecular Jo\u00e3o Lobo Antunes, Faculdade de Medicina da Universidade de Lisboa, 1649-028 Lisboa, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3024-9777","authenticated-orcid":false,"given":"Dora","family":"Brites","sequence":"additional","affiliation":[{"name":"Instituto de Investiga\u00e7\u00e3o do Medicamento (iMed.ULisboa), Faculdade de Farm\u00e1cia da Universidade de Lisboa, 1649-003 Lisboa, Portugal"},{"name":"Department of Pharmaceutical Sciences and Medicines, Faculdade de Farm\u00e1cia da Universidade de Lisboa, 1649-003 Lisboa, Portugal"}]}],"member":"1968","published-online":{"date-parts":[[2024,8,31]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"8826","DOI":"10.1007\/s12035-018-1032-x","article-title":"MicroRNA Expression Levels Are Altered in the Cerebrospinal Fluid of Patients with Young-Onset Alzheimer\u2019s Disease","volume":"55","author":"McKeever","year":"2018","journal-title":"Mol. Neurobiol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"245","DOI":"10.1038\/s41582-024-00940-4","article-title":"Is Alzheimer disease a disease?","volume":"20","author":"Korczyn","year":"2024","journal-title":"Nat. Rev. Neurol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"e1837","DOI":"10.1212\/WNL.0000000000207770","article-title":"Eligibility for Anti-Amyloid Treatment in a Population-Based Study of Cognitive Aging","volume":"101","author":"Pittock","year":"2023","journal-title":"Neurology"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1038\/s41572-021-00269-y","article-title":"Alzheimer disease","volume":"7","author":"Knopman","year":"2021","journal-title":"Nat. Rev. Dis. Primers"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"e12802","DOI":"10.1111\/acel.12802","article-title":"Aging and Alzheimer\u2019s disease: Comparison and associations from molecular to system level","volume":"17","author":"Xia","year":"2018","journal-title":"Aging Cell"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1208","DOI":"10.1016\/j.neuron.2024.01.024","article-title":"Mechanisms of sex differences in Alzheimer\u2019s disease","volume":"112","author":"Torres","year":"2024","journal-title":"Neuron"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"43","DOI":"10.3233\/JAD-220720","article-title":"Alzheimer\u2019s Disease: A Systems View Provides a Unifying Explanation of Its Development","volume":"91","author":"Grobler","year":"2023","journal-title":"J. Alzheimers Dis."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"197","DOI":"10.7150\/thno.79535","article-title":"Role of primary aging hallmarks in Alzheimer\u2019s disease","volume":"13","author":"Zhao","year":"2023","journal-title":"Theranostics"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"952","DOI":"10.2174\/1567205013666160314150501","article-title":"Molecular Basis of Familial and Sporadic Alzheimer\u2019s Disease","volume":"13","author":"Dorszewska","year":"2016","journal-title":"Curr. Alzheimer Res."},{"key":"ref_10","first-page":"a006304","article-title":"Presenilins and gamma-secretase: Structure, function, and role in Alzheimer Disease","volume":"2","author":"Iwatsubo","year":"2012","journal-title":"Cold Spring Harb. Perspect. Med."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"693","DOI":"10.1016\/j.cell.2022.12.032","article-title":"Hallmarks of neurodegenerative diseases","volume":"186","author":"Wilson","year":"2023","journal-title":"Cell"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"3258","DOI":"10.1007\/s12035-020-01950-1","article-title":"Synaptic Loss, ER Stress and Neuro-Inflammation Emerge Late in the Lateral Temporal Cortex and Associate with Progressive Tau Pathology in Alzheimer\u2019s Disease","volume":"57","author":"Buchanan","year":"2020","journal-title":"Mol. Neurobiol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"111","DOI":"10.3892\/ijmm.2023.5314","article-title":"Inflammatory signaling pathways in the treatment of Alzheimer\u2019s disease with inhibitors, natural products and metabolites (Review)","volume":"52","author":"Zheng","year":"2023","journal-title":"Int. J. Mol. Med."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"94","DOI":"10.1038\/s41583-018-0113-1","article-title":"Beyond the neuron-cellular interactions early in Alzheimer disease pathogenesis","volume":"20","author":"Henstridge","year":"2019","journal-title":"Nat. Rev. Neurosci."},{"key":"ref_15","first-page":"575","article-title":"Inflammation as a central mechanism in Alzheimer\u2019s disease","volume":"4","author":"Kinney","year":"2018","journal-title":"Alzheimers Dement."},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Wang, M., Qin, L., and Tang, B. (2019). MicroRNAs in Alzheimer\u2019s Disease. Front. Genet., 10.","DOI":"10.3389\/fgene.2019.00153"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"506","DOI":"10.1038\/s41582-020-0369-8","article-title":"MicroRNAs as regulators of brain function and targets for treatment of epilepsy","volume":"16","author":"Brennan","year":"2020","journal-title":"Nat. Rev. Neurol."},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Di Benedetto, G., Burgaletto, C., Bellanca, C.M., Munafo, A., Bernardini, R., and Cantarella, G. (2022). Role of Microglia and Astrocytes in Alzheimer\u2019s Disease: From Neuroinflammation to Ca2+ Homeostasis Dysregulation. Cells, 11.","DOI":"10.3390\/cells11172728"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"10129","DOI":"10.1523\/JNEUROSCI.1202-06.2006","article-title":"Intraneuronal beta-amyloid aggregates, neurodegeneration, and neuron loss in transgenic mice with five familial Alzheimer\u2019s disease mutations: Potential factors in amyloid plaque formation","volume":"26","author":"Oakley","year":"2006","journal-title":"J. Neurosci."