{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,14]],"date-time":"2026-09-14T22:43:50Z","timestamp":1789425830074,"version":"build-2803163510"},"reference-count":70,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2023,3,15]],"date-time":"2023-03-15T00:00:00Z","timestamp":1678838400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["RF1AG051514, RF1AG057247, RF1AG027297"],"award-info":[{"award-number":["RF1AG051514, RF1AG057247, RF1AG027297"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000957","name":"Alzheimer's Association","doi-asserted-by":"publisher","award":["AARFD-19-619290"],"award-info":[{"award-number":["AARFD-19-619290"]}],"id":[{"id":"10.13039\/100000957","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Cell. Neurosci."],"abstract":"<jats:p><jats:bold>Introduction:<\/jats:bold> Increasing evidence indicates that neurodegenerative diseases, including Alzheimer\u2019s disease (AD), are a product of gene-by-environment interplay. The immune system is a major contributor mediating these interactions. Signaling between peripheral immune cells and those within the microvasculature and meninges of the central nervous system (CNS), at the blood-brain barrier, and in the gut likely plays an important role in AD. The cytokine tumor necrosis factor (TNF) is elevated in AD patients, regulates brain and gut barrier permeability, and is produced by central and peripheral immune cells. Our group previously reported that soluble TNF (sTNF) modulates cytokine and chemokine cascades that regulate peripheral immune cell traffic to the brain in young 5xFAD female mice, and in separate studies that a diet high in fat and sugar (HFHS) dysregulates signaling pathways that trigger sTNF-dependent immune and metabolic responses that can result in metabolic syndrome, which is a risk factor for AD. We hypothesized that sTNF is a key mediator of peripheral immune cell contributions to gene-by-environment interactions to AD-like pathology, metabolic dysfunction, and diet-induced gut dysbiosis.<\/jats:p><jats:p><jats:bold>Methods:<\/jats:bold> Female 5xFAD mice were subjected to HFHS diet for 2 months and then given XPro1595 to inhibit sTNF for the last month or saline vehicle. We quantified immune cell profiles by multi-color flow cytometry on cells isolated from brain and blood; metabolic, immune, and inflammatory mRNA and protein marker biochemical and immunhistological analyses, gut microbiome, and electrophysiology in brain slices were also performed.<\/jats:p><jats:p><jats:bold>Results:<\/jats:bold> Here, we show that selective inhibition of sTNF signaling via the biologic XPro1595 modulates the effects of an HFHS diet in 5xFAD mice on peripheral and central immune profiles including CNS-associated CD8+ T cells, the composition of gut microbiota, and long-term potentiation deficits.<\/jats:p><jats:p><jats:bold>Discussion:<\/jats:bold> Obesogenic diet induces immune and neuronal dysfunction in 5xFAD mice and sTNF inhibition mitigates its effects. A clinical trial in subjects at risk for AD due to genetic predisposition and underlying inflammation associated with peripheral inflammatory co-morbidities will be needed to investigate the extent to which these findings translate to the clinic.<\/jats:p>","DOI":"10.3389\/fncel.2023.895017","type":"journal-article","created":{"date-parts":[[2023,3,15]],"date-time":"2023-03-15T11:39:40Z","timestamp":1678880380000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":19,"title":["Soluble TNF mediates amyloid-independent, diet-induced alterations to immune and neuronal functions in an Alzheimer\u2019s disease mouse model"],"prefix":"10.3389","volume":"17","author":[{"given":"Kathryn P.","family":"MacPherson","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lori N.","family":"Eidson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Madelyn C.","family":"Houser","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Blaine E.","family":"Weiss","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jenna L.","family":"Gollihue","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mary K.","family":"Herrick","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria Elizabeth","family":"de Sousa Rodrigues","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lindsey","family":"Sniffen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erica