{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,6]],"date-time":"2026-11-06T12:46:41Z","timestamp":1793969201921,"version":"4.8.0"},"reference-count":106,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2024,12,5]],"date-time":"2024-12-05T00:00:00Z","timestamp":1733356800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Cell. Neurosci."],"abstract":"<jats:p>The pathophysiological role of A\u03b2<jats:sub>42<\/jats:sub> oligomers in the onset of Alzheimer\u2019s disease (AD) is heavily disputed, pivoting research toward investigating mixed oligomers composed of A\u03b2<jats:sub>42<\/jats:sub> and A\u03b2<jats:sub>40<\/jats:sub>, which is more abundant but less aggregation-prone. This study investigates A\u03b2<jats:sub>42<\/jats:sub>:A\u03b2<jats:sub>40<\/jats:sub> oligomers in different ratios, examining their adverse effects on endothelial cells, neurons, astroglia, and microglia, as well as in a human blood\u2013brain barrier (BBB) model. Combining label-free Raman microscopy with complementary imaging techniques and biochemical assays, we show the prominent impact of A\u03b2<jats:sub>40<\/jats:sub> on A\u03b2<jats:sub>42<\/jats:sub> fibrillation, suggesting an inhibitory effect on aggregation. Mixed oligomers, especially with low proportions of A\u03b2<jats:sub>42<\/jats:sub>, were equally detrimental as pure A\u03b2<jats:sub>42<\/jats:sub> oligomers regarding cell viability, functionality, and metabolism. They also differentially affected lipid droplet metabolism in BBB-associated microglia, indicating distinct pathophysiological responses. Our findings demonstrate the overarching significance of the A\u03b2<jats:sub>42<\/jats:sub>:A\u03b2<jats:sub>40<\/jats:sub> ratio in A\u03b2 oligomers, challenging the traditional focus on A\u03b2<jats:sub>42<\/jats:sub> in AD research.<\/jats:p>","DOI":"10.3389\/fncel.2024.1516093","type":"journal-article","created":{"date-parts":[[2024,12,9]],"date-time":"2024-12-09T10:01:19Z","timestamp":1733738479000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":8,"title":["The A\u03b242:A\u03b240 ratio modulates aggregation in beta-amyloid oligomers and drives metabolic changes and cellular dysfunction"],"prefix":"10.3389","volume":"18","author":[{"given":"Annika","family":"Haessler","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefanie","family":"Gier","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nathalie","family":"Jung","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maike","family":"Windbergs","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2024,12,5]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"983993","DOI":"10.3389\/fcell.2022.983993","article-title":"Decoding the role of cytochrome c in metabolism of human spermatozoa by Raman imaging","volume":"10","author":"Abramczyk","year":"2022","journal-title":"Front. 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Sci."},{"key":"ref9","doi-asserted-by":"publisher","first-page":"e41990","DOI":"10.1371\/journal.pone.0041990","article-title":"Mapping of redox state of mitochondrial cytochromes in live cardiomyocytes using Raman microspectroscopy","volume":"7","author":"Brazhe","year":"2012","journal-title":"PLoS One"},{"key":"ref10","doi-asserted-by":"publisher","first-page":"277","DOI":"10.3389\/fnagi.2017.00277","article-title":"Key aging-associated alterations in primary microglia response to Beta-amyloid stimulation","volume":"9","author":"Caldeira","year":"2017","journal-title":"Front. Aging Neurosci."