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1186\/s13024-017-0231-7","article-title":"Practical considerations for choosing a mouse model of Alzheimer\u2019s disease","volume":"12","author":"Jankowsky","year":"2017","journal-title":"Mol. Neurodegener."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"270","DOI":"10.1038\/s41597-021-01054-y","article-title":"Systematic phenotyping and characterization of the 5xFAD mouse model of Alzheimer\u2019s disease","volume":"8","author":"Forner","year":"2021","journal-title":"Sci. Data"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1631","DOI":"10.1002\/glia.23846","article-title":"Regulatory function of microRNAs in microglia","volume":"68","author":"Brites","year":"2020","journal-title":"Glia"},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Garcia, G., Pinto, S., Ferreira, S., Lopes, D., Serrador, M.J., Fernandes, A., Vaz, A.R., Mendon\u00e7a, A., Edenhofer, F., and Malm, T. (2022). Emerging Role of miR-21-5p in Neuron-Glia Dysregulation and Exosome Transfer Using Multiple Models of Alzheimer\u2019s Disease. Cells, 11.","DOI":"10.3390\/cells11213377"},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Rasheed, Z., Rasheed, N., Abdulmonem, W.A., and Khan, M.I. (2019). MicroRNA-125b-5p regulates IL-1beta induced inflammatory genes via targeting TRAF6-mediated MAPKs and NF-kappaB signaling in human osteoarthritic chondrocytes. Sci. Rep., 9.","DOI":"10.1038\/s41598-019-42601-3"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1270","DOI":"10.1038\/cr.2013.116","article-title":"MicroRNA-124 mediates the cholinergic anti-inflammatory action through inhibiting the production of pro-inflammatory cytokines","volume":"23","author":"Sun","year":"2013","journal-title":"Cell Res."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1016\/j.biochi.2018.05.015","article-title":"Secretome from SH-SY5Y APP(Swe) cells trigger time-dependent CHME3 microglia activation phenotypes, ultimately leading to miR-21 exosome shuttling","volume":"155","author":"Fernandes","year":"2018","journal-title":"Biochimie"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1133","DOI":"10.1016\/j.cell.2005.11.023","article-title":"Animal MicroRNAs confer robustness to gene expression and have a significant impact on 3\u2019UTR evolution","volume":"123","author":"Stark","year":"2005","journal-title":"Cell"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1161\/CIRCRESAHA.114.301633","article-title":"MicroRNA-124 controls the proliferative, migratory, and inflammatory phenotype of pulmonary vascular fibroblasts","volume":"114","author":"Wang","year":"2014","journal-title":"Circ. Res."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"548","DOI":"10.1016\/j.molmed.2011.06.009","article-title":"NeurimmiRs: microRNAs in the neuroimmune interface","volume":"17","author":"Soreq","year":"2011","journal-title":"Trends Mol. Med."},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Garcia, G., Pinto, S., Cunha, M., Fernandes, A., Koistinaho, J., and Brites, D. (2021). Neuronal Dynamics and miRNA Signaling Differ between SH-SY5Y APPSwe and PSEN1 Mutant iPSC-Derived AD Models upon Modulation with miR-124 Mimic and Inhibitor. Cells, 10.","DOI":"10.3390\/cells10092424"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"94","DOI":"10.1016\/j.toxlet.2011.11.032","article-title":"The miR-124 regulates the expression of BACE1\/beta-secretase correlated with cell death in Alzheimer\u2019s disease","volume":"209","author":"Fang","year":"2012","journal-title":"Toxicol. Lett."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"114065","DOI":"10.18632\/oncotarget.23119","article-title":"MiR-124 acts as a target for Alzheimer\u2019s disease by regulating BACE1","volume":"8","author":"An","year":"2017","journal-title":"Oncotarget"},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Liu, R., Du, J., Zhou, J., Zhong, B., Ba, L., Zhang, J., Liu, Y., and Liu, S. (2021). Elevated microRNA-21 Is a Brake of Inflammation Involved in the Development of Nasal Polyps. Front. Immunol., 12.","DOI":"10.3389\/fimmu.2021.530488"},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Amakiri, N., Kubosumi, A., Tran, J., and Reddy, P.H. (2019). Amyloid Beta and MicroRNAs in Alzheimer\u2019s Disease. Front. Neurosci., 13.","DOI":"10.3389\/fnins.2019.00430"},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Giuliani, A., Gaetani, S., Sorgentoni, G., Agarbati, S., Laggetta, M., Matacchione, G., Gobbi, M., Rossi, T., Galeazzi, R., and Piccinini, G. (2021). Circulating Inflamma-miRs as Potential Biomarkers of Cognitive Impairment in Patients Affected by Alzheimer\u2019s Disease. Front. Aging Neurosci., 13.","DOI":"10.3389\/fnagi.2021.647015"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"221","DOI":"10.1177\/1073858417721150","article-title":"MicroRNAs: Roles in Regulating Neuroinflammation","volume":"24","author":"Gaudet","year":"2018","journal-title":"Neuroscientist"},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"Wang, G., Huang, Y., Wang, L.L., Zhang, Y.F., Xu, J., Zhou, Y., Lourenco, G.F., Zhang, B., Wang, Y., and Ren, R.J. (2016). MicroRNA-146a suppresses ROCK1 allowing hyperphosphorylation of tau in Alzheimer\u2019s disease. Sci. Rep., 6.","DOI":"10.1038\/srep26697"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"102","DOI":"10.1016\/j.neurobiolaging.2019.06.005","article-title":"miR-146a and miR-181a are involved in the progression of mild cognitive impairment to Alzheimer\u2019s disease","volume":"82","author":"Ansari","year":"2019","journal-title":"Neurobiol. Aging"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"60","DOI":"10.1186\/s12974-023-02745-6","article-title":"Microglia specific deletion of miR-155 in Alzheimer\u2019s disease mouse models reduces amyloid-beta pathology but causes hyperexcitability and seizures","volume":"20","author":"Aloi","year":"2023","journal-title":"J. Neuroinflamm."