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Brains were harvested and processed for analysis of A\u03b2 plaques and Iba1 immunolabeling in cortex, hippocampus, and basolateral amygdala. Additional RNA sequencing data from separate age, strain, and sex matched mice were analyzed for differentially expressed genes (DEGs) and weighted gene co-expression networks.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>In both male and female mice, we observed increased functional connectivity in a dorsal striatal\/amygdala network due to A\u03b2. Increased functional connectivity within this network was matched by increases in A\u03b2PP gene expression, A\u03b2 and Iba1 immunolabeling, and an upregulated cluster of DEGs involved in the immune response. Conversely, the network measure representing node \u2018hubness\u2019, eigenvector centrality, was increased in prefrontal cortical brain regions, but only in female APP-PS1 mice. This female specific-effect of amyloid was associated with downregulation of a cluster of DEGs involved in cortical and striatal GABA transmission, anxiogenic responses, and motor activity, in female APP-PS1 mice, but not males.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Our results contribute to a growing literature linking between A\u03b2, immune activation and functional network connectivity. Furthermore, they reveal effects of A\u03b2 on gene expression patterns in female mice that may contribute to amyloidosis-induced dysregulation of non-cognitive circuitry.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1177\/13872877251378778","type":"journal-article","created":{"date-parts":[[2025,9,17]],"date-time":"2025-09-17T17:46:09Z","timestamp":1758131169000},"page":"893-913","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":0,"title":["Sex-dependent effect of amyloidosis on functional network \u2018hub\u2019 topology is associated with downregulated neuronal gene signatures in the APP\n                    <i>swe<\/i>\n                    \/PSEN1dE9 double transgenic mouse"],"prefix":"10.1177","volume":"108","author":[{"given":"Zachary D","family":"Simon","sequence":"first","affiliation":[{"name":"Department of Psychiatry, University of Florida, Gainesville, FL, USA"},{"name":"Department of Neuroscience, University of Florida, Gainesville, FL, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Karen N","family":"McFarland","sequence":"additional","affiliation":[{"name":"Department of Neurology, University of Florida, Gainesville, FL, USA"},{"name":"Department of Pharmacology and Chemical Biology; Center for Neurodegenerative Disease, Emory University, Atlanta, GA, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Todd E","family":"Golde","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Chemical Biology; Center for Neurodegenerative Disease, Emory University, Atlanta, GA, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6226-3776","authenticated-orcid":false,"given":"Paramita","family":"Chakrabarty","sequence":"additional","affiliation":[{"name":"Department of Neuroscience, University of Florida, Gainesville, FL, USA"},{"name":"Center for Translational Research in Neurodegenerative Disease, University of Florida, Gainesville, FL, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8981-4163","authenticated-orcid":false,"given":"Marcelo","family":"Febo","sequence":"additional","affiliation":[{"name":"Department of Psychiatry, University of Florida, Gainesville, FL, USA"},{"name":"Department of Neuroscience, University of Florida, Gainesville, FL, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"179","published-online":{"date-parts":[[2025,9,17]]},"reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1002\/alz.12638"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1001\/jamaneurol.2021.2161"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.3390\/jpm10020026"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.neurobiolaging.2010.03.025"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.neurobiolaging.2013.04.010"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroscience.2017.03.041"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1186\/s40478-018-0520-6"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1111\/ene.15043"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.3389\/neuro.05.028.2009"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2012.02.046"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.0702-23.2023"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.5062-08.2009"},{"key":"e_1_3_3_14_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0102995"},{"key":"e_1_3_3_15_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.nicl.2017.05.018"},{"key":"e_1_3_3_16_2","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0000000000004577"},{"key":"e_1_3_3_17_2","doi-asserted-by":"publisher","DOI":"10.1007\/s11682-021-00470-3"},{"key":"e_1_3_3_18_2","doi-asserted-by":"publisher","DOI":"10.1002\/hbm.22335"},{"key":"e_1_3_3_19_2","doi-asserted-by":"publisher","DOI":"10.1093\/braincomms\/fcab201"},{"key":"e_1_3_3_20_2","article-title":"Alteration of functional connectivity network in population of objectively-defined subtle cognitive decline","volume":"6","author":"Zhang X","year":"2024","unstructured":"Zhang X, Zeng Q, Wang Y, et al. 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