{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T03:15:26Z","timestamp":1788232526153,"version":"build-2803163510"},"reference-count":78,"publisher":"Oxford University Press (OUP)","issue":"1","license":[{"start":{"date-parts":[[2024,12,14]],"date-time":"2024-12-14T00:00:00Z","timestamp":1734134400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Race Against Dementia Fellowship, Alzheimer\u2019s Research UK","award":["ARUK-RADF2019A-007"],"award-info":[{"award-number":["ARUK-RADF2019A-007"]}]},{"name":"Alzheimer\u2019s Research UK Senior Fellowship","award":["ARUK-SRF2023A-001"],"award-info":[{"award-number":["ARUK-SRF2023A-001"]}]},{"name":"MRC Senior Clinical Fellowship","award":["MR\/S006591\/1"],"award-info":[{"award-number":["MR\/S006591\/1"]}]},{"name":"Lister Institute Research Prize Fellowship"},{"name":"UKRI-MRC","award":["MR\/Y014847\/1"],"award-info":[{"award-number":["MR\/Y014847\/1"]}]},{"DOI":"10.13039\/501100017510","name":"UK Dementia Research Institute","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100017510","id-type":"DOI","asserted-by":"publisher"}]},{"name":"DRI Ltd"},{"name":"UK Medical Research Council and the Royal Society"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2024,12,24]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Extracellular beta-amyloid aggregation and inflammation are in a complex and not fully understood interplay during hyperphosphorylated tau aggregation and pathogenesis of Alzheimer\u2019s disease. Our group has previously shown that an immune challenge with tumour necrosis factor alpha can alter extracellular beta-sheet containing aggregates in human-induced pluripotent stem cell-derived cortical neurons carrying familial Alzheimer\u2019s disease-related presenilin 1 mutations. Here, using single-molecule detection and super-resolution imaging techniques, we quantified and characterized the intra- and extracellular beta-amyloid and AT8-positive tau aggregates. Our results indicate a pre-existing Alzheimer\u2019s disease-like pathology caused by the presenilin 1 mutation, with increased beta-amyloid aggregates in both the cell lysate and conditioned media compared to isogenic controls and also increased intracellular tau aggregates. The main effect of tumour necrosis factor alpha treatment on presenilin 1 neurons was the formation of larger intracellular beta-amyloid aggregates. In contrast, isogenic controls showed more significant changes with tumour necrosis factor alpha treatment with an increase in beta-amyloid aggregates in the media but not intracellularly and an increase in tau aggregates in both the media and cell lysate, suggesting a chronic inflammation-driven mechanism for the development of sporadic Alzheimer\u2019s disease. Remarkably, we also found significant morphological differences between intra- and extracellular beta-amyloid and tau aggregates in human-induced pluripotent stem cell-derived cortical neurons, suggesting these neurons can only clear aggregates when small, and that larger aggregates stay inside the neurons. While majority of the beta-amyloid aggregates were cleared into the media, a greater portion of the tau aggregates remained intracellular. This size-dependent aggregate clearance was also shown to be conserved in vivo, using soaked and homogenized mouse and human post-mortem Alzheimer\u2019s disease brain samples. As such, our results are proposing a previously unknown, size-dependent aggregate clearance mechanism, which can possibly explain the intracellular aggregation of tau and extracellular aggregation of beta-amyloid.<\/jats:p>","DOI":"10.1093\/braincomms\/fcae454","type":"journal-article","created":{"date-parts":[[2024,12,14]],"date-time":"2024-12-14T22:00:39Z","timestamp":1734213639000},"source":"Crossref","is-referenced-by-count":16,"title":["Clearance of beta-amyloid and tau aggregates is size dependent and altered by an inflammatory challenge"],"prefix":"10.1093","volume":"7","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0060-5806","authenticated-orcid":false,"given":"Emre","family":"Fertan","sequence":"first","affiliation":[{"name":"Yusuf Hamied Department of Chemistry, University of Cambridge , Cambridge CB2 1EW ,","place":["UK"]},{"name":"UK Dementia Research Institute, University of Cambridge , Cambridge CB2 0XY ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0056-7587","authenticated-orcid":false,"given":"Christy","family":"Hung","sequence":"additional","affiliation":[{"name":"The Francis Crick Institute, University College London , London NW1 1AT ,","place":["UK"]},{"name":"Department of Neuroscience, City University of Hong Kong , Kowloon 999007 ,","place":["Hong Kong SAR"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9882-8441","authenticated-orcid":false,"given":"John S H","family":"Danial","sequence":"additional","affiliation":[{"name":"Yusuf Hamied Department of Chemistry, University of Cambridge , Cambridge CB2 1EW ,","place":["UK"]},{"name":"UK Dementia Research Institute, University of Cambridge , Cambridge CB2 0XY ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeff Y L","family":"Lam","sequence":"additional","affiliation":[{"name":"Yusuf Hamied Department of Chemistry, University of Cambridge , Cambridge CB2 1EW ,","place":["UK"]},{"name":"UK Dementia Research Institute, University of Cambridge , Cambridge CB2 0XY ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pranav","family":"Preman","sequence":"additional","affiliation":[{"name":"VIB-KU Leuven Center for Brain & Disease Research , Herestraat 49, 0N5 box 602, 3000 Leuven ,","place":["Belgium"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giulia","family":"Albertini","sequence":"additional","affiliation":[{"name":"VIB-KU Leuven Center for Brain & Disease Research , Herestraat 49, 0N5 box 602, 3000 Leuven ,","place":["Belgium"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elizabeth A","family":"English","sequence":"additional","affiliation":[{"name":"Yusuf Hamied Department of Chemistry, University of Cambridge , Cambridge CB2 1EW ,","place":["UK"]},{"name":"UK Dementia Research Institute, University of Cambridge , Cambridge CB2 0XY ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-8443-4469","authenticated-orcid":false,"given":"Dorothea","family":"B\u00f6ken","sequence":"additional","affiliation":[{"name":"Yusuf Hamied Department of Chemistry, University of Cambridge , Cambridge CB2 1EW ,","place":["UK"]},{"name":"UK Dementia Research Institute, University of Cambridge , Cambridge CB2 0XY ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Frederick J","family":"Livesey","sequence":"additional","affiliation":[{"name":"Zayed Centre for Research into Rare Disease in Children, University College London, Great Ormond Street Institute of Child Health , London WC1N 1DZ ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bart","family":"De Strooper","sequence":"additional","affiliation":[{"name":"VIB-KU Leuven Center for Brain & Disease Research , Herestraat 49, 0N5 box 602, 3000 Leuven ,","place":["Belgium"]},{"name":"UK Dementia Research Institute, University College London , London WC1E 6BT ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3825-7675","authenticated-orcid":false,"given":"Rickie","family":"Patani","sequence":"additional","affiliation":[{"name":"The Francis Crick Institute, University College London , London NW1 1AT ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Klenerman","sequence":"additional","affiliation":[{"name":"Yusuf Hamied Department of Chemistry, University of Cambridge , Cambridge CB2 1EW ,","place":["UK"]},{"name":"UK Dementia Research Institute, University of Cambridge , Cambridge CB2 0XY ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2024,12,14]]},"reference":[{"issue":"1","key":"2025010217184737400_fcae454-B1","doi-asserted-by":"crossref","first-page":"a006189","DOI":"10.1101\/cshperspect.a006189","article-title":"Neuropathological alterations in Alzheimer disease","volume":"1","author":"Serrano-Pozo","year":"2011","journal-title":"Cold Spring Harb Perspect Med."},{"key":"2025010217184737400_fcae454-B2","doi-asserted-by":"crossref","first-page":"1577","DOI":"10.1016\/S0140-6736(20)32205-4","article-title":"Alzheimer\u2019s disease","volume":"397","author":"Scheltens","year":"2021","journal-title":"Lancet"},{"issue":"10","key":"2025010217184737400_fcae454-B3","doi-asserted-by":"crossref","first-page":"1183","DOI":"10.1038\/s41593-020-0687-6","article-title":"Synergy between amyloid-\u03b2 and tau in Alzheimer\u2019s disease","volume":"23","author":"Busche","year":"2020","journal-title":"Nat Neurosci"},{"issue":"3","key":"2025010217184737400_fcae454-B4","doi-asserted-by":"crossref","first-page":"349","DOI":"10.1038\/nn.3028","article-title":"The toxic A\u03b2 oligomer and Alzheimer\u2019s disease: An emperor in need of clothes","volume":"15","author":"Benilova","year":"2012","journal-title":"Nat Neurosci."