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"6286","DOI":"10.1093\/hmg\/ddu348","article-title":"Early miR-155 upregulation contributes to neuroinflammation in Alzheimer\u2019s disease triple transgenic mouse model","volume":"23","author":"Guedes","year":"2014","journal-title":"Hum. Mol. Genet."},{"key":"ref_41","doi-asserted-by":"crossref","unstructured":"Zingale, V.D., Gugliandolo, A., and Mazzon, E. (2021). MiR-155: An Important Regulator of Neuroinflammation. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms23010090"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"267","DOI":"10.1016\/j.bbi.2019.02.011","article-title":"Microglia-mediated immunity partly contributes to the genetic association between Alzheimer\u2019s disease and hippocampal volume","volume":"79","author":"Lancaster","year":"2019","journal-title":"Brain Behav. Immun."},{"key":"ref_43","doi-asserted-by":"crossref","unstructured":"Zhang, Y., Liu, Z., Ji, B., Liu, L., Wu, S., Liu, X., Wang, S., and Wang, L. (2018). Metabolite Profile of Alzheimer\u2019s Disease in the Frontal Cortex as Analyzed by HRMAS (1)H NMR. Front. Aging Neurosci., 10.","DOI":"10.3389\/fnagi.2018.00424"},{"key":"ref_44","doi-asserted-by":"crossref","unstructured":"Liu, W., Li, J., Li, L., Zhang, Y., Yang, M., Liang, S., Li, L., Dai, Y., Chen, L., and Jia, W. (2022). Enhanced Medial Prefrontal Cortex and Hippocampal Activity Improves Memory Generalization in APP\/PS1 Mice: A Multimodal Animal MRI Study. Front. Cell. Neurosci., 16.","DOI":"10.3389\/fncel.2022.848967"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"5779","DOI":"10.1111\/jcmm.17593","article-title":"Identification of core genes in prefrontal cortex and hippocampus of Alzheimer\u2019s disease based on mRNA-miRNA network","volume":"26","author":"Huang","year":"2022","journal-title":"J. Cell. Mol. Med."},{"key":"ref_46","doi-asserted-by":"crossref","unstructured":"Hurst, C.D., Dunn, A.R., Dammer, E.B., Duong, D.M., Shapley, S.M., Seyfried, N.T., Kaczorowski, C.C., and Johnson, E.C.B. (2023). Genetic background influences the 5XFAD Alzheimer\u2019s disease mouse model brain proteome. Front. Aging Neurosci., 15.","DOI":"10.3389\/fnagi.2023.1239116"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1186\/1750-1326-9-33","article-title":"Temporal gene profiling of the 5XFAD transgenic mouse model highlights the importance of microglial activation in Alzheimer\u2019s disease","volume":"9","author":"Landel","year":"2014","journal-title":"Mol. Neurodegener."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"2220","DOI":"10.4103\/0366-6999.162507","article-title":"Reduction of Glucose Metabolism in Olfactory Bulb is an Earlier Alzheimer\u2019s Disease-related Biomarker in 5XFAD Mice","volume":"128","author":"Xiao","year":"2015","journal-title":"Chin. Med. J."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"488","DOI":"10.1111\/gbb.12133","article-title":"Abnormal vibrissa-related behavior and loss of barrel field inhibitory neurons in 5xFAD transgenics","volume":"13","author":"Flanigan","year":"2014","journal-title":"Genes. Brain Behav."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"312","DOI":"10.1038\/s41593-020-00783-4","article-title":"Reactive astrocyte nomenclature, definitions, and future directions","volume":"24","author":"Escartin","year":"2021","journal-title":"Nat. Neurosci."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"3458","DOI":"10.1016\/j.neuron.2022.10.020","article-title":"Microglia states and nomenclature: A field at its crossroads","volume":"110","author":"Paolicelli","year":"2022","journal-title":"Neuron"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"256","DOI":"10.1016\/j.stemcr.2020.06.001","article-title":"Human iPSC-Derived Hippocampal Spheroids: An Innovative Tool for Stratifying Alzheimer Disease Patient-Specific Cellular Phenotypes and Developing Therapies","volume":"15","author":"Pomeshchik","year":"2020","journal-title":"Stem Cell Rep."},{"key":"ref_53","doi-asserted-by":"crossref","unstructured":"Vaz, A.R., Vizinha, D., Morais, H., Colaco, A.R., Loch-Neckel, G., Barbosa, M., and Brites, D. (2021). Overexpression of miR-124 in Motor Neurons Plays a Key Role in ALS Pathological Processes. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22116128"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"56","DOI":"10.1186\/s40478-023-01554-5","article-title":"Myelin in Alzheimer\u2019s disease: Culprit or bystander?","volume":"11","author":"Maitre","year":"2023","journal-title":"Acta Neuropathol. Commun."},{"key":"ref_55","first-page":"4207","article-title":"Downregulated Glia Interplay and Increased miRNA-155 as Promising Markers to Track ALS at an Early Stage","volume":"55","author":"Cunha","year":"2018","journal-title":"Mol. Neurobiol."