M.","family":"Weekman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adam M.","family":"Hamilton","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sean D.","family":"Kelly","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Danielle L.","family":"Oliver","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuan","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianjun","family":"Chang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Timothy R.","family":"Sampson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher M.","family":"Norris","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mal\u00fa G\u00e1mez","family":"Tansey","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2023,3,15]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"41","DOI":"10.1084\/jem.20180794","article-title":"Microbiome-microglia connections via the gut-brain axis","volume":"216","author":"Abdel-Haq","year":"2019","journal-title":"J. Exp. Med."},{"key":"B2","unstructured":"ggpubr: \u201cggplot2\u201d based publication ready plots. R package version 0.4.0\n            AlboukadelK.\n          2020"},{"key":"B3","doi-asserted-by":"publisher","first-page":"758518","DOI":"10.3389\/fnut.2021.758518","article-title":"Long-term overconsumption of fat and sugar causes a partially reversible pre-inflammatory bowel disease state","volume":"8","author":"Arnone","year":"2021","journal-title":"Front. Nutr."},{"key":"B4","doi-asserted-by":"publisher","first-page":"178","DOI":"10.1016\/j.brainresbull.2016.02.005","article-title":"Neuroprotective effects of metformin against A\u03b2-mediated inhibition of long-term potentiation in rats fed a high-fat diet","volume":"121","author":"Asadbegi","year":"2016","journal-title":"Brain Res. Bull."},{"key":"B5","doi-asserted-by":"publisher","first-page":"2282","DOI":"10.1126\/science.1067859","article-title":"Control of synaptic strength by glial TNF\u03b1","volume":"295","author":"Beattie","year":"2002","journal-title":"Science"},{"key":"B6","doi-asserted-by":"publisher","first-page":"265","DOI":"10.1016\/j.chom.2019.06.013","article-title":"Meta-analysis reveals reproducible gut microbiome alterations in response to a high-fat diet","volume":"26","author":"Bisanz","year":"2019","journal-title":"Cell Host Microbe"},{"key":"B7","doi-asserted-by":"publisher","first-page":"775","DOI":"10.3233\/JAD-160926","article-title":"Altered gut microbiome composition and tryptic activity of the 5xFAD Alzheimer\u2019s mouse model","volume":"56","author":"Brandscheid","year":"2017","journal-title":"J. Alzheimers Dis."},{"key":"B8","doi-asserted-by":"publisher","first-page":"622","DOI":"10.1038\/s41583-018-0057-5","article-title":"Microglial signatures and their role in health and disease","volume":"19","author":"Butovsky","year":"2018","journal-title":"Nat. Rev. Neurosci."},{"key":"B9","doi-asserted-by":"publisher","first-page":"581","DOI":"10.1038\/nmeth.3869","article-title":"DADA2: high-resolution sample inference from Illumina amplicon data","volume":"13","author":"Callahan","year":"2016","journal-title":"Nat. Methods"},{"key":"B10","doi-asserted-by":"publisher","first-page":"51","DOI":"10.1186\/s13024-018-0284-2","article-title":"Peripheral immune system in aging and Alzheimer\u2019s disease","volume":"13","author":"Cao","year":"2018","journal-title":"Mol. Neurodegener."},{"key":"B11","doi-asserted-by":"publisher","first-page":"1389","DOI":"10.1042\/CS20201394","article-title":"Cholesterol metabolism: a new molecular switch to control inflammation","volume":"135","author":"Cardoso","year":"2021","journal-title":"Clin. Sci. (Lond)"},{"key":"B12","doi-asserted-by":"publisher","first-page":"2535","DOI":"10.1097\/01.MIB.0000437042.59208.9f","article-title":"Tumor necrosis factor-neuropeptide Y cross talk regulates inflammation, epithelial barrier functions and colonic motility","volume":"19","author":"Chandrasekharan","year":"2013","journal-title":"Inflamm. Bowel Dis."},{"key":"B13","doi-asserted-by":"publisher","first-page":"844","DOI":"10.1016\/j.it.2021.08.010","article-title":"Trust your gut: an early life lesson for T cells","volume":"42","author":"Cowan","year":"2021","journal-title":"Trends Immunol."