},{"issue":"32","key":"2025010217184737400_fcae454-B5","doi-asserted-by":"crossref","first-page":"5870","DOI":"10.1523\/JNEUROSCI.0082-23.2023","article-title":"Tau and amyloid \u03b2 protein in patient-derived aqueous brain extracts act concomitantly to disrupt long-term potentiation in vivo","volume":"43","author":"Ondrejcak","year":"2023","journal-title":"J Neurosci"},{"key":"2025010217184737400_fcae454-B6","doi-asserted-by":"crossref","first-page":"105327","DOI":"10.1016\/j.nbd.2021.105327","article-title":"Single molecule imaging of protein aggregation in dementia: Methods, insights and prospects","volume":"153","author":"Danial","year":"2021","journal-title":"Neurobiol Dis."},{"key":"2025010217184737400_fcae454-B7","first-page":"369","article-title":"Cerebral organoids with chromosome 21 trisomy secrete Alzheimer\u2019s disease-related soluble aggregates detectable by single-molecule-fluorescence and super-resolution microscopy","volume":"15","author":"Fertan","year":"2023","journal-title":"Mol Psychiatry"},{"issue":"10","key":"2025010217184737400_fcae454-B8","doi-asserted-by":"crossref","first-page":"5766","DOI":"10.1038\/s41380-020-0806-5","article-title":"Patient-specific Alzheimer-like pathology in trisomy 21 cerebral organoids reveals BACE2 as a gene dose-sensitive AD suppressor in human brain","volume":"26","author":"Ali\u0107","year":"2021","journal-title":"Mol Psychiatry."},{"issue":"6","key":"2025010217184737400_fcae454-B9","doi-asserted-by":"crossref","first-page":"1039","DOI":"10.1016\/0092-8674(93)90312-E","article-title":"Cellular processing of beta-amyloid precursor protein and the genesis of amyloid beta-peptide","volume":"75","author":"Haass","year":"1993","journal-title":"Cell"},{"issue":"5","key":"2025010217184737400_fcae454-B10","doi-asserted-by":"crossref","first-page":"991","DOI":"10.1242\/jcs.109.5.991","article-title":"Trafficking of cell-surface amyloid \u03b2-protein precursor I. Secretion, endocytosis and recycling as detected by labeled monoclonal antibody","volume":"109","author":"Koo","year":"1996","journal-title":"J Cell Sci."},{"key":"2025010217184737400_fcae454-B11","doi-asserted-by":"crossref","first-page":"185","DOI":"10.1146\/annurev-neuro-061010-113613","article-title":"Amyloid precursor protein processing and Alzheimer\u2019s disease","volume":"34","author":"O\u2019Brien","year":"2011","journal-title":"Annu Rev Neurosci."},{"issue":"4","key":"2025010217184737400_fcae454-B12","doi-asserted-by":"crossref","first-page":"1179","DOI":"10.1523\/JNEUROSCI.21-04-01179.2001","article-title":"Beta-amyloid stimulation of microglia and monocytes results in TNFalpha-dependent expression of inducible nitric oxide synthase and neuronal apoptosis","volume":"21","author":"Combs","year":"2001","journal-title":"J Neurosci."},{"issue":"4\u20135","key":"2025010217184737400_fcae454-B13","doi-asserted-by":"crossref","first-page":"423","DOI":"10.1016\/S0736-5748(00)00012-5","article-title":"Induction of cytokines in glial cells surrounding cortical beta-amyloid plaques in transgenic Tg2576 mice with Alzheimer pathology","volume":"18","author":"Mehlhorn","year":"2000","journal-title":"Int J Dev Neurosci."},{"issue":"1","key":"2025010217184737400_fcae454-B14","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1016\/S0006-8993(00)03176-0","article-title":"Beta-amyloid-induced glial expression of both pro- and anti-inflammatory cytokines in cerebral cortex of aged transgenic Tg2576 mice with Alzheimer plaque pathology","volume":"894","author":"Apelt","year":"2001","journal-title":"Brain Res."},{"issue":"1","key":"2025010217184737400_fcae454-B15","doi-asserted-by":"crossref","first-page":"245","DOI":"10.1016\/j.yexcr.2004.01.002","article-title":"Interleukin-6 induces Alzheimer-type phosphorylation of tau protein by deregulating the cdk5\/p35 pathway","volume":"295","author":"Quintanilla","year":"2004","journal-title":"Exp Cell Res."},{"issue":"1","key":"2025010217184737400_fcae454-B16","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/s12974-021-02332-7","article-title":"Biologic TNF-\u03b1 inhibitors reduce microgliosis, neuronal loss, and tau phosphorylation in a transgenic mouse model of tauopathy","volume":"18","author":"Ou","year":"2021","journal-title":"J Neuroinflammation."