},{"key":"ref_56","doi-asserted-by":"crossref","unstructured":"Dainichi, T., Matsumoto, R., Mostafa, A., and Kabashima, K. (2019). Immune Control by TRAF6-Mediated Pathways of Epithelial Cells in the EIME (Epithelial Immune Microenvironment). Front. Immunol., 10.","DOI":"10.3389\/fimmu.2019.01107"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"96","DOI":"10.31083\/j.jin2204096","article-title":"Involvement of CXCL10 in Neuronal Damage under the Condition of Spinal Cord Injury and the Potential Therapeutic Effect of Nrg1","volume":"22","author":"Qiao","year":"2023","journal-title":"J. Integr. Neurosci."},{"key":"ref_58","doi-asserted-by":"crossref","unstructured":"Hu, C., Huang, Y., and Li, L. (2017). Drp1-Dependent Mitochondrial Fission Plays Critical Roles in Physiological and Pathological Progresses in Mammals. Int. J. Mol. Sci., 18.","DOI":"10.3390\/ijms18010144"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"4914","DOI":"10.1038\/s41467-019-12912-0","article-title":"Structural insights of human mitofusin-2 into mitochondrial fusion and CMT2A onset","volume":"10","author":"Li","year":"2019","journal-title":"Nat. Commun."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"421","DOI":"10.1093\/intimm\/dxr034","article-title":"A trio of microRNAs that control Toll-like receptor signalling","volume":"23","author":"Quinn","year":"2011","journal-title":"Int. Immunol."},{"key":"ref_61","doi-asserted-by":"crossref","unstructured":"Liang, Y., and Wang, L. (2021). Inflamma-MicroRNAs in Alzheimer\u2019s Disease: From Disease Pathogenesis to Therapeutic Potentials. Front. Cell. Neurosci., 15.","DOI":"10.3389\/fncel.2021.785433"},{"key":"ref_62","doi-asserted-by":"crossref","unstructured":"Liu, S., Fan, M., Zheng, Q., Hao, S., Yang, L., Xia, Q., Qi, C., and Ge, J. (2022). MicroRNAs in Alzheimer\u2019s disease: Potential diagnostic markers and therapeutic targets. Biomed. Pharmacother., 148.","DOI":"10.1016\/j.biopha.2022.112681"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"4117","DOI":"10.1016\/j.cell.2023.07.027","article-title":"Atlas of the aging mouse brain reveals white matter as vulnerable foci","volume":"186","author":"Hahn","year":"2023","journal-title":"Cell"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"3776","DOI":"10.1093\/brain\/awaa325","article-title":"Pathophysiological subtypes of Alzheimer\u2019s disease based on cerebrospinal fluid proteomics","volume":"143","author":"Tijms","year":"2020","journal-title":"Brain"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"1745","DOI":"10.14336\/AD.2022.0412","article-title":"Amyloid Cascade Hypothesis for the Treatment of Alzheimer\u2019s Disease: Progress and Challenges","volume":"13","author":"Wu","year":"2022","journal-title":"Aging Dis."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"2423","DOI":"10.1038\/s41380-022-01886-z","article-title":"Decoding the heterogeneity of Alzheimer\u2019s disease diagnosis and progression using multilayer networks","volume":"28","author":"Belloy","year":"2023","journal-title":"Mol. Psychiatry"},{"key":"ref_67","doi-asserted-by":"crossref","unstructured":"Abidin, S.Z., Mat Pauzi, N.A., Mansor, N.I., Mohd Isa, N.I., and Hamid, A.A. (2023). A new perspective on Alzheimer\u2019s disease: microRNAs and circular RNAs. Front. Genet., 14.","DOI":"10.3389\/fgene.2023.1231486"},{"key":"ref_68","doi-asserted-by":"crossref","unstructured":"Abuelezz, N.Z., Nasr, F.E., AbdulKader, M.A., Bassiouny, A.R., and Zaky, A. (2021). MicroRNAs as Potential Orchestrators of Alzheimer\u2019s Disease-Related Pathologies: Insights on Current Status and Future Possibilities. Front. Aging Neurosci., 13.","DOI":"10.3389\/fnagi.2021.743573"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"76","DOI":"10.1186\/s13024-021-00496-7","article-title":"The promise of microRNA-based therapies in Alzheimer\u2019s disease: Challenges and perspectives","volume":"16","author":"Walgrave","year":"2021","journal-title":"Mol. Neurodegener."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"2405","DOI":"10.1038\/s41380-022-01476-z","article-title":"Differential expression of MicroRNAs in Alzheimer\u2019s disease: A systematic review and meta-analysis","volume":"27","author":"Yoon","year":"2022","journal-title":"Mol. Psychiatry"},{"key":"ref_71","doi-asserted-by":"crossref","unstructured":"Yang, L., Qin, Y., and Jian, C. (2021). Screening for Core Genes Related to Pathogenesis of Alzheimer\u2019s Disease. Front. Cell Dev. Biol., 9.","DOI":"10.3389\/fcell.2021.668738"},{"key":"ref_72","doi-asserted-by":"crossref","unstructured":"Hill, M.A., and Gammie, S.C. (2022). Alzheimer\u2019s disease large-scale gene expression portrait identifies exercise as the top theoretical treatment. Sci. Rep., 12.","DOI":"10.1038\/s41598-022-22179-z"},{"key":"ref_73","doi-asserted-by":"crossref","unstructured":"Gentile, G., Morello, G., La Cognata, V., Guarnaccia, M., Conforti, F.L., and Cavallaro, S. (2022). Dysregulated miRNAs as Biomarkers and Therapeutical Targets in Neurodegenerative Diseases. J. Pers. Med., 12.","DOI":"10.3390\/jpm12050770"},{"key":"ref_74","doi-asserted-by":"crossref","unstructured":"Caldeira, C., Cunha, C., Vaz, A.R., Falcao, A.S., Barateiro, A., Seixas, E., Fernandes, A., and Brites, D. (2017). Key Aging-Associated Alterations in Primary Microglia Response to Beta-Amyloid Stimulation. Front. Aging Neurosci., 9.","DOI":"10.3389\/fnagi.2017.00277"},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"497","DOI":"10.1038\/s41593-018-0101-9","article-title":"Dysregulation of the epigenetic landscape of normal aging in Alzheimer\u2019s disease","volume":"21","author":"Nativio","year":"2018","journal-title":"Nat. Neurosci."