},{"key":"B14","first-page":"44","article-title":"Modulation of polymorphonuclear leukocyte locomotion by synthetic amphiphiles","volume":"24","author":"Dahlgren","year":"1980","journal-title":"Scand. J. Infect. Dis. Suppl."},{"key":"B15","doi-asserted-by":"publisher","first-page":"295","DOI":"10.1038\/ismej.2013.155","article-title":"High-fat diet alters gut microbiota physiology in mice","volume":"8","author":"Daniel","year":"2014","journal-title":"ISME J."},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1101\/221499","article-title":"Simple statistical identification and removal of contaminant sequences in marker-gene and metagenomics data","author":"Davis","year":"2017","journal-title":"bioRxiv"},{"key":"B17","doi-asserted-by":"publisher","first-page":"734158","DOI":"10.3389\/fnins.2021.734158","article-title":"Hippocampal function is impaired by a short-term high-fat diet in mice: increased blood-brain barrier permeability and neuroinflammation as triggering events","volume":"15","author":"de Paula","year":"2021","journal-title":"Front. Neurosci."},{"key":"B18","doi-asserted-by":"publisher","first-page":"158","DOI":"10.1016\/j.bbi.2016.08.021","article-title":"Chronic psychological stress and high-fat high-fructose diet disrupt metabolic and inflammatory gene networks in the brain, liver and gut and promote behavioral deficits in mice","volume":"59","author":"de Sousa Rodrigues","year":"2017","journal-title":"Brain Behav. Immun."},{"key":"B19","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1186\/s13195-019-0546-4","article-title":"Targeting soluble tumor necrosis factor as a potential intervention to lower risk for late-onset Alzheimer\u2019s disease associated with obesity, metabolic syndrome and type 2 diabetes","volume":"12","author":"De Sousa Rodrigues","year":"2019","journal-title":"Alzheimers Res. Ther."},{"key":"B21","doi-asserted-by":"publisher","first-page":"965","DOI":"10.1038\/nn.4030","article-title":"Host microbiota constantly control maturation and function of microglia in the CNS","volume":"18","author":"Erny","year":"2015","journal-title":"Nat. Neurosci."},{"key":"B22","doi-asserted-by":"publisher","first-page":"399","DOI":"10.1038\/s41586-019-1895-7","article-title":"Clonally expanded CD8 T cells patrol the cerebrospinal fluid in Alzheimer\u2019s disease","volume":"577","author":"Gate","year":"2020","journal-title":"Nature"},{"key":"B23","doi-asserted-by":"publisher","first-page":"656","DOI":"10.1126\/science.1178331","article-title":"Development of monocytes, macrophages and dendritic cells","volume":"327","author":"Geissmann","year":"2010","journal-title":"Science"},{"key":"B24","doi-asserted-by":"publisher","first-page":"198","DOI":"10.2174\/1567205012666150921103426","article-title":"The role of brain cholesterol and its oxidized products in Alzheimer\u2019s disease","volume":"13","author":"Giudetti","year":"2016","journal-title":"Curr. Alzheimer Res."},{"key":"B25","doi-asserted-by":"publisher","first-page":"328","DOI":"10.1038\/s41398-021-01443-2","article-title":"A diet high in sugar and fat influences neurotransmitter metabolism and then affects brain function by altering the gut microbiota","volume":"11","author":"Guo","year":"2021","journal-title":"Transl. Psychiatry"},{"key":"B26","doi-asserted-by":"publisher","first-page":"788","DOI":"10.1136\/jnnp.74.6.788","article-title":"Systemic infection, interleukin 1\u03b2 and cognitive decline in Alzheimer\u2019s disease","volume":"74","author":"Holmes","year":"2003","journal-title":"J. Neurol. Neurosurg. Psychiatry"},{"key":"B27","doi-asserted-by":"publisher","first-page":"768","DOI":"10.1212\/WNL.0b013e3181b6bb95","article-title":"Systemic inflammation and disease progression in Alzheimer disease","volume":"73","author":"Holmes","year":"2009","journal-title":"Neurology"},{"key":"B28","doi-asserted-by":"publisher","first-page":"75","DOI":"10.1038\/nature18848","article-title":"The microbiota in adaptive immune homeostasis and disease","volume":"535","author":"Honda","year":"2016","journal-title":"Nature"},{"key":"B29","doi-asserted-by":"publisher","first-page":"241","DOI":"10.1016\/j.immuni.2019.06.005","article-title":"The cytokine TNF promotes transcription factor SREBP activity and binding to inflammatory genes to activate macrophages and limit tissue