},{"issue":"10","key":"2025010217184737400_fcae454-B17","first-page":"136","article-title":"Role of pro-inflammatory cytokines released from microglia in Alzheimer\u2019s disease","volume":"3","author":"Wang","year":"2015","journal-title":"Ann Transl Med."},{"issue":"1","key":"2025010217184737400_fcae454-B18","doi-asserted-by":"crossref","first-page":"229","DOI":"10.3233\/JAD-190835","article-title":"Age-related intraneuronal aggregation of amyloid-\u03b2 in endosomes, mitochondria, autophagosomes, and lysosomes","volume":"73","author":"Brewer","year":"2020","journal-title":"J Alzheimers Dis"},{"issue":"1","key":"2025010217184737400_fcae454-B19","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1016\/S0002-9440(10)64700-1","article-title":"Intraneuronal Abeta42 accumulation in human brain","volume":"156","author":"Gouras","year":"2000","journal-title":"Am J Pathol."},{"issue":"7","key":"2025010217184737400_fcae454-B20","doi-asserted-by":"crossref","first-page":"499","DOI":"10.1038\/nrn2168","article-title":"Intracellular amyloid-\u03b2 in Alzheimer\u2019s disease","volume":"8","author":"LaFerla","year":"2007","journal-title":"Nat Rev Neurosci."},{"issue":"8","key":"2025010217184737400_fcae454-B21","doi-asserted-by":"crossref","first-page":"2010","DOI":"10.3390\/molecules23082010","article-title":"A bifunctional anti-amyloid blocks oxidative stress and the accumulation of intraneuronal amyloid-beta","volume":"23","author":"Hilt","year":"2018","journal-title":"Molecules"},{"issue":"9","key":"2025010217184737400_fcae454-B22","doi-asserted-by":"crossref","first-page":"4656","DOI":"10.3390\/ijms23094656","article-title":"Role of intracellular amyloid \u03b2 as pathway modulator, biomarker, and therapy target","volume":"23","author":"Gallego Villarejo","year":"2022","journal-title":"Int J Mol Sci"},{"issue":"1","key":"2025010217184737400_fcae454-B23","doi-asserted-by":"crossref","first-page":"2043","DOI":"10.1038\/s41598-023-29248-x","article-title":"Noncanonical regulation of imprinted gene Igf2 by amyloid-beta 1\u201342 in Alzheimer\u2019s disease","volume":"13","author":"Fertan","year":"2023","journal-title":"Sci Rep."},{"issue":"1","key":"2025010217184737400_fcae454-B24","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1007\/s00401-018-1846-7","article-title":"Diffusible, highly bioactive oligomers represent a critical minority of soluble A\u03b2 in Alzheimer\u2019s disease brain","volume":"136","author":"Hong","year":"2018","journal-title":"Acta Neuropathol."},{"key":"2025010217184737400_fcae454-B25","doi-asserted-by":"crossref","first-page":"1108715","DOI":"10.3389\/fnins.2023.1108715","article-title":"Methods for the isolation and analysis of A\u03b2 from postmortem brain","volume":"17","author":"Hong","year":"2023","journal-title":"Front Neurosci"},{"key":"2025010217184737400_fcae454-B26","doi-asserted-by":"crossref","first-page":"595532","DOI":"10.3389\/fneur.2020.595532","article-title":"Tau post-translational modifications: Dynamic transformers of tau function, degradation, and aggregation","volume":"11","author":"Alquezar","year":"2021","journal-title":"Front Neurol"},{"issue":"2","key":"2025010217184737400_fcae454-B27","doi-asserted-by":"crossref","first-page":"361","DOI":"10.1152\/physrev.00024.2003","article-title":"Role of tau protein in both physiological and pathological conditions","volume":"84","author":"Avila","year":"2004","journal-title":"Physiol Rev."},{"issue":"1","key":"2025010217184737400_fcae454-B28","doi-asserted-by":"crossref","first-page":"fcz024","DOI":"10.1093\/braincomms\/fcz024","article-title":"Amyloid precursor protein processing in human neurons with an allelic series of the PSEN1 intron 4 deletion mutation and total presenilin-1 knockout","volume":"1","author":"Arber","year":"2019","journal-title":"Brain Commun."},{"issue":"11","key":"2025010217184737400_fcae454-B29","doi-asserted-by":"crossref","first-page":"2919","DOI":"10.1038\/s41380-019-0410-8","article-title":"Familial Alzheimer\u2019s disease patient-derived neurons reveal distinct mutation-specific effects on amyloid beta","volume":"25","author":"Arber","year":"2020","journal-title":"Mol Psychiatry."