{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,19]],"date-time":"2026-06-19T03:34:43Z","timestamp":1781840083276,"version":"3.54.5"},"reference-count":66,"publisher":"MDPI AG","issue":"19","license":[{"start":{"date-parts":[[2023,10,5]],"date-time":"2023-10-05T00:00:00Z","timestamp":1696464000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100002283","name":"Alzheimer\u2019s Research UK","doi-asserted-by":"publisher","award":["ARUK-PPG2021B-012"],"award-info":[{"award-number":["ARUK-PPG2021B-012"]}],"id":[{"id":"10.13039\/501100002283","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Alzheimer\u2019s disease (AD) is the most common form of dementia, which disproportionately affects women. AD symptoms include progressive memory loss associated with amyloid-\u03b2 (A\u03b2) plaques and dismantled synaptic mechanisms. Perineuronal nets (PNNs) are important components of the extracellular matrix with a critical role in synaptic stabilisation and have been shown to be influenced by microglia, which enter an activated state during AD. This study aimed to investigate whether sex differences affected the density of PNNs alongside the labelling of microglia and A\u03b2 plaques density.We performed neurochemistry experiments using acute brain slices from both sexes of the APPNL-F\/NL-F mouse model of AD, aged-matched (2\u20135 and 12\u201316 months) to wild-type mice, combined with a weighted gene co-expression network analysis (WGCNA). The lateral entorhinal cortex (LEC) and hippocampal CA1, which are vulnerable during early AD pathology, were investigated and compared to the presubiculum (PRS), a region unscathed by AD pathology. The highest density of PNNs was found in the LEC and PRS regions of aged APPNL-F\/NL-F mice with a region-specific sex differences. Analysis of the CA1 region using multiplex-fluorescent images from aged APPNL-F\/NL-F mice showed regions of dense A\u03b2 plaques near clusters of CD68, indicative of activated microglia and PNNs. This was consistent with the results of WGCNA performed on normalised data on microglial cells isolated from age-matched, late-stage male and female wild-type and APP knock-in mice, which revealed one microglial module that showed differential expression associated with tissue, age, genotype, and sex, which showed enrichment for fc-receptor-mediated phagocytosis. Our data are consistent with the hypothesis that sex-related differences contribute to a disrupted interaction between PNNs and microglia in specific brain regions associated with AD pathogenesis.<\/jats:p>","DOI":"10.3390\/ijms241914917","type":"journal-article","created":{"date-parts":[[2023,10,5]],"date-time":"2023-10-05T09:14:22Z","timestamp":1696497262000},"page":"14917","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Age-Dependent Sex Differences in Perineuronal Nets in an APP Mouse Model of Alzheimer\u2019s Disease Are Brain Region-Specific"],"prefix":"10.3390","volume":"24","author":[{"given":"Rayane","family":"Rahmani","sequence":"first","affiliation":[{"name":"UCL School of Pharmacy, University College London, 29-39 Brunswick Square, London WC1N 1AX, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Naiomi","family":"Rambarack","sequence":"additional","affiliation":[{"name":"UCL School of Pharmacy, University College London, 29-39 Brunswick Square, London WC1N 1AX, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jaijeet","family":"Singh","sequence":"additional","affiliation":[{"name":"UCL School of Pharmacy, University College London, 29-39 Brunswick Square, London WC1N 1AX, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew","family":"Constanti","sequence":"additional","affiliation":[{"name":"UCL School of Pharmacy, University College London, 29-39 Brunswick Square, London WC1N 1AX, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Afia B.","family":"Ali","sequence":"additional","affiliation":[{"name":"UCL School of Pharmacy, University College London, 29-39 Brunswick Square, London WC1N 1AX, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,10,5]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"3611","DOI":"10.1111\/bph.14672","article-title":"The potential of memory enhancement through modulation of perineuronal nets","volume":"176","author":"Duncan","year":"2019","journal-title":"Br. J. Pharmacol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"e13129","DOI":"10.1111\/bpa.13129","article-title":"The fate of interneurons, GABA(A) receptor sub-types and perineuronal nets in Alzheimer\u2019s disease","volume":"33","author":"Ali","year":"2023","journal-title":"Brain Pathol."},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Soles, A., Selimovic, A., Sbrocco, K., Ghannoum, F., Hamel, K., Moncada, E.L., Gilliat, S., and Cvetanovic, M. (2023). Extracellular Matrix Regulation in Physiology and in Brain Disease. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms24087049"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"125","DOI":"10.1016\/j.semcdb.2018.09.011","article-title":"Perineuronal nets in brain physiology and disease","volume":"89","author":"Testa","year":"2019","journal-title":"Semin. Cell Dev. Biol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"458","DOI":"10.1016\/j.tins.2019.04.003","article-title":"Perineuronal Nets: Plasticity, Protection, and Therapeutic Potential","volume":"42","author":"Reichelt","year":"2019","journal-title":"Trends Neurosci."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"170","DOI":"10.1016\/0006-8993(89)90416-2","article-title":"Vicia villosa lectin-positive neurones in human cerebral cortex. Loss in Alzheimer-type dementia","volume":"498","author":"Kobayashi","year":"1989","journal-title":"Brain Res."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1435","DOI":"10.3233\/JAD-141200","article-title":"Increased levels of hyaluronic acid in cerebrospinal fluid in patients with vascular dementia","volume":"42","author":"Nagga","year":"2014","journal-title":"J. Alzheimer\u2019s Dis."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"896400","DOI":"10.3389\/fnint.2022.896400","article-title":"The \u201cLoss\u201d of Perineuronal Nets in Alzheimer\u2019s Disease: Missing or Hiding in Plain Sight?","volume":"16","author":"Scarlett","year":"2022","journal-title":"Front. Integr. Neurosci."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"103895","DOI":"10.1016\/j.isci.2022.103895","article-title":"Altered inhibitory function in hippocampal CA2 contributes in social memory deficits in Alzheimer\u2019s mouse model","volume":"25","author":"Rey","year":"2022","journal-title":"iScience"},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Reichelt, A.C. (2020). Is loss of perineuronal nets a critical pathological event in Alzheimer\u2019s disease?. EBioMedicine, 59.","DOI":"10.1016\/j.ebiom.2020.102946"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"5481","DOI":"10.1038\/s41380-021-01249-0","article-title":"The Amyloid-beta Pathway in Alzheimer\u2019s Disease","volume":"26","author":"Hampel","year":"2021","journal-title":"Mol. Psychiatry"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"124","DOI":"10.1016\/j.tins.2022.11.006","article-title":"Entorhinal cortex dysfunction in Alzheimer\u2019s disease","volume":"46","author":"Igarashi","year":"2023","journal-title":"Trends Neurosci."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"82","DOI":"10.1097\/00005072-199101000-00007","article-title":"Hippocampal lesions in dominantly inherited Alzheimer\u2019s disease","volume":"50","author":"Struble","year":"1991","journal-title":"J. Neuropathol. Exp. Neurol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"523","DOI":"10.1046\/j.1440-1819.2000.00747.x","article-title":"Neuronal loss and neurofibrillary degeneration in the hippocampal cortex in late-onset sporadic Alzheimer\u2019s disease","volume":"54","author":"Fukutani","year":"2000","journal-title":"Psychiatry Clin. Neurosci."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1016\/0304-3940(95)12083-G","article-title":"Neurons, intracellular and extracellular neurofibrillary tangles in subdivisions of the hippocampal cortex in normal ageing and Alzheimer\u2019s disease","volume":"200","author":"Fukutani","year":"1995","journal-title":"Neurosci. Lett."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"227","DOI":"10.1111\/j.1440-1819.1997.tb02588.x","article-title":"Neurons and extracellular neurofibrillary tangles in the hippocampal subdivisions in early-onset familial Alzheimer\u2019s disease: A case study","volume":"51","author":"Fukutani","year":"1997","journal-title":"Psychiatry Clin. Neurosci."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"459","DOI":"10.1083\/jcb.201709069","article-title":"Microglia in Alzheimer\u2019s disease","volume":"217","author":"Hansen","year":"2018","journal-title":"J. Cell Biol."},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Crapser, J.D., Spangenberg, E.E., Barahona, R.A., Arreola, M.A., Hohsfield, L.A., and Green, K.N. (2020). Microglia facilitate loss of perineuronal nets in the Alzheimer\u2019s disease brain. EBioMedicine, 58.","DOI":"10.1016\/j.ebiom.2020.102919"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"451","DOI":"10.1038\/s41583-019-0196-3","article-title":"The roles of perineuronal nets and the perinodal extracellular matrix in neuronal function","volume":"20","author":"Fawcett","year":"2019","journal-title":"Nat. Rev. Neurosci."