},{"key":"ref11","doi-asserted-by":"publisher","first-page":"329","DOI":"10.1038\/s41419-023-05835-8","article-title":"Tunnelling nanotubes between neuronal and microglial cells allow bi-directional transfer of \u03b1-Synuclein and mitochondria","volume":"14","author":"Chakraborty","year":"2023","journal-title":"Cell Death Dis."},{"key":"ref12","doi-asserted-by":"publisher","first-page":"50842","DOI":"10.1074\/jbc.M207622200","article-title":"Early mitochondrial activation and cytochrome c up-regulation during apoptosis","volume":"277","author":"Chandra","year":"2002","journal-title":"J. Biol. Chem."},{"key":"ref13","doi-asserted-by":"publisher","first-page":"2674","DOI":"10.1111\/febs.12813","article-title":"The coexistence of an equal amount of Alzheimer\u2019s amyloid-\u03b2 40 and 42 forms structurally stable and toxic oligomers through a distinct pathway","volume":"281","author":"Chang","year":"2014","journal-title":"FEBS J."},{"key":"ref14","doi-asserted-by":"publisher","first-page":"137","DOI":"10.1016\/j.semcdb.2020.08.001","article-title":"Microglia and lipids: how metabolism controls brain innate immunity","volume":"112","author":"Chausse","year":"2021","journal-title":"Semin. Cell Dev. Biol."},{"key":"ref15","doi-asserted-by":"publisher","first-page":"84","DOI":"10.1016\/j.abb.2010.02.001","article-title":"Size-dependent neurotoxicity of beta-amyloid oligomers","volume":"496","author":"Cizas","year":"2010","journal-title":"Arch. Biochem. 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Neurodegener."},{"key":"ref19","doi-asserted-by":"publisher","first-page":"786","DOI":"10.1021\/acschemneuro.1c00784","article-title":"Taylor dispersion analysis and atomic force microscopy provide a quantitative insight into the aggregation kinetics of A\u03b2 (1-40)\/A\u03b2 (1-42) amyloid peptide mixtures","volume":"13","author":"Deleanu","year":"2022","journal-title":"ACS Chem. Neurosci."},{"key":"ref20","doi-asserted-by":"publisher","first-page":"32","DOI":"10.1186\/s13024-019-0333-5","article-title":"The neuropathological diagnosis of Alzheimer\u2019s disease","volume":"14","author":"DeTure","year":"2019","journal-title":"Mol. Neurodegener."},{"key":"ref21","doi-asserted-by":"publisher","first-page":"166246","DOI":"10.1016\/j.bbadis.2021.166246","article-title":"Amyloid-\u03b2 induced membrane damage instigates tunneling nanotube-like conduits by p21-activated kinase dependent actin remodulation","volume":"1867","author":"Dilna","year":"2021","journal-title":"Biochim. Biophys. Acta Mol. basis Dis."},{"key":"ref22","doi-asserted-by":"publisher","first-page":"23935","DOI":"10.1038\/s41598-021-03442-1","article-title":"Optimised techniques for high-throughput screening of differentiated SH-SY5Y cells and application for neurite outgrowth assays","volume":"11","author":"Dravid","year":"2021","journal-title":"Sci. Rep."},{"key":"ref23","doi-asserted-by":"publisher","first-page":"991","DOI":"10.1046\/j.1471-4159.2000.0750991.x","article-title":"Sequential treatment of SH-SY5Y cells with retinoic acid and brain-derived neurotrophic factor gives rise to fully differentiated, neurotrophic factor-dependent, human neuron-like cells","volume":"75","author":"Encinas","year":"2000","journal-title":"J. Neurochem."},{"key":"ref24","doi-asserted-by":"publisher","first-page":"742","DOI":"10.3389\/fnins.2020.00742","article-title":"Lipid Droplets in Neurodegenerative Disorders","volume":"14","author":"Farmer","year":"2020","journal-title":"Front. Neurosci."