},{"issue":"13","key":"2025010217184737400_fcae454-B30","doi-asserted-by":"crossref","first-page":"3647","DOI":"10.1016\/j.celrep.2018.11.095","article-title":"Altered \u03b3-secretase processing of APP disrupts lysosome and autophagosome function in monogenic Alzheimer\u2019s disease","volume":"25","author":"Hung","year":"2018","journal-title":"Cell Rep."},{"issue":"13","key":"2025010217184737400_fcae454-B31","doi-asserted-by":"crossref","first-page":"5542","DOI":"10.1021\/ac300330g","article-title":"Selection of DNA aptamers that recognize \u03b1-synuclein oligomers using a competitive screening method","volume":"84","author":"Tsukakoshi","year":"2012","journal-title":"Anal Chem."},{"issue":"7","key":"2025010217184737400_fcae454-B32","doi-asserted-by":"crossref","first-page":"1405","DOI":"10.1016\/j.bbapap.2010.04.001","article-title":"Molecular mechanism of Thioflavin-T binding to amyloid fibrils","volume":"1804","author":"Biancalana","year":"2010","journal-title":"Biochim Biophys Acta."},{"issue":"2","key":"2025010217184737400_fcae454-B33","doi-asserted-by":"crossref","first-page":"fcaa146","DOI":"10.1093\/braincomms\/fcaa146","article-title":"Tumour necrosis factor induces increased production of extracellular amyloid-\u03b2- and \u03b1-synuclein-containing aggregates by human Alzheimer\u2019s disease neurons","volume":"2","author":"Whiten","year":"2020","journal-title":"Brain Commun."},{"issue":"7348","key":"2025010217184737400_fcae454-B34","doi-asserted-by":"crossref","first-page":"484","DOI":"10.1038\/nature10016","article-title":"Probing cellular protein complexes using single-molecule pull-down","volume":"473","author":"Jain","year":"2011","journal-title":"Nature"},{"issue":"1","key":"2025010217184737400_fcae454-B35","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1038\/s41467-022-33252-6","article-title":"Small soluble \u03b1-synuclein aggregates are the toxic species in Parkinson\u2019s disease","volume":"13","author":"Emin","year":"2022","journal-title":"Nat Commun."},{"issue":"3","key":"2025010217184737400_fcae454-B36","doi-asserted-by":"crossref","first-page":"fcab147","DOI":"10.1093\/braincomms\/fcab147","article-title":"Soluble amyloid beta-containing aggregates are present throughout the brain at early stages of Alzheimer\u2019s disease","volume":"3","author":"Sideris","year":"2021","journal-title":"Brain Commun."},{"issue":"6","key":"2025010217184737400_fcae454-B37","doi-asserted-by":"crossref","first-page":"1198","DOI":"10.1038\/nprot.2017.024","article-title":"Super-resolution microscopy with DNA-PAINT","volume":"12","author":"Schnitzbauer","year":"2017","journal-title":"Nat Protoc."},{"issue":"8","key":"2025010217184737400_fcae454-B38","doi-asserted-by":"crossref","first-page":"789","DOI":"10.1038\/s41592-020-0869-x","article-title":"Up to 100-fold speed-up and multiplexing in optimized DNA-PAINT","volume":"17","author":"Strauss","year":"2020","journal-title":"Nat Methods."},{"issue":"10","key":"2025010217184737400_fcae454-B39","doi-asserted-by":"crossref","first-page":"1836","DOI":"10.1038\/nprot.2012.116","article-title":"Directed differentiation of human pluripotent stem cells to cerebral cortex neurons and neural networks","volume":"7","author":"Shi","year":"2012","journal-title":"Nat Protoc"},{"issue":"7","key":"2025010217184737400_fcae454-B40","doi-asserted-by":"crossref","first-page":"499","DOI":"10.1021\/cn500105p","article-title":"New mouse model of Alzheimer\u2019s","volume":"5","author":"Nilsson","year":"2014","journal-title":"ACS Chem Neurosci"},{"issue":"12","key":"2025010217184737400_fcae454-B41","doi-asserted-by":"crossref","first-page":"3113","DOI":"10.1038\/s44321-024-00162-7","article-title":"APOE from astrocytes restores Alzheimer\u2019s A\u03b2-pathology and DAM-like responses in APOE deficient microglia","volume":"16","author":"Preman","year":"2024","journal-title":"EMBO Mol Med"},{"issue":"11","key":"2025010217184737400_fcae454-B42","doi-asserted-by":"crossref","first-page":"2570","DOI":"10.1038\/s41596-022-00730-6","article-title":"Constructing a cost-efficient, high-throughput and high-quality single-molecule localization microscope for super-resolution imaging","volume":"17","author":"Danial","year":"2022","journal-title":"Nat Protoc."},{"issue":"6","key":"2025010217184737400_fcae454-B43","doi-asserted-by":"crossref","first-page":"100499","DOI":"10.1016\/j.crmeth.2023.100499","article-title":"A computational suite for the structural and functional characterization of amyloid aggregates","volume":"3","author":"Xia","year":"2023","journal-title":"Cell Rep Methods."