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"e01265","DOI":"10.1002\/brb3.1265","article-title":"Age-dependent sexual dimorphism in hippocampal cornu ammonis-1 perineuronal net expression in rats","volume":"9","author":"Griffiths","year":"2019","journal-title":"Brain Behav."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1077","DOI":"10.3233\/JAD-180141","article-title":"Differences Between Women and Men in Incidence Rates of Dementia and Alzheimer\u2019s Disease","volume":"64","author":"Beam","year":"2018","journal-title":"J. Alzheimer\u2019s Dis."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"4907","DOI":"10.1007\/s00018-021-03830-w","article-title":"Alzheimer\u2019s pathogenic mechanisms and underlying sex difference","volume":"78","author":"Zhu","year":"2021","journal-title":"Cell Mol. Life Sci."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"385","DOI":"10.1016\/j.yfrne.2014.01.002","article-title":"Sex differences in cognitive impairment and Alzheimer\u2019s disease","volume":"35","author":"Li","year":"2014","journal-title":"Front. Neuroendocrinol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"2080","DOI":"10.4103\/1673-5374.241452","article-title":"Role of chondroitin sulfate proteoglycan signaling in regulating neuroinflammation following spinal cord injury","volume":"13","author":"Dyck","year":"2018","journal-title":"Neural Regen. Res."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"707165","DOI":"10.3389\/fnagi.2021.707165","article-title":"Application of Machine Learning and Weighted Gene Co-expression Network Algorithm to Explore the Hub Genes in the Aging Brain","volume":"13","author":"Chai","year":"2021","journal-title":"Front. Aging Neurosci."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"605961","DOI":"10.3389\/fnagi.2020.605961","article-title":"Co-expression Network Analysis Reveals Novel Genes Underlying Alzheimer\u2019s Disease Pathogenesis","volume":"12","author":"Hu","year":"2020","journal-title":"Front. Aging Neurosci."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"371","DOI":"10.1016\/0306-4522(94)90044-2","article-title":"Mapping of perineuronal nets in the rat brain stained by colloidal iron hydroxide histochemistry and lectin cytochemistry","volume":"58","author":"Seeger","year":"1994","journal-title":"Neuroscience"},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Lensjo, K.K., Christensen, A.C., Tennoe, S., Fyhn, M., and Hafting, T. (2017). Differential Expression and Cell-Type Specificity of Perineuronal Nets in Hippocampus, Medial Entorhinal Cortex, and Visual Cortex Examined in the Rat and Mouse. eNeuro, 4.","DOI":"10.1523\/ENEURO.0379-16.2017"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1016\/j.semcdb.2022.03.001","article-title":"Presubiculum principal cells are preserved from degeneration in knock-in App\/Tau mouse models of Alzheimer\u2019s disease","volume":"139","author":"Islam","year":"2023","journal-title":"Semin. Cell Dev. Biol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"838918","DOI":"10.3389\/fnmol.2022.838918","article-title":"Region-specific alterations of perineuronal net expression in postmortem autism brain tissue","volume":"15","author":"Brandenburg","year":"2022","journal-title":"Front. Mol. Neurosci."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1834","DOI":"10.1093\/cercor\/bhz016","article-title":"Aberrant Excitatory-Inhibitory Synaptic Mechanisms in Entorhinal Cortex Microcircuits During the Pathogenesis of Alzheimer\u2019s Disease","volume":"29","author":"Petrache","year":"2019","journal-title":"Cereb. Cortex"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"42370","DOI":"10.1038\/srep42370","article-title":"Entorhinal Cortex dysfunction can be rescued by inhibition of microglial RAGE in an Alzheimer\u2019s disease mouse model","volume":"7","author":"Criscuolo","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_33","first-page":"412","article-title":"Towards a circuit-level understanding of hippocampal CA1 dysfunction in Alzheimer\u2019s disease across anatomical axes","volume":"8","author":"Masurkar","year":"2018","journal-title":"J. Alzheimer\u2019s Dis. Park."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"195","DOI":"10.1016\/j.pharep.2014.09.004","article-title":"A review on Alzheimer\u2019s disease pathophysiology and its management: An update","volume":"67","author":"Kumar","year":"2015","journal-title":"Pharmacol. Rep."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"707466","DOI":"10.3389\/fnagi.2021.707466","article-title":"Role of the Extracellular Matrix in Alzheimer\u2019s Disease","volume":"13","author":"Sun","year":"2021","journal-title":"Front. Aging Neurosci."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"5479","DOI":"10.1038\/s41598-020-62163-z","article-title":"Reorganization of perineuronal nets in the medial Preoptic Area during the reproductive cycle in female rats","volume":"10","author":"Uriarte","year":"2020","journal-title":"Sci. Rep."