},{"key":"ref25","doi-asserted-by":"publisher","first-page":"41","DOI":"10.1186\/s12860-014-0041-5","article-title":"A thin layer angiogenesis assay: a modified basement matrix assay for assessment of endothelial cell differentiation","volume":"15","author":"Faulkner","year":"2014","journal-title":"BMC Cell Biol."},{"key":"ref26","doi-asserted-by":"publisher","first-page":"6983","DOI":"10.1039\/c8cc03217c","article-title":"Raman fingerprints of amyloid structures","volume":"54","author":"Flynn","year":"2018","journal-title":"Chem. 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Res."},{"key":"ref32","doi-asserted-by":"publisher","first-page":"1060","DOI":"10.1111\/j.1471-4159.2012.07660.x","article-title":"Saturated long-chain fatty acids activate inflammatory signaling in astrocytes","volume":"120","author":"Gupta","year":"2012","journal-title":"J. Neurochem."},{"key":"ref33","doi-asserted-by":"publisher","first-page":"102","DOI":"10.1038\/s41586-021-03960-y","article-title":"Neurotoxic reactive astrocytes induce cell death via saturated lipids","volume":"599","author":"Guttenplan","year":"2021","journal-title":"Nature"},{"key":"ref34","doi-asserted-by":"publisher","first-page":"5481","DOI":"10.1038\/s41380-021-01249-0","article-title":"The amyloid-\u03b2 pathway in Alzheimer\u2019s disease","volume":"26","author":"Hampel","year":"2021","journal-title":"Mol. 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Neurosci."},{"key":"ref38","doi-asserted-by":"publisher","first-page":"4477","DOI":"10.3390\/ijms21124477","article-title":"The toxicity and polymorphism of \u03b2-amyloid oligomers","volume":"21","author":"Huang","year":"2020","journal-title":"Int. J. Mol. Sci."},{"key":"ref39","doi-asserted-by":"publisher","first-page":"181483","DOI":"10.1098\/rsos.181483","article-title":"Ratiometric analysis using Raman spectroscopy as a powerful predictor of structural properties of fatty acids","volume":"5","author":"Jamieson","year":"2018","journal-title":"R. Soc. Open Sci."},{"key":"ref40","doi-asserted-by":"publisher","first-page":"28176","DOI":"10.1074\/jbc.M803159200","article-title":"The ratio of monomeric to aggregated forms of Abeta40 and Abeta42 is an important determinant of amyloid-beta aggregation, fibrillogenesis, and toxicity","volume":"283","author":"Jan","year":"2008","journal-title":"J. Biol. Chem."},{"key":"ref41","doi-asserted-by":"publisher","first-page":"5415","DOI":"10.1039\/D1BM00597A","article-title":"Non-invasive analysis of pancreas organoids in synthetic hydrogels defines material-cell interactions and luminal composition","volume":"9","author":"Jung","year":"2021","journal-title":"Biomater. Sci."},{"key":"ref42","doi-asserted-by":"publisher","first-page":"2651","DOI":"10.1016\/j.immuni.2024.09.014","article-title":"Apolipoprotein E aggregation in microglia initiates Alzheimer\u2019s disease pathology by seeding \u03b2-amyloidosis","volume":"57","author":"Kaji","year":"2024","journal-title":"Immunity"},{"key":"ref43","doi-asserted-by":"publisher","first-page":"876","DOI":"10.1038\/s41593-022-01104-7","article-title":"A shared disease-associated oligodendrocyte signature among multiple CNS pathologies","volume":"25","author":"Kenigsbuch","year":"2022","journal-title":"Nat. Neurosci."