},{"issue":"8","key":"2025010217184737400_fcae454-B44","doi-asserted-by":"crossref","first-page":"711","DOI":"10.1038\/s41592-019-0472-1","article-title":"Quantitative analysis of super-resolved structures using ASAP","volume":"16","author":"Danial","year":"2019","journal-title":"Nat Methods."},{"key":"2025010217184737400_fcae454-B45","doi-asserted-by":"crossref","first-page":"e202317756","DOI":"10.1002\/anie.202317756","article-title":"Single-molecule characterization and super-resolution imaging of Alzheimer\u2019s disease-relevant tau aggregates in human samples","volume":"63","author":"B\u00f6ken","year":"2024","journal-title":"Angew Chem Int Ed Engl"},{"issue":"12","key":"2025010217184737400_fcae454-B46","doi-asserted-by":"crossref","first-page":"4002","DOI":"10.1172\/JCI36663","article-title":"Apoe isoform-specific disruption of amyloid beta peptide clearance from mouse brain","volume":"118","author":"Deane","year":"2008","journal-title":"J Clin Invest"},{"issue":"1","key":"2025010217184737400_fcae454-B47","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1111\/j.1365-2990.2012.01306.x","article-title":"Review: Microglia of the aged brain: Primed to be activated and resistant to regulation","volume":"39","author":"Norden","year":"2013","journal-title":"Neuropathol Appl Neurobiol."},{"issue":"1","key":"2025010217184737400_fcae454-B48","doi-asserted-by":"crossref","first-page":"699","DOI":"10.1186\/1742-2094-9-151","article-title":"Systemic immune challenges trigger and drive Alzheimer-like neuropathology in mice","volume":"9","author":"Krstic","year":"2012","journal-title":"J Neuroinflammation."},{"issue":"7","key":"2025010217184737400_fcae454-B49","doi-asserted-by":"crossref","first-page":"3926","DOI":"10.1007\/s00415-022-11036-8","article-title":"Familial British dementia: A clinical and multi-modal imaging case study","volume":"269","author":"Harris","year":"2022","journal-title":"J Neurol."},{"issue":"1","key":"2025010217184737400_fcae454-B50","doi-asserted-by":"crossref","first-page":"162","DOI":"10.1186\/s40478-021-01259-7","article-title":"Loss of presenilin function enhances tau phosphorylation and aggregation in mice","volume":"9","author":"Soto-Fagu\u00e1s","year":"2021","journal-title":"Acta Neuropathol Commun."},{"issue":"1","key":"2025010217184737400_fcae454-B51","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1186\/s13578-022-00874-8","article-title":"Presenilin-1 F105C mutation leads to tau accumulation in human neurons via the Akt\/mTORC1 signaling pathway","volume":"12","author":"Chong","year":"2022","journal-title":"Cell Biosci"},{"issue":"13","key":"2025010217184737400_fcae454-B52","doi-asserted-by":"crossref","first-page":"3523","DOI":"10.1093\/hmg\/ddu064","article-title":"The familial Alzheimer\u2019s disease APPV717I mutation alters APP processing and tau expression in iPSC-derived neurons","volume":"23","author":"Muratore","year":"2014","journal-title":"Hum Mol Genet"},{"key":"2025010217184737400_fcae454-B53","doi-asserted-by":"crossref","first-page":"463","DOI":"10.1111\/j.1749-6632.2002.tb04684.x","article-title":"Regulation of promoter activity of the APP gene by cytokines and growth factors: Implications in Alzheimer\u2019s disease","volume":"973","author":"Ge","year":"2002","journal-title":"Ann N Y Acad Sci."},{"issue":"2","key":"2025010217184737400_fcae454-B54","doi-asserted-by":"crossref","first-page":"680","DOI":"10.2353\/ajpath.2007.060378","article-title":"Interferon-gamma and tumor necrosis factor-alpha regulate amyloid-beta plaque deposition and beta-secretase expression in Swedish mutant APP transgenic mice","volume":"170","author":"Yamamoto","year":"2007","journal-title":"Am J Pathol."},{"issue":"1","key":"2025010217184737400_fcae454-B55","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1038\/nrrheum.2015.169","article-title":"TNF biology, pathogenic mechanisms and emerging therapeutic strategies","volume":"12","author":"Kalliolias","year":"2016","journal-title":"Nat Rev Rheumatol."},{"issue":"4","key":"2025010217184737400_fcae454-B56","doi-asserted-by":"crossref","first-page":"1603","DOI":"10.1021\/jacs.1c10173","article-title":"Kinetic modulation of amyloid-\u03b2 (1\u201342) aggregation and toxicity by structure-based rational design","volume":"144","author":"Im","year":"2022","journal-title":"J Am Chem Soc."