repair","volume":"51","author":"Kusnadi","year":"2019","journal-title":"Immunity"},{"key":"B30","doi-asserted-by":"publisher","first-page":"28","DOI":"10.1186\/s40168-019-0637-2","article-title":"Sequence and cultivation study of Muribaculaceae reveals novel species, host preference and functional potential of this yet undescribed family","volume":"7","author":"Lagkouvardos","year":"2019","journal-title":"Microbiome"},{"key":"B31","doi-asserted-by":"publisher","first-page":"e003154","DOI":"10.1161\/JAHA.115.003154","article-title":"High-Fat-diet intake enhances cerebral amyloid angiopathy and cognitive impairment in a mouse model of Alzheimer\u2019s disease, independently of metabolic disorders","volume":"5","author":"Lin","year":"2018","journal-title":"J. Am. Heart Assoc."},{"key":"B32","doi-asserted-by":"publisher","first-page":"159","DOI":"10.1177\/1535370217743766","article-title":"Gut reactions: How the blood-brain barrier connects the microbiome and the brain","volume":"243","author":"Logsdon","year":"2018","journal-title":"Exp. Biol. Med. (Maywood)"},{"key":"B33","doi-asserted-by":"publisher","first-page":"2358","DOI":"10.3390\/ijms20092358","article-title":"Adipose tissue dysfunction as determinant of obesity-associated metabolic complications","volume":"20","author":"Longo","year":"2019","journal-title":"Int. J. Mol. Sci."},{"key":"B34","doi-asserted-by":"publisher","first-page":"550","DOI":"10.1186\/s13059-014-0550-8","article-title":"Moderated estimation of fold change and dispersion for RNA-seq data with DESeq2","volume":"15","author":"Love","year":"2014","journal-title":"Genome Biol."},{"key":"B35","doi-asserted-by":"publisher","first-page":"1353","DOI":"10.1093\/ije\/dyaa099","article-title":"Higher risk of dementia in English older individuals who are overweight or obese","volume":"49","author":"Ma","year":"2020","journal-title":"Int. J. Epidemiol."},{"key":"B36","doi-asserted-by":"publisher","first-page":"81","DOI":"10.1016\/j.nbd.2017.02.010","article-title":"Peripheral administration of the soluble TNF inhibitor XPro1595 modifies brain immune cell profiles, decreases beta-amyloid plaque load and rescues impaired long-term potentiation in 5xFAD mice","volume":"102","author":"MacPherson","year":"2017","journal-title":"Neurobiol. Dis."},{"key":"B37","doi-asserted-by":"publisher","first-page":"1039","DOI":"10.1007\/s00109-018-1674-1","article-title":"Tumor necrosis factor (TNF) modulates synaptic plasticity in a concentration-dependent manner through intracellular calcium stores","volume":"96","author":"Maggio","year":"2018","journal-title":"J. Mol. Med. (Berl)"},{"key":"B373","doi-asserted-by":"publisher","first-page":"e2330","DOI":"10.3791\/2330","article-title":"Preparation of acute hippocampal slices from rats and transgenic mice for the study of synaptic alterations during aging and amyloid pathology","volume":"49","author":"Mathis","year":"2011","journal-title":"J. Vis. Exp."},{"key":"B38","doi-asserted-by":"publisher","first-page":"e61217","DOI":"10.1371\/journal.pone.0061217","article-title":"phyloseq: an R package for reproducible interactive analysis and graphics of microbiome census data","volume":"8","author":"McMurdie","year":"2013","journal-title":"PLoS One"},{"key":"B39","doi-asserted-by":"publisher","first-page":"49","DOI":"10.1159\/000486200","article-title":"Extravascular CD3+ T cells in brains of Alzheimer disease patients correlate with tau but not with amyloid pathology: an immunohistochemical study","volume":"18","author":"Merlini","year":"2018","journal-title":"Neurodegener. Dis."},{"key":"B40","doi-asserted-by":"publisher","first-page":"230","DOI":"10.1007\/s003840050095","article-title":"Small bowel length in inflammatory bowel disease","volume":"12","author":"Nordgren","year":"1997","journal-title":"Int. J. Colorectal Dis."},{"key":"B41","doi-asserted-by":"publisher","first-page":"10129","DOI":"10.1523\/JNEUROSCI.1202-06.2006","article-title":"Intraneuronal \u03b2-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":"B42","doi-asserted-by":"publisher","first-page":"8281","DOI":"10.3390\/ijerph120708281","article-title":"Evaluating the association between diabetes, cognitive decline and dementia","volume":"12","author":"Ojo","year":"2015","journal-title":"Int. J. Environ. Res. Public Health"},{"key":"B43","unstructured":"vegan: community ecology package. R package version 2.5-7\n            OksanenJ.