},{"key":"ref_76","doi-asserted-by":"crossref","unstructured":"Wong-Guerra, M., Calfio, C., Maccioni, R.B., and Rojo, L.E. (2023). Revisiting the neuroinflammation hypothesis in Alzheimer\u2019s disease: A focus on the druggability of current targets. Front. Pharmacol., 14.","DOI":"10.3389\/fphar.2023.1161850"},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"267","DOI":"10.1038\/s41392-023-01486-5","article-title":"Role of neuroinflammation in neurodegeneration development","volume":"8","author":"Zhang","year":"2023","journal-title":"Signal Transduct. Target. Ther."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"157","DOI":"10.1038\/s41582-020-00435-y","article-title":"Neuroinflammation and microglial activation in Alzheimer disease: Where do we go from here?","volume":"17","author":"Leng","year":"2021","journal-title":"Nat. Rev. Neurol."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"114216","DOI":"10.1016\/j.celrep.2024.114216","article-title":"Microglia-astrocyte crosstalk in the amyloid plaque niche of an Alzheimer\u2019s disease mouse model, as revealed by spatial transcriptomics","volume":"43","author":"Mallach","year":"2024","journal-title":"Cell Rep."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"186","DOI":"10.1007\/s13311-021-01179-3","article-title":"Microglia in Alzheimer\u2019s Disease: A Key Player in the Transition between Homeostasis and Pathogenesis","volume":"19","author":"McFarland","year":"2022","journal-title":"Neurotherapeutics"},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"291","DOI":"10.1007\/s00439-019-02046-0","article-title":"MicroRNAs as modulators of longevity and the aging process","volume":"139","author":"Kinser","year":"2020","journal-title":"Hum. Genet."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"101374","DOI":"10.1016\/j.arr.2021.101374","article-title":"miR-21 and miR-146a: The microRNAs of inflammaging and age-related diseases","volume":"70","author":"Olivieri","year":"2021","journal-title":"Ageing Res. Rev."},{"key":"ref_83","doi-asserted-by":"crossref","unstructured":"Barbosa, M., Santos, M., de Sousa, N., Duarte-Silva, S., Vaz, A.R., Salgado, A.J., and Brites, D. (2022). Intrathecal Injection of the Secretome from ALS Motor Neurons Regulated for miR-124 Expression Prevents Disease Outcomes in SOD1-G93A Mice. Biomedicines, 10.","DOI":"10.3390\/biomedicines10092120"},{"key":"ref_84","doi-asserted-by":"crossref","unstructured":"Barbosa, M., Gomes, C., Sequeira, C., Goncalves-Ribeiro, J., Pina, C.C., Carvalho, L.A., Moreira, R., Vaz, S.H., Vaz, A.R., and Brites, D. (2021). Recovery of Depleted miR-146a in ALS Cortical Astrocytes Reverts Cell Aberrancies and Prevents Paracrine Pathogenicity on Microglia and Motor Neurons. Front. Cell Dev. Biol., 9.","DOI":"10.3389\/fcell.2021.634355"},{"key":"ref_85","doi-asserted-by":"crossref","unstructured":"Han, D., Dong, X., Zheng, D., and Nao, J. (2019). MiR-124 and the Underlying Therapeutic Promise of Neurodegenerative Disorders. Front. Pharmacol., 10.","DOI":"10.3389\/fphar.2019.01555"},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"1667","DOI":"10.15252\/embj.201387576","article-title":"MicroRNA-125b induces tau hyperphosphorylation and cognitive deficits in Alzheimer\u2019s disease","volume":"33","author":"Benito","year":"2014","journal-title":"EMBO J."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"473","DOI":"10.2174\/1567205016666190503145207","article-title":"Inhibition of microRNA-155 Alleviates Cognitive Impairment in Alzheimer\u2019s Disease and Involvement of Neuroinflammation","volume":"16","author":"Liu","year":"2019","journal-title":"Curr. Alzheimer Res."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"2564","DOI":"10.1038\/s12276-023-01123-9","article-title":"Spatiotemporal characterization of glial cell activation in an Alzheimer\u2019s disease model by spatially resolved transcriptomics","volume":"55","author":"Choi","year":"2023","journal-title":"Exp. Mol. Med."},{"key":"ref_89","first-page":"79","article-title":"Cystatin F as a key family 2 cystatin subunit and prognostic biomarker for early-stage pancreatic ductal adenocarcinoma","volume":"42","author":"Yang","year":"2019","journal-title":"Oncol. Rep."},{"key":"ref_90","doi-asserted-by":"crossref","unstructured":"Gharpure, M., Vyavahare, S., Ahluwalia, P., Gupta, S.K., Lee, T.J., Lohakare, J., Kolhe, R., Lei, Y., Deak, F., and Lu, X.Y. (2024). Alterations in Alzheimer\u2019s disease microglia transcriptome might be involved in bone pathophysiology. Neurobiol. Dis., 191.","DOI":"10.1016\/j.nbd.2024.106404"},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"234","DOI":"10.1186\/s12974-022-02581-0","article-title":"Comparative analysis of transcriptome remodeling in plaque-associated and plaque-distant microglia during amyloid-beta pathology progression in mice","volume":"19","author":"Meersseman","year":"2022","journal-title":"J. Neuroinflamm."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"1276","DOI":"10.1016\/j.cell.2017.05.018","article-title":"A Unique Microglia Type Associated with Restricting Development of Alzheimer\u2019s Disease","volume":"169","author":"Spinrad","year":"2017","journal-title":"Cell"},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1038\/s41577-022-00830-0","article-title":"Sex-specific role for microglial CST7 in Alzheimer\u2019s disease","volume":"23","author":"Baleviciute","year":"2023","journal-title":"Nat. Rev. Immunol."