},{"key":"ref44","doi-asserted-by":"publisher","first-page":"607","DOI":"10.1016\/j.bbalip.2012.01.007","article-title":"Dynamics and regulation of lipid droplet formation in lipopolysaccharide (LPS)-stimulated microglia","volume":"1821","author":"Khatchadourian","year":"2012","journal-title":"Biochim. Biophys. Acta"},{"key":"ref45","doi-asserted-by":"publisher","first-page":"686","DOI":"10.14283\/jpad.2023.109","article-title":"Neuroinflammation, its role in Alzheimer\u2019s disease and therapeutic Strategie","volume":"10","author":"Kiraly","year":"2023","journal-title":"J. Prev Alzheimers Dis."},{"key":"ref46","doi-asserted-by":"publisher","first-page":"848215","DOI":"10.3389\/fnins.2022.848215","article-title":"ACU193: an immunotherapeutic poised to test the amyloid \u03b2 oligomer hypothesis of Alzheimer\u2019s disease","volume":"16","author":"Krafft","year":"2022","journal-title":"Front. Neurosci."},{"key":"ref47","doi-asserted-by":"publisher","first-page":"7826","DOI":"10.1038\/s41598-019-44346-5","article-title":"Stress-induced tunneling nanotubes support treatment adaptation in prostate cancer","volume":"9","author":"Kretschmer","year":"2019","journal-title":"Sci. Rep."},{"key":"ref48","doi-asserted-by":"publisher","first-page":"e0186636","DOI":"10.1371\/journal.pone.0186636","article-title":"In situ fibrillizing amyloid-beta 1-42 induces neurite degeneration and apoptosis of differentiated SH-SY5Y cells","volume":"12","author":"Krishtal","year":"2017","journal-title":"PLoS One"},{"key":"ref49","doi-asserted-by":"publisher","first-page":"119712","DOI":"10.1016\/j.saa.2021.119712","article-title":"Potential of Raman spectroscopic techniques to study proteins","volume":"258","author":"Kuhar","year":"2021","journal-title":"Spectrochim. Acta A"},{"key":"ref50","doi-asserted-by":"publisher","first-page":"3408","DOI":"10.1038\/emboj.2010.211","article-title":"Neurotoxicity of Alzheimer\u2019s disease A\u03b2 peptides is induced by small changes in the A\u03b242 to A\u03b240 ratio","volume":"29","author":"Kuperstein","year":"2010","journal-title":"EMBO J."},{"key":"ref51","doi-asserted-by":"publisher","first-page":"1377","DOI":"10.1038\/s41467-020-15120-3","article-title":"Amyloid-\u03b242\/40 ratio drives tau pathology in 3D human neural cell culture models of Alzheimer\u2019s disease","volume":"11","author":"Kwak","year":"2020","journal-title":"Nat. Commun."},{"key":"ref52","doi-asserted-by":"publisher","first-page":"359","DOI":"10.1177\/0003702818819880","article-title":"Two-dimensional correlation spectroscopy (2D-COS) for analysis of spatially resolved vibrational spectra","volume":"73","author":"Lasch","year":"2019","journal-title":"J. Appl. Spectrosc."},{"key":"ref53","doi-asserted-by":"publisher","first-page":"6627","DOI":"10.1523\/JNEUROSCI.0203-11.2011","article-title":"Soluble A\u03b2 oligomers inhibit long-term potentiation through a mechanism involving excessive activation of extrasynaptic NR2B-containing NMDA receptors","volume":"31","author":"Li","year":"2011","journal-title":"J. Neurosci."},{"key":"ref54","doi-asserted-by":"publisher","first-page":"402","DOI":"10.1006\/meth.2001.1262","article-title":"Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) method","volume":"25","author":"Livak","year":"2001","journal-title":"Methods"},{"key":"ref55","doi-asserted-by":"publisher","first-page":"393","DOI":"10.3389\/fphys.2020.00393","article-title":"Lipid and lipoprotein metabolism in microglia","volume":"11","author":"Loving","year":"2020","journal-title":"Front. Physiol."