\n            BlanchetF. G.\n            SimpsonG. L.\n            KindtR.\n            LegendreP.\n            McGlinnP. R.\n          2020"},{"key":"B44","doi-asserted-by":"publisher","first-page":"200","DOI":"10.3389\/fimmu.2020.00200","article-title":"Murine gut microbiome association with APOE alleles","volume":"11","author":"Parikh","year":"2020","journal-title":"Front. Immunol."},{"key":"B45","doi-asserted-by":"publisher","first-page":"1521","DOI":"10.1016\/j.bbadis.2016.05.007","article-title":"Calcineurin proteolysis in astrocytes: implications for impaired synaptic function","volume":"1862","author":"Pleiss","year":"2016","journal-title":"Biochim. Biophys. Acta"},{"key":"B46","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1007\/s11011-016-9917-8","article-title":"Diet, gut microbiota and cognition","volume":"32","author":"Proctor","year":"2017","journal-title":"Metab. Brain Dis."},{"key":"B47","unstructured":"R: a language and environment for statistical computingVienna, Austria: R Foundation for Statistical Computing.2020"},{"key":"B48","doi-asserted-by":"publisher","first-page":"236","DOI":"10.1016\/j.neuroscience.2014.11.014","article-title":"Calorie restriction increases lipopolysaccharide-induced neuropeptide Y immunolabeling and reduces microglial cell area in the arcuate hypothalamic nucleus","volume":"285","author":"Radler","year":"2015","journal-title":"Neuroscience"},{"key":"B49","doi-asserted-by":"publisher","first-page":"462","DOI":"10.1007\/s11481-009-9166-2","article-title":"CNS infiltration of peripheral immune cells: D-day for neurodegenerative disease?","volume":"4","author":"Rezai-Zadeh","year":"2009","journal-title":"J. Neuroimmune Pharmacol."},{"key":"B50","doi-asserted-by":"publisher","first-page":"12","DOI":"10.1007\/s11906-018-0812-z","article-title":"The global epidemic of the metabolic syndrome","volume":"20","author":"Saklayen","year":"2018","journal-title":"Curr. Hypertens Rep."},{"key":"B51","doi-asserted-by":"publisher","first-page":"82","DOI":"10.1016\/j.nbd.2018.02.001","article-title":"High fat diet treatment impairs hippocampal long-term potentiation without alterations of the core neuropathological features of Alzheimer disease","volume":"113","author":"Salas","year":"2018","journal-title":"Neurobiol. Dis."},{"key":"B52","doi-asserted-by":"publisher","first-page":"638","DOI":"10.1016\/j.tins.2012.06.001","article-title":"TNF\u03b1 in synaptic function: switching gears","volume":"35","author":"Santello","year":"2012","journal-title":"Trends Neurosci."},{"key":"B53","doi-asserted-by":"publisher","first-page":"1348","DOI":"10.3390\/nu12051348","article-title":"High intake of sugar and the balance between pro- and anti-inflammatory gut bacteria","volume":"12","author":"Satokari","year":"2020","journal-title":"Nutrients"},{"key":"B54","doi-asserted-by":"publisher","first-page":"3188","DOI":"10.3390\/cells10113188","article-title":"Fecal microbiome changes and specific anti-bacterial response in patients with IBD during anti-TNF therapy","volume":"10","author":"Schierova","year":"2021","journal-title":"Cells"},{"key":"B55","doi-asserted-by":"publisher","first-page":"e22107","DOI":"10.1096\/fj.202101297R","article-title":"Impact of metabolic disorders on the structural, functional and immunological integrity of the blood-brain barrier: therapeutic avenues","volume":"36","author":"Sheikh","year":"2022","journal-title":"FASEB J."},{"key":"B56","doi-asserted-by":"publisher","first-page":"779","DOI":"10.3390\/cells10040779","article-title":"Alterations in the gut-microbial-inflammasome-brain axis in a mouse model of Alzheimer\u2019s disease","volume":"10","author":"Shukla","year":"2021","journal-title":"Cells"},{"key":"B57","doi-asserted-by":"publisher","first-page":"6132","DOI":"10.1523\/JNEUROSCI.0877-17.2017","article-title":"Calcineurin\/NFAT signaling in activated astrocytes drives network hyperexcitability in A\u03b2-bearing mice","volume":"37","author":"Sompol","year":"2017","journal-title":"J. Neurosci."