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"1215","DOI":"10.1002\/glia.24148","article-title":"The roles of microglia and astrocytes in phagocytosis and myelination: Insights from the cuprizone model of multiple sclerosis","volume":"70","author":"Sen","year":"2022","journal-title":"Glia"},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"608","DOI":"10.1016\/j.neuron.2020.08.012","article-title":"Astrocyte Crosstalk in CNS Inflammation","volume":"108","author":"Linnerbauer","year":"2020","journal-title":"Neuron"},{"key":"ref_96","doi-asserted-by":"crossref","unstructured":"Kim, K.Y., Shin, K.Y., and Chang, K.A. (2023). GFAP as a Potential Biomarker for Alzheimer\u2019s Disease: A Systematic Review and Meta-Analysis. Cells, 12.","DOI":"10.3390\/cells12091309"},{"key":"ref_97","doi-asserted-by":"crossref","unstructured":"Wang, X., Shi, Z., Qiu, Y., Sun, D., and Zhou, H. (2024). Peripheral GFAP and NfL as early biomarkers for dementia: Longitudinal insights from the UK Biobank. BMC Med., 22.","DOI":"10.1186\/s12916-024-03418-8"},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1056\/NEJMoa1211851","article-title":"TREM2 variants in Alzheimer\u2019s disease","volume":"368","author":"Guerreiro","year":"2013","journal-title":"N. Engl. J. Med."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"1438","DOI":"10.1002\/glia.20710","article-title":"TREM2 is upregulated in amyloid plaque-associated microglia in aged APP23 transgenic mice","volume":"56","author":"Frank","year":"2008","journal-title":"Glia"},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1038\/s41591-019-0695-9","article-title":"Human and mouse single-nucleus transcriptomics reveal TREM2-dependent and TREM2-independent cellular responses in Alzheimer\u2019s disease","volume":"26","author":"Zhou","year":"2020","journal-title":"Nat. Med."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"40","DOI":"10.1186\/s13024-022-00542-y","article-title":"TREM2 in the pathogenesis of AD: A lipid metabolism regulator and potential metabolic therapeutic target","volume":"17","author":"Li","year":"2022","journal-title":"Mol. Neurodegener."},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"66","DOI":"10.1186\/s13024-018-0298-9","article-title":"New insights into the role of TREM2 in Alzheimer\u2019s disease","volume":"13","author":"Gratuze","year":"2018","journal-title":"Mol. Neurodegener."},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"e20220654","DOI":"10.1084\/jem.20220654","article-title":"Chronic TREM2 activation exacerbates Abeta-associated tau seeding and spreading","volume":"220","author":"Jain","year":"2023","journal-title":"J. Exp. Med."},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"441","DOI":"10.1146\/annurev-immunol-051116-052358","article-title":"Microglia Function in the Central Nervous System During Health and Neurodegeneration","volume":"35","author":"Colonna","year":"2017","journal-title":"Annu. Rev. Immunol."},{"key":"ref_105","doi-asserted-by":"crossref","unstructured":"Bachiller, S., Jimenez-Ferrer, I., Paulus, A., Yang, Y., Swanberg, M., Deierborg, T., and Boza-Serrano, A. (2018). Microglia in Neurological Diseases: A Road Map to Brain-Disease Dependent-Inflammatory Response. Front. Cell. Neurosci., 12.","DOI":"10.3389\/fncel.2018.00488"},{"key":"ref_106","doi-asserted-by":"crossref","unstructured":"Bhattacharjee, S., Zhao, Y., Dua, P., Rogaev, E.I., and Lukiw, W.J. (2016). microRNA-34a-Mediated Down-Regulation of the Microglial-Enriched Triggering Receptor and Phagocytosis-Sensor TREM2 in Age-Related Macular Degeneration. PLoS ONE, 11.","DOI":"10.1371\/journal.pone.0150211"},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"2058","DOI":"10.1038\/s41467-024-46315-7","article-title":"BHLHE40\/41 regulate microglia and peripheral macrophage responses associated with Alzheimer\u2019s disease and other disorders of lipid-rich tissues","volume":"15","author":"Novikova","year":"2024","journal-title":"Nat. Commun."},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"22","DOI":"10.1186\/s40478-018-0515-3","article-title":"White matter changes in Alzheimer\u2019s disease: A focus on myelin and oligodendrocytes","volume":"6","author":"Nasrabady","year":"2018","journal-title":"Acta Neuropathol. Commun."},{"key":"ref_109","first-page":"3920","article-title":"MicroRNA-146a protects against intracerebral hemorrhage by inhibiting inflammation and oxidative stress","volume":"18","author":"Qu","year":"2019","journal-title":"Exp. Ther. Med."},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"E7140","DOI":"10.1073\/pnas.1706833114","article-title":"miR-146a-Traf6 regulatory axis controls autoimmunity and myelopoiesis, but is dispensable for hematopoietic stem cell homeostasis and tumor suppression","volume":"114","author":"Magilnick","year":"2017","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1186\/s12979-021-00258-5","article-title":"Knockdown of lncRNA BDNF-AS inhibited the progression of multiple myeloma by targeting the miR-125a\/b-5p-BCL2 axis","volume":"19","author":"Chu","year":"2022","journal-title":"Immun. Ageing"},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"273","DOI":"10.1016\/j.ibneur.2023.02.005","article-title":"Neuroprotective properties of anti-apoptotic BCL-2 proteins in 5xFAD mouse model of Alzheimer\u2019s disease","volume":"14","author":"Chernyuk","year":"2023","journal-title":"IBRO Neurosci. Rep."