},{"key":"ref56","doi-asserted-by":"publisher","first-page":"158","DOI":"10.1021\/acsbiomedchemau.2c00067","article-title":"Controlling amyloid Beta peptide aggregation and toxicity by protease-stable ligands","volume":"3","author":"Mallesh","year":"2023","journal-title":"ACS Bio Med Chem Au"},{"key":"ref57","doi-asserted-by":"publisher","first-page":"914","DOI":"10.1111\/acel.12500","article-title":"Beta-amyloid 1-42 monomers, but not oligomers, produce PHF-like conformation of tau protein","volume":"15","author":"Manassero","year":"2016","journal-title":"Aging Cell"},{"key":"ref58","doi-asserted-by":"publisher","first-page":"218","DOI":"10.1186\/s13014-019-1416-8","article-title":"Perspectives of cellular communication through tunneling nanotubes in cancer cells and the connection to radiation effects","volume":"14","author":"Matejka","year":"2019","journal-title":"Radiat. Oncol."},{"key":"ref59","doi-asserted-by":"publisher","first-page":"21","DOI":"10.1186\/s12974-016-0484-z","article-title":"Characterization of a novel adult murine immortalized microglial cell line and its activation by amyloid-beta","volume":"13","author":"McCarthy","year":"2016","journal-title":"J. Neuroinflammation"},{"key":"ref60","doi-asserted-by":"publisher","first-page":"167","DOI":"10.1002\/cyto.a.20022","article-title":"Design and validation of a tool for neurite tracing and analysis in fluorescence microscopy images","author":"Meijering","year":"2004","journal-title":"Cytometry A"},{"key":"ref61","doi-asserted-by":"publisher","first-page":"910","DOI":"10.1002\/jrs.5149","article-title":"Raman optical activity of human \u03b1 -synuclein in intrinsically disordered, micelle-bound \u03b1 -helical, molten globule and oligomeric \u03b2 -sheet state","volume":"48","author":"Mensch","year":"2017","journal-title":"J. Raman Spectrosc."},{"key":"ref62","doi-asserted-by":"publisher","first-page":"59","DOI":"10.3389\/fnint.2013.00059","article-title":"Inflammatory process in Alzheimer\u2019s disease","volume":"7","author":"Meraz-R\u00edos","year":"2013","journal-title":"Front. Integr. Neurosci."},{"key":"ref63","doi-asserted-by":"publisher","first-page":"2","DOI":"10.1016\/j.bbadis.2009.10.006","article-title":"Mitochondrial dysfunction is a trigger of Alzheimer\u2019s disease pathophysiology","volume":"1802","author":"Moreira","year":"2010","journal-title":"Biochim. Biophys. Acta"},{"key":"ref64","doi-asserted-by":"publisher","first-page":"493","DOI":"10.1080\/05704920701551530","article-title":"Raman spectroscopy of biological tissues","volume":"42","author":"Movasaghi","year":"2007","journal-title":"Appl. Spectrosc. Rev."},{"key":"ref65","doi-asserted-by":"publisher","first-page":"3105","DOI":"10.3390\/biomedicines10123105","article-title":"Microglia and cholesterol handling: implications for Alzheimer\u2019s disease","volume":"10","author":"Mu\u00f1oz Herrera","year":"2022","journal-title":"Biomedicines"},{"key":"ref66","doi-asserted-by":"publisher","first-page":"157","DOI":"10.1016\/j.ab.2006.03.025","article-title":"Validation of the drop coating deposition Raman method for protein analysis","volume":"353","author":"Ortiz","year":"2006","journal-title":"Anal. Biochem."},{"key":"ref67","doi-asserted-by":"publisher","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."