},{"key":"2025010217184737400_fcae454-B57","doi-asserted-by":"crossref","first-page":"1","DOI":"10.2142\/biophysico.bppb-v19.0010","article-title":"Molecular dynamics simulations of amyloid-\u03b2 peptides in heterogeneous environments","volume":"19","author":"Tachi","year":"2022","journal-title":"Biophys Physicobiol."},{"key":"2025010217184737400_fcae454-B58","doi-asserted-by":"crossref","first-page":"42","DOI":"10.1016\/j.ebiom.2016.03.035","article-title":"The role of amyloid-\u03b2 oligomers in toxicity, propagation, and immunotherapy","volume":"6","author":"Sengupta","year":"2016","journal-title":"EBioMedicine"},{"key":"2025010217184737400_fcae454-B59","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1146\/annurev-biochem-061516-045115","article-title":"Amyloid formation, and human disease: A summary of progress over the last decade","volume":"86","author":"Chiti","year":"2017","journal-title":"Annu Rev Biochem."},{"issue":"1","key":"2025010217184737400_fcae454-B60","doi-asserted-by":"crossref","first-page":"1541","DOI":"10.1038\/s41467-019-09477-3","article-title":"Different soluble aggregates of A\u03b242 can give rise to cellular toxicity through different mechanisms","volume":"10","author":"De","year":"2019","journal-title":"Nat Commun."},{"key":"2025010217184737400_fcae454-B61","doi-asserted-by":"crossref","first-page":"972201","DOI":"10.3389\/fnins.2022.972201","article-title":"Large-scale organoid study suggests effects of trisomy 21 on early fetal neurodevelopment are more subtle than variability between isogenic lines and experiments","volume":"16","author":"Czerminski","year":"2023","journal-title":"Front Neurosci."},{"key":"2025010217184737400_fcae454-B62","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1016\/j.mcn.2018.03.015","article-title":"A\u03b2-oligomer uptake and the resulting inflammatory response in adult human astrocytes are precluded by an anti-A\u03b2 single chain variable fragment in combination with an apoE mimetic peptide","volume":"89","author":"Montoliu-Gaya","year":"2018","journal-title":"Mol Cell Neurosci."},{"issue":"1","key":"2025010217184737400_fcae454-B63","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1186\/1750-1326-6-45","article-title":"Microglial phagocytosis induced by fibrillar \u03b2-amyloid is attenuated by oligomeric \u03b2-amyloid: Implications for Alzheimer\u2019s disease","volume":"6","author":"Pan","year":"2011","journal-title":"Mol Neurodegener."},{"issue":"4","key":"2025010217184737400_fcae454-B64","doi-asserted-by":"crossref","first-page":"370","DOI":"10.1038\/nn1022","article-title":"Extracellular amyloid formation and associated pathology in neural grafts","volume":"6","author":"Meyer-Luehmann","year":"2003","journal-title":"Nat Neurosci."},{"issue":"1","key":"2025010217184737400_fcae454-B65","doi-asserted-by":"crossref","first-page":"66","DOI":"10.1111\/j.1750-3639.2005.tb00101.x","article-title":"Intracellular and extracellular Abeta, a tale of two neuropathologies","volume":"15","author":"Cuello","year":"2005","journal-title":"Brain Pathol"},{"issue":"7","key":"2025010217184737400_fcae454-B66","doi-asserted-by":"crossref","first-page":"1031","DOI":"10.1002\/jnr.22640","article-title":"Intraneuronal amyloid \u03b2 oligomers cause cell death via endoplasmic reticulum stress, endosomal\/lysosomal leakage, and mitochondrial dysfunction in vivo","volume":"89","author":"Umeda","year":"2011","journal-title":"J Neurosci Res"},{"issue":"6","key":"2025010217184737400_fcae454-B67","doi-asserted-by":"crossref","first-page":"691","DOI":"10.1002\/(SICI)1097-4547(19980615)52:6<691::AID-JNR8>3.0.CO;2-3","article-title":"Loss of endosomal\/lysosomal membrane impermeability is an early event in amyloid Abeta1\u201342 pathogenesis","volume":"52","author":"Yang","year":"1998","journal-title":"J Neurosci Res"},{"issue":"1","key":"2025010217184737400_fcae454-B68","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/s42466-021-00102-7","article-title":"Glymphatic system, AQP4, and their implications in Alzheimer\u2019s disease","volume":"3","author":"Silva","year":"2021","journal-title":"Neurol Res Pract."