},{"key":"ref_113","doi-asserted-by":"crossref","unstructured":"Callens, M., Kraskovskaya, N., Derevtsova, K., Annaert, W., Bultynck, G., Bezprozvanny, I., and Vervliet, T. (2021). The role of Bcl-2 proteins in modulating neuronal Ca2+ signaling in health and in Alzheimer\u2019s disease. Biochim. Biophys. Acta Mol. Cell Res., 1868.","DOI":"10.1016\/j.bbamcr.2021.118997"},{"key":"ref_114","doi-asserted-by":"crossref","unstructured":"Oblak, A.L., Lin, P.B., Kotredes, K.P., Pandey, R.S., Garceau, D., Williams, H.M., Uyar, A., O\u2019Rourke, R., O\u2019Rourke, S., and Ingraham, C. (2021). Comprehensive Evaluation of the 5XFAD Mouse Model for Preclinical Testing Applications: A MODEL-AD Study. Front. Aging Neurosci., 13.","DOI":"10.3389\/fnagi.2021.713726"},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"fcab011","DOI":"10.1093\/braincomms\/fcab011","article-title":"Distinct microglial response against Alzheimer\u2019s amyloid and tau pathologies characterized by P2Y12 receptor","volume":"3","author":"Maeda","year":"2021","journal-title":"Brain Commun."},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"1121","DOI":"10.1111\/all.12643","article-title":"MicroRNA-155 modulates P2R signaling and Th2 priming of dendritic cells during allergic airway inflammation in mice","volume":"70","author":"Zech","year":"2015","journal-title":"Allergy"},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1186\/s12979-023-00383-3","article-title":"Toll-like receptor 4 (TLR4): New insight immune and aging","volume":"20","author":"Kim","year":"2023","journal-title":"Immun. Ageing"},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"100248","DOI":"10.1016\/j.bbih.2021.100248","article-title":"Immune receptor toll-like receptor 4 contributes to stress-induced affective responses in a sex-specific manner","volume":"14","author":"Quave","year":"2021","journal-title":"Brain Behav. Immun. Health"},{"key":"ref_119","doi-asserted-by":"crossref","unstructured":"Okun, E., Barak, B., Saada-Madar, R., Rothman, S.M., Griffioen, K.J., Roberts, N., Castro, K., Mughal, M.R., Pita, M.A., and Stranahan, A.M. (2012). Evidence for a developmental role for TLR4 in learning and memory. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0047522"},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"958","DOI":"10.1002\/hipo.23209","article-title":"Toll-like receptor 4 differentially regulates adult hippocampal neurogenesis in an age- and sex-dependent manner","volume":"30","author":"Connolly","year":"2020","journal-title":"Hippocampus"},{"key":"ref_121","doi-asserted-by":"crossref","first-page":"309","DOI":"10.3109\/08820139.2014.914533","article-title":"Fascin regulates TLR4\/PKC-mediated translational activation through miR-155 and miR-125b, which targets the 3\u2019 untranslated region of TNF-alpha mRNA","volume":"44","author":"Kim","year":"2015","journal-title":"Immunol. Investig."},{"key":"ref_122","doi-asserted-by":"crossref","first-page":"22","DOI":"10.1038\/s41419-017-0038-z","article-title":"MicroRNA-146a-5p attenuates irradiation-induced and LPS-induced hepatic stellate cell activation and hepatocyte apoptosis through inhibition of TLR4 pathway","volume":"9","author":"Chen","year":"2018","journal-title":"Cell Death Dis."},{"key":"ref_123","doi-asserted-by":"crossref","unstructured":"Liu, G.J., Zhang, Q.R., Gao, X., Wang, H., Tao, T., Gao, Y.Y., Zhou, Y., Chen, X.X., Li, W., and Hang, C.H. (2020). MiR-146a Ameliorates Hemoglobin-Induced Microglial Inflammatory Response via TLR4\/IRAK1\/TRAF6 Associated Pathways. Front. Neurosci., 14.","DOI":"10.3389\/fnins.2020.00311"},{"key":"ref_124","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1186\/1750-1326-8-2","article-title":"Neuron loss in the 5XFAD mouse model of Alzheimer\u2019s disease correlates with intraneuronal Abeta42 accumulation and Caspase-3 activation","volume":"8","author":"Eimer","year":"2013","journal-title":"Mol. Neurodegener."},{"key":"ref_125","first-page":"2373","article-title":"MicroRNA-125b regulates Alzheimer\u2019s disease through SphK1 regulation","volume":"18","author":"Jin","year":"2018","journal-title":"Mol. Med. Rep."},{"key":"ref_126","doi-asserted-by":"crossref","unstructured":"Fan, W., Liang, C., Ou, M., Zou, T., Sun, F., Zhou, H., and Cui, L. (2020). MicroRNA-146a Is a Wide-Reaching Neuroinflammatory Regulator and Potential Treatment Target in Neurological Diseases. Front. Mol. Neurosci., 13.","DOI":"10.3389\/fnmol.2020.00090"},{"key":"ref_127","doi-asserted-by":"crossref","first-page":"1511","DOI":"10.3233\/JAD-170094","article-title":"Overexpression of Kinesin Superfamily Motor Proteins in Alzheimer\u2019s Disease","volume":"60","author":"Hares","year":"2017","journal-title":"J. Alzheimers Dis."},{"key":"ref_128","doi-asserted-by":"crossref","unstructured":"Selvarasu, K., Singh, A.K., Iyaswamy, A., Gopalkrishnashetty Sreenivasmurthy, S., Krishnamoorthi, S., Bera, A.K., Huang, J.D., and Durairajan, S.S.K. (2022). Reduction of kinesin I heavy chain decreases tau hyperphosphorylation, aggregation, and memory impairment in Alzheimer\u2019s disease and tauopathy models. Front. Mol. Biosci., 9.","DOI":"10.3389\/fmolb.2022.1050768"},{"key":"ref_129","doi-asserted-by":"crossref","first-page":"1489","DOI":"10.1038\/s41593-023-01415-3","article-title":"Infiltrating CD8(+) T cells exacerbate Alzheimer\u2019s disease pathology in a 3D human neuroimmune axis model","volume":"26","author":"Jorfi","year":"2023","journal-title":"Nat. Neurosci."},{"key":"ref_130","doi-asserted-by":"crossref","first-page":"311","DOI":"10.5483\/BMBRep.2016.49.6.056","article-title":"MiR-146 and miR-125 in the regulation of innate immunity and inflammation","volume":"49","author":"Lee","year":"2016","journal-title":"BMB Rep."