},{"key":"ref68","doi-asserted-by":"publisher","first-page":"75","DOI":"10.1023\/B:AGEN.0000037335.17717.bf","article-title":"Inhibition of angiogenesis by Abeta peptides","volume":"7","author":"Paris","year":"2004","journal-title":"Angiogenesis"},{"key":"ref69","doi-asserted-by":"publisher","first-page":"e13258","DOI":"10.1111\/acel.13258","article-title":"Alzheimer\u2019s amyloid \u03b2 heterogeneous species differentially affect brain endothelial cell viability, blood-brain barrier integrity, and angiogenesis","volume":"19","author":"Parodi-Rull\u00e1n","year":"2020","journal-title":"Aging Cell"},{"key":"ref70","first-page":"31","article-title":"Protein secondary structure determination using drop coat deposition confocal Raman spectroscopy","volume":"31","author":"Peters","year":"2016","journal-title":"Spectroscopy"},{"key":"ref71","doi-asserted-by":"publisher","first-page":"90","DOI":"10.1093\/brain\/awm260","article-title":"The beta-amyloid protein of Alzheimer\u2019s disease increases neuronal CRMP-2 phosphorylation by a rho-GTP mechanism","volume":"131","author":"Petratos","year":"2008","journal-title":"Brain"},{"key":"ref72","doi-asserted-by":"publisher","first-page":"2348","DOI":"10.1002\/jrs.6204","article-title":"Raman spectroscopy in cell biology and microbiology","volume":"52","author":"Pezzotti","year":"2021","journal-title":"J. Raman Spectrosc."},{"key":"ref73","doi-asserted-by":"publisher","first-page":"22","DOI":"10.1186\/s40035-017-0091-7","article-title":"The role of amyloid beta clearance in cerebral amyloid angiopathy: more potential therapeutic targets","volume":"6","author":"Qi","year":"2017","journal-title":"Transl. Neurodegener."},{"key":"ref74","doi-asserted-by":"publisher","first-page":"2136","DOI":"10.1083\/jcb.202102136","article-title":"Lipid droplets in the nervous system","volume":"220","author":"Ralhan","year":"2021","journal-title":"J. Cell Biol."},{"key":"ref75","doi-asserted-by":"publisher","first-page":"1486","DOI":"10.1093\/brain\/awx057","article-title":"Biochemically-defined pools of amyloid-\u03b2 in sporadic Alzheimer\u2019s disease: correlation with amyloid PET","volume":"140","author":"Roberts","year":"2017","journal-title":"Brain"},{"key":"ref76","doi-asserted-by":"publisher","first-page":"1208","DOI":"10.1177\/0003702819858671","article-title":"Key role of cytochrome C for apoptosis detection using Raman microimaging in an animal model of brain ischemia with insulin treatment","volume":"73","author":"Russo","year":"2019","journal-title":"J. Appl. Spectrosc."},{"key":"ref77","doi-asserted-by":"publisher","first-page":"1061","DOI":"10.1002\/jrs.4335","article-title":"Raman spectroscopy of proteins: a review","volume":"44","author":"Rygula","year":"2013","journal-title":"J. Raman Spectrosc."},{"key":"ref78","doi-asserted-by":"publisher","first-page":"196","DOI":"10.1186\/s13195-022-01141-1","article-title":"A\u03b242 oligomer-specific antibody ALZ-201 reduces the neurotoxicity of Alzheimer\u2019s disease brain extracts","volume":"14","author":"Sandberg","year":"2022","journal-title":"Alzheimers Res. Ther."},{"key":"ref79","doi-asserted-by":"publisher","first-page":"1668","DOI":"10.1038\/s41593-024-01730-3","article-title":"Oligodendrocytes produce amyloid-\u03b2 and contribute to plaque formation alongside neurons in Alzheimer\u2019s disease model mice","volume":"27","author":"Sasmita","year":"2024","journal-title":"Nat. Neurosci."},{"key":"ref80","doi-asserted-by":"publisher","first-page":"676","DOI":"10.1038\/nmeth.2019","article-title":"Fiji: an open-source platform for biological-image analysis","volume":"9","author":"Schindelin","year":"2012","journal-title":"Nat. Methods"},{"key":"ref81","doi-asserted-by":"publisher","first-page":"4634","DOI":"10.1038\/s41467-021-24900-4","article-title":"Endo-lysosomal A\u03b2 concentration and pH trigger formation of A\u03b2 oligomers that potently induce tau missorting","volume":"12","author":"Sch\u00fctzmann","year":"2021","journal-title":"Nat. Commun."