},{"key":"B58","doi-asserted-by":"publisher","first-page":"1895","DOI":"10.1126\/science.1081297","article-title":"Inactivation of TNF signaling by rationally designed dominant-negative TNF variants","volume":"301","author":"Steed","year":"2003","journal-title":"Science"},{"key":"B59","doi-asserted-by":"publisher","first-page":"657","DOI":"10.1038\/s41577-022-00684-6","article-title":"Inflammation and immune dysfunction in Parkinson disease","volume":"22","author":"Tansey","year":"2022","journal-title":"Nat. Rev. Immunol."},{"key":"B60","doi-asserted-by":"publisher","first-page":"83","DOI":"10.1016\/s0165-5728(01)00496-9","article-title":"Occurrence of T cells in the brain of Alzheimer\u2019s disease and other neurological diseases","volume":"124","author":"Togo","year":"2002","journal-title":"J. Neuroimmunol."},{"key":"B61","doi-asserted-by":"publisher","first-page":"67","DOI":"10.1016\/j.bbi.2020.05.070","article-title":"CD8 + T-cells infiltrate Alzheimer\u2019s disease brains and regulate neuronal- and synapse-related gene expression in APP-PS1 transgenic mice","volume":"89","author":"Unger","year":"2020","journal-title":"Brain Behav. Immun."},{"key":"B62","doi-asserted-by":"publisher","first-page":"74","DOI":"10.1016\/j.bbi.2019.07.019","article-title":"Monocyte mobilisation, microbiota & mental illness","volume":"81","author":"van de Wouw","year":"2019","journal-title":"Brain Behav. Immun."},{"key":"B63","doi-asserted-by":"publisher","first-page":"15","DOI":"10.1186\/s13024-019-0315-7","article-title":"Differential effects of diet- and genetically-induced brain insulin resistance on amyloid pathology in a mouse model of Alzheimer\u2019s disease","volume":"14","author":"Wakabayashi","year":"2019","journal-title":"Mol. Neurodegener."},{"key":"B64","doi-asserted-by":"publisher","first-page":"7332","DOI":"10.3390\/nu7095341","article-title":"Shared neuropathological characteristics of obesity, type 2 diabetes and Alzheimer\u2019s disease: impacts on cognitive decline","volume":"7","author":"Walker","year":"2015","journal-title":"Nutrients"},{"key":"B65","doi-asserted-by":"publisher","first-page":"116","DOI":"10.1515\/tnsci-2020-0098","article-title":"Plasma cholesterol in Alzheimer\u2019s disease and frontotemporal dementia","volume":"11","author":"Wang","year":"2020","journal-title":"Transl. Neurosci."},{"key":"B66","doi-asserted-by":"publisher","first-page":"1686","DOI":"10.21105\/joss.01686","article-title":"Welcome to the tidyverse","volume":"4","author":"Wickham","year":"2019","journal-title":"J. Open Source Softw."},{"key":"B777","doi-asserted-by":"publisher","first-page":"1537","DOI":"10.1523\/JNEUROSCI.5066-07.2008","article-title":"Progression of amyloid pathology to Alzheimer\u2019s disease pathology in an amyloid precursor protein transgenic mouse model by removal of nitric oxide synthase 2","volume":"28","author":"Wilcock","year":"2008","journal-title":"J. Neurosci."},{"key":"B700","doi-asserted-by":"publisher","first-page":"11","DOI":"10.1186\/1742-2094-11-57","article-title":"Comparison of microglia and infiltrating CD11c+ cells as antigen presenting cells for T cell proliferation and cytokine response","volume":"25","author":"Wlodarczyk","year":"2014","journal-title":"J. Neuroinflammation"},{"key":"B67","doi-asserted-by":"publisher","first-page":"2060","DOI":"10.1161\/ATVBAHA.112.252759","article-title":"Impact of metabolic syndrome on cognition and brain: a selected review of the literature","volume":"32","author":"Yates","year":"2012","journal-title":"Arterioscler. Thromb. Vasc. Biol."},{"key":"B68","doi-asserted-by":"publisher","first-page":"492","DOI":"10.1038\/s41422-020-0332-7","article-title":"Interaction between microbiota and immunity in health and disease","volume":"30","author":"Zheng","year":"2020","journal-title":"Cell Res."}],"container-title":["Frontiers in Cellular Neuroscience"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fncel.2023.895017\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,3,15]],"date-time":"2023-03-15T11:39:46Z","timestamp":1678880386000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fncel.2023.895017\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,3,15]]},"references-count":70,"alternative-id":["10.3389\/fncel.2023.895017"],"URL":"https:\/\/doi.org\/10.3389\/fncel.2023.895017","relation":{},"ISSN":["1662-5102"],"issn-type":[{"value":"1662-5102","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,3,15]]},"article-number":"895017"}}