},{"key":"ref_131","doi-asserted-by":"crossref","first-page":"625","DOI":"10.3233\/JAD-220676","article-title":"Inflammation-Related microRNAs-146a and -155 Are Upregulated in Mild Cognitive Impairment Subjects Among Older Age Population in Montenegro","volume":"90","author":"Popovic","year":"2022","journal-title":"J. Alzheimers Dis."},{"key":"ref_132","doi-asserted-by":"crossref","first-page":"201129","DOI":"10.1016\/j.humgen.2022.201129","article-title":"The miR-146a-5p and miR-125b-5p levels as biomarkers for early prediction of Alzheimer\u2019s disease","volume":"34","author":"Yashooa","year":"2022","journal-title":"Hum. Gene"},{"key":"ref_133","doi-asserted-by":"crossref","first-page":"8060182","DOI":"10.1155\/2016\/8060182","article-title":"miR-155 Regulated Inflammation Response by the SOCS1-STAT3-PDCD4 Axis in Atherogenesis","volume":"2016","author":"Ye","year":"2016","journal-title":"Mediat. Inflamm."},{"key":"ref_134","doi-asserted-by":"crossref","first-page":"395","DOI":"10.1016\/j.biopsych.2017.07.023","article-title":"A Novel MicroRNA-124\/PTPN1 Signal Pathway Mediates Synaptic and Memory Deficits in Alzheimer\u2019s Disease","volume":"83","author":"Wang","year":"2018","journal-title":"Biol. Psychiatry"},{"key":"ref_135","doi-asserted-by":"crossref","first-page":"297","DOI":"10.1097\/WNR.0b013e3280148e8b","article-title":"Micro-RNA speciation in fetal, adult and Alzheimer\u2019s disease hippocampus","volume":"18","author":"Lukiw","year":"2007","journal-title":"Neuroreport"},{"key":"ref_136","doi-asserted-by":"crossref","first-page":"1955","DOI":"10.1111\/brv.12428","article-title":"Clustered miRNAs and their role in biological functions and diseases","volume":"93","author":"Kabekkodu","year":"2018","journal-title":"Biol. Rev. Camb. Philos. Soc."},{"key":"ref_137","doi-asserted-by":"crossref","first-page":"858","DOI":"10.1038\/s41586-024-07606-7","article-title":"Single-cell multiregion dissection of Alzheimer\u2019s disease","volume":"632","author":"Mathys","year":"2024","journal-title":"Nature"},{"key":"ref_138","doi-asserted-by":"crossref","first-page":"100078","DOI":"10.1016\/j.nbas.2023.100078","article-title":"The 5XFAD mouse model of Alzheimer\u2019s disease displays age-dependent deficits in habituation to a novel environment","volume":"3","author":"Smith","year":"2023","journal-title":"Aging Brain"},{"key":"ref_139","doi-asserted-by":"crossref","unstructured":"Poon, C.H., Wong, S.T.N., Roy, J., Wang, Y., Chan, H.W.H., Steinbusch, H., Blokland, A., Temel, Y., Aquili, L., and Lim, L.W. (2023). Sex Differences between Neuronal Loss and the Early Onset of Amyloid Deposits and Behavioral Consequences in 5xFAD Transgenic Mouse as a Model for Alzheimer\u2019s Disease. Cells, 12.","DOI":"10.3390\/cells12050780"},{"key":"ref_140","doi-asserted-by":"crossref","unstructured":"Zernov, N., Veselovsky, A.V., Poroikov, V.V., Melentieva, D., Bolshakova, A., and Popugaeva, E. (2022). New Positive TRPC6 Modulator Penetrates Blood-Brain Barrier, Eliminates Synaptic Deficiency and Restores Memory Deficit in 5xFAD Mice. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms232113552"},{"key":"ref_141","doi-asserted-by":"crossref","unstructured":"Zhang, M., Zhong, L., Han, X., Xiong, G., Xu, D., Zhang, S., Cheng, H., Chiu, K., and Xu, Y. (2021). Brain and Retinal Abnormalities in the 5xFAD Mouse Model of Alzheimer\u2019s Disease at Early Stages. Front. Neurosci., 15.","DOI":"10.3389\/fnins.2021.681831"},{"key":"ref_142","doi-asserted-by":"crossref","first-page":"1259","DOI":"10.3233\/JAD-180678","article-title":"5xFAD Mice Display Sex-Dependent Inflammatory Gene Induction During the Prodromal Stage of Alzheimer\u2019s Disease","volume":"70","author":"Manji","year":"2019","journal-title":"J. Alzheimers Dis."},{"key":"ref_143","doi-asserted-by":"crossref","first-page":"402","DOI":"10.1006\/meth.2001.1262","article-title":"Analysis of relative gene expression data using real-time quantitative PCR and the 2\u2212\u0394\u0394C(T) Method","volume":"25","author":"Livak","year":"2001","journal-title":"Methods"},{"key":"ref_144","doi-asserted-by":"crossref","first-page":"e133","DOI":"10.1093\/nar\/gku631","article-title":"The multiMiR R package and database: Integration of microRNA-target interactions along with their disease and drug associations","volume":"42","author":"Ru","year":"2014","journal-title":"Nucleic Acids Res."},{"key":"ref_145","first-page":"100141","article-title":"clusterProfiler 4.0: A universal enrichment tool for interpreting omics data","volume":"2","author":"Wu","year":"2021","journal-title":"Innovation"},{"key":"ref_146","doi-asserted-by":"crossref","unstructured":"Tang, D., Chen, M., Huang, X., Zhang, G., Zeng, L., Zhang, G., Wu, S., and Wang, Y. (2023). SRplot: A free online platform for data visualization and graphing. PLoS ONE, 18.","DOI":"10.1371\/journal.pone.0294236"}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/25\/17\/9475\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T15:46:09Z","timestamp":1760111169000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/25\/17\/9475"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,8,31]]},"references-count":146,"journal-issue":{"issue":"17","published-online":{"date-parts":[[2024,9]]}},"alternative-id":["ijms25179475"],"URL":"https:\/\/doi.org\/10.3390\/ijms25179475","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,8,31]]}}}