},{"issue":"4","key":"2025010217184737400_fcae454-B69","doi-asserted-by":"crossref","first-page":"603","DOI":"10.1016\/j.cell.2015.12.056","article-title":"The cellular phase of Alzheimer\u2019s disease","volume":"164","author":"De Strooper","year":"2016","journal-title":"Cell"},{"issue":"2","key":"2025010217184737400_fcae454-B70","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1016\/j.molmed.2007.12.002","article-title":"Amyloid beta, mitochondrial dysfunction and synaptic damage: Implications for cognitive decline in aging and Alzheimer\u2019s disease","volume":"14","author":"Reddy","year":"2008","journal-title":"Trends Mol Med"},{"issue":"7","key":"2025010217184737400_fcae454-B71","doi-asserted-by":"crossref","first-page":"1435","DOI":"10.1016\/j.ajpath.2019.03.006","article-title":"Cognitive decline, cerebral-spleen tryptophan metabolism, oxidative stress, cytokine production, and regulation of the txnip gene in a triple transgenic mouse model of Alzheimer disease","volume":"189","author":"Fertan","year":"2019","journal-title":"Am J Pathol."},{"issue":"3","key":"2025010217184737400_fcae454-B72","doi-asserted-by":"crossref","first-page":"e2217759120","DOI":"10.1073\/pnas.2217759120","article-title":"Cytosolic condensates rich in polyserine define subcellular sites of tau aggregation","volume":"120","author":"Lester","year":"2023","journal-title":"Proc Natl Acad Sci U S A"},{"issue":"30","key":"2025010217184737400_fcae454-B73","doi-asserted-by":"crossref","first-page":"10851","DOI":"10.1523\/JNEUROSCI.0387-15.2015","article-title":"C-Terminally truncated forms of tau, but not full-length tau or its C-terminal fragments, are released from neurons independently of cell death","volume":"35","author":"Kanmert","year":"2015","journal-title":"J Neurosci"},{"issue":"8","key":"2025010217184737400_fcae454-B74","doi-asserted-by":"crossref","first-page":"1954","DOI":"10.1038\/s41591-023-02443-z","article-title":"CSF MTBR-tau243 is a specific biomarker of tau tangle pathology in Alzheimer\u2019s disease","volume":"29","author":"Horie","year":"2023","journal-title":"Nat Med"},{"key":"2025010217184737400_fcae454-B75","doi-asserted-by":"crossref","first-page":"647054","DOI":"10.3389\/fnmol.2021.647054","article-title":"Tau: A signaling hub protein","volume":"14","author":"Mueller","year":"2021","journal-title":"Front Mol Neurosci"},{"issue":"12","key":"2025010217184737400_fcae454-B76","doi-asserted-by":"crossref","first-page":"946","DOI":"10.3390\/brainsci10120946","article-title":"Tau and DNA damage in neurodegeneration","volume":"10","author":"Colnaghi","year":"2020","journal-title":"Brain Sci"},{"issue":"47","key":"2025010217184737400_fcae454-B77","doi-asserted-by":"crossref","first-page":"49523","DOI":"10.1074\/jbc.M402034200","article-title":"Tumor necrosis factor-alpha, interleukin-1beta, and interferon-gamma stimulate gamma-secretase-mediated cleavage of amyloid precursor protein through a JNK-dependent MAPK pathway","volume":"279","author":"Liaoi","year":"2004","journal-title":"J Biol Chem."},{"issue":"3","key":"2025010217184737400_fcae454-B78","doi-asserted-by":"crossref","first-page":"1235","DOI":"10.3233\/JAD-180582","article-title":"Epitomic characterization of the specificity of the anti-amyloid A\u03b2 monoclonal antibodies 6E10 and 4G8","volume":"66","author":"Baghallab","year":"2018","journal-title":"J Alzheimers Dis"}],"container-title":["Brain Communications"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/braincomms\/advance-article-pdf\/doi\/10.1093\/braincomms\/fcae454\/61182943\/fcae454.pdf","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/braincomms\/article-pdf\/7\/1\/fcae454\/61182943\/fcae454.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/braincomms\/article-pdf\/7\/1\/fcae454\/61182943\/fcae454.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,1,2]],"date-time":"2025-01-02T17:20:03Z","timestamp":1735838403000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/braincomms\/article\/doi\/10.1093\/braincomms\/fcae454\/7924146"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,12,14]]},"references-count":78,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2024,12,24]]}},"URL":"https:\/\/doi.org\/10.1093\/braincomms\/fcae454","relation":{},"ISSN":["2632-1297"],"issn-type":[{"value":"2632-1297","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2025]]},"published":{"date-parts":[[2024,12,14]]},"article-number":"fcae454"}}