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1016\/j.neuroscience.2011.11.035","article-title":"Estradiol acts via estrogen receptors alpha and beta on pathways important for synaptic plasticity in the mouse hippocampal formation","volume":"202","author":"Tsuda","year":"2012","journal-title":"Neuroscience"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"276","DOI":"10.1002\/cne.10393","article-title":"Estrogen receptor-beta colocalizes extensively with parvalbumin-labeled inhibitory neurons in the cortex, amygdala, basal forebrain, and hippocampal formation of intact and ovariectomized adult rats","volume":"452","author":"Tuszynski","year":"2002","journal-title":"J. Comp. Neurol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"4","DOI":"10.1037\/a0026708","article-title":"Estrogen effects on the brain: Actions beyond the hypothalamus via novel mechanisms","volume":"126","author":"Mcewen","year":"2012","journal-title":"Behav. Neurosci."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"16","DOI":"10.3389\/fphar.2013.00016","article-title":"Exploring the contribution of estrogen to amyloid-Beta regulation: A novel multifactorial computational modeling approach","volume":"4","author":"Anastasio","year":"2013","journal-title":"Front. Pharmacol."},{"key":"ref_41","doi-asserted-by":"crossref","unstructured":"Eskici, N.F., Erdem-Ozdamar, S., and Dayangac-Erden, D. (2018). The altered expression of perineuronal net elements during neural differentiation. Cell Mol. Biol. Lett., 23.","DOI":"10.1186\/s11658-018-0073-5"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"114098","DOI":"10.1016\/j.expneurol.2022.114098","article-title":"Regulation of perineuronal net components in the synaptic bouton vicinity on lumbar alpha-motoneurons in the rat after spinalization and locomotor training: New insights from spatio-temporal changes in gene, protein expression and Wfa labeling","volume":"354","author":"Grycz","year":"2022","journal-title":"Exp. Neurol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"4611","DOI":"10.1523\/JNEUROSCI.22-11-04611.2002","article-title":"Spinal cord injury elicits expression of keratan sulfate proteoglycans by macrophages, reactive microglia, and oligodendrocyte progenitors","volume":"22","author":"Jones","year":"2002","journal-title":"J. Neurosci."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"2472","DOI":"10.1038\/s41423-021-00751-3","article-title":"Microglia as hackers of the matrix: Sculpting synapses and the extracellular space","volume":"18","author":"Crapser","year":"2021","journal-title":"Cell Mol. Immunol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"95","DOI":"10.1016\/j.neuroscience.2005.07.031","article-title":"Construction of perineuronal net-like structure by cortical neurons in culture","volume":"136","author":"Miyata","year":"2005","journal-title":"Neuroscience"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"266","DOI":"10.1093\/brain\/awz363","article-title":"Microglial depletion prevents extracellular matrix changes and striatal volume reduction in a model of Huntington\u2019s disease","volume":"143","author":"Crapser","year":"2020","journal-title":"Brain"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"1274","DOI":"10.1523\/JNEUROSCI.2140-20.2020","article-title":"Microglia Elimination Increases Neural Circuit Connectivity and Activity in Adult Mouse Cortex","volume":"41","author":"Liu","year":"2021","journal-title":"J. Neurosci."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"e13182","DOI":"10.1111\/acel.13182","article-title":"Aging and sex: Impact on microglia phagocytosis","volume":"19","author":"Arevalo","year":"2020","journal-title":"Aging Cell"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"3536","DOI":"10.1093\/brain\/awac257","article-title":"Sex-specific effects of microglial activation on Alzheimer\u2019s disease proteinopathy in older adults","volume":"145","author":"Casaletto","year":"2022","journal-title":"Brain"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"247","DOI":"10.1186\/s12974-022-02604-w","article-title":"Alzheimer\u2019s disease-related transcriptional sex differences in myeloid cells","volume":"19","author":"Coales","year":"2022","journal-title":"J. Neuroinflamm."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"1293","DOI":"10.1016\/j.celrep.2019.03.099","article-title":"The Major Risk Factors for Alzheimer\u2019s Disease: Age, Sex, and Genes Modulate the Microglia Response to Abeta Plaques","volume":"27","author":"Wolfs","year":"2019","journal-title":"Cell Rep."},{"key":"ref_52","doi-asserted-by":"crossref","unstructured":"Guillot-Sestier, M.V., Araiz, A.R., Mela, V., Gaban, A.S., O\u2019Neill, E., Joshi, L., Chouchani, E.T., Mills, E.L., and Lynch, M.A. (2021). Microglial metabolism is a pivotal factor in sexual dimorphism in Alzheimer\u2019s disease. Commun. Biol., 4.","DOI":"10.1038\/s42003-021-02259-y"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"179","DOI":"10.1186\/1742-2094-9-179","article-title":"Extensive innate immune gene activation accompanies brain aging, increasing vulnerability to cognitive decline and neurodegeneration: A microarray study","volume":"9","author":"Cribbs","year":"2012","journal-title":"J. Neuroinflamm."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"235","DOI":"10.3389\/fnins.2014.00235","article-title":"New roles for Fc receptors in neurodegeneration-the impact on Immunotherapy for Alzheimer\u2019s Disease","volume":"8","author":"Fuller","year":"2014","journal-title":"Front. Neurosci."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"24","DOI":"10.1016\/j.neurobiolaging.2019.12.001","article-title":"Dysregulated Fc gamma receptor-mediated phagocytosis pathway in Alzheimer\u2019s disease: Network-based gene expression analysis","volume":"88","author":"Park","year":"2020","journal-title":"Neurobiol. Aging"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"1573","DOI":"10.1111\/j.1476-5381.2010.00873.x","article-title":"Guidelines for reporting experiments involving animals: The ARRIVE guidelines","volume":"160","author":"Mcgrath","year":"2010","journal-title":"Br. J. Pharmacol."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"661","DOI":"10.1038\/nn.3697","article-title":"Single App knock-in mouse models of Alzheimer\u2019s disease","volume":"17","author":"Saito","year":"2014","journal-title":"Nat. Neurosci."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"1272","DOI":"10.1093\/cercor\/bhz165","article-title":"Preserved Calretinin Interneurons in an App Model of Alzheimer\u2019s Disease Disrupt Hippocampal Inhibition via Upregulated P2Y1 Purinoreceptors","volume":"30","author":"Shi","year":"2020","journal-title":"Cereb. Cortex"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"120","DOI":"10.1016\/j.jneumeth.2012.05.019","article-title":"Introducing Amylo-Glo, a novel fluorescent amyloid specific histochemical tracer especially suited for multiple labeling and large scale quantification studies","volume":"209","author":"Schmued","year":"2012","journal-title":"J. Neurosci. Methods"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"674","DOI":"10.1038\/nature11729","article-title":"NLRP3 is activated in Alzheimer\u2019s disease and contributes to pathology in APP\/PS1 mice","volume":"493","author":"Heneka","year":"2013","journal-title":"Nature"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"211","DOI":"10.1007\/978-1-0716-0592-9_19","article-title":"Staining and Quantification of beta-Amyloid Pathology in Transgenic Mouse Models of Alzheimer\u2019s Disease","volume":"2144","author":"Christensen","year":"2020","journal-title":"Methods Mol. Biol."},{"key":"ref_62","doi-asserted-by":"crossref","unstructured":"Langfelder, P., and Horvath, S. (2008). Wgcna: An R package for weighted correlation network analysis. BMC Bioinform., 9.","DOI":"10.1186\/1471-2105-9-559"},{"key":"ref_63","doi-asserted-by":"crossref","unstructured":"Love, M.I., Huber, W., and Anders, S. (2014). Moderated estimation of fold change and dispersion for RNA-seq data with DESeq2. Genome Biol., 15.","DOI":"10.1186\/s13059-014-0550-8"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"D545","DOI":"10.1093\/nar\/gkaa970","article-title":"KEGG: Integrating viruses and cellular organisms","volume":"49","author":"Kanehisa","year":"2021","journal-title":"Nucleic Acids Res."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"1830","DOI":"10.1093\/bioinformatics\/btt285","article-title":"Pathview: An R\/Bioconductor package for pathway-based data integration and visualization","volume":"29","author":"Luo","year":"2013","journal-title":"Bioinformatics"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"2628","DOI":"10.1093\/bioinformatics\/btz931","article-title":"ShinyGO: A graphical gene-set enrichment tool for animals and plants","volume":"36","author":"Ge","year":"2020","journal-title":"Bioinformatics"}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/24\/19\/14917\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T21:01:33Z","timestamp":1760130093000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/24\/19\/14917"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,10,5]]},"references-count":66,"journal-issue":{"issue":"19","published-online":{"date-parts":[[2023,10]]}},"alternative-id":["ijms241914917"],"URL":"https:\/\/doi.org\/10.3390\/ijms241914917","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,10,5]]}}}