},{"key":"ref82","doi-asserted-by":"publisher","first-page":"53193","DOI":"10.3791\/53193","article-title":"Differentiation of the SH-SY5Y human neuroblastoma cell line","volume":"108","author":"Shipley","year":"2016","journal-title":"J. Vis. Exp."},{"key":"ref83","doi-asserted-by":"publisher","first-page":"4564","DOI":"10.1126\/scitranslmed.aaz4564","article-title":"APOE4 disrupts intracellular lipid homeostasis in human iPSC-derived glia","volume":"13","author":"Sienski","year":"2021","journal-title":"Sci. Transl. Med."},{"key":"ref84","doi-asserted-by":"publisher","first-page":"206","DOI":"10.1186\/s12974-022-02565-0","article-title":"Astrocytic and microglial cells as the modulators of neuroinflammation in Alzheimer\u2019s disease","volume":"19","author":"Singh","year":"2022","journal-title":"J. Neuroinflammation"},{"key":"ref85","doi-asserted-by":"publisher","first-page":"1179","DOI":"10.3233\/JAD-200473","article-title":"Alzheimer\u2019s disease: the link between amyloid-\u03b2 and neurovascular dysfunction","volume":"76","author":"Solis","year":"2020","journal-title":"J. Alzheimers Dis."},{"key":"ref86","doi-asserted-by":"publisher","first-page":"3758","DOI":"10.1038\/s41467-019-11674-z","article-title":"Sustained microglial depletion with CSF1R inhibitor impairs parenchymal plaque development in an Alzheimer\u2019s disease model","volume":"10","author":"Spangenberg","year":"2019","journal-title":"Nat. Commun."},{"key":"ref87","doi-asserted-by":"publisher","first-page":"13","DOI":"10.1007\/978-1-60761-744-0_2","article-title":"Preparing synthetic A\u03b2 in different aggregation states","volume":"670","author":"Stine","year":"2011","journal-title":"Methods Mol. Biol."},{"key":"ref88","doi-asserted-by":"publisher","first-page":"697","DOI":"10.1016\/j.bbamem.2018.11.013","article-title":"The role of membrane trafficking in the processing of amyloid precursor protein and production of amyloid peptides in Alzheimer\u2019s disease","volume":"1861","author":"Tan","year":"2019","journal-title":"Biochim. Biophys. Acta Biomembr."},{"key":"ref89","doi-asserted-by":"publisher","first-page":"830","DOI":"10.3390\/biom13050830","article-title":"Microvascular contributions to Alzheimer disease pathogenesis: is Alzheimer disease primarily an Endotheliopathy?","volume":"13","author":"Tarawneh","year":"2023","journal-title":"Biomol. Ther."},{"key":"ref90","doi-asserted-by":"publisher","first-page":"1058","DOI":"10.1007\/s11626-024-00948-6","article-title":"Differentiation of SH-SY5Y neuroblastoma cells using retinoic acid and BDNF: a model for neuronal and synaptic differentiation in neurodegeneration","volume":"60","author":"Targett","year":"2024","journal-title":"In Vitro Cell. Dev. Biol. Anim."},{"key":"ref91","doi-asserted-by":"publisher","first-page":"46","DOI":"10.1186\/s12964-017-0201-2","article-title":"A transwell assay that excludes exosomes for assessment of tunneling nanotube-mediated intercellular communication","volume":"15","author":"Thayanithy","year":"2017","journal-title":"Cell Commun. Signal"},{"key":"ref92","doi-asserted-by":"publisher","first-page":"846","DOI":"10.3791\/55846","article-title":"In vitro assays to assess blood-brain barrier mesh-like vessel formation and disruption","volume":"124","author":"Thomas","year":"2017","journal-title":"J. Vis. Exp."},{"key":"ref93","doi-asserted-by":"publisher","first-page":"25841","DOI":"10.1038\/srep25841","article-title":"Amyloid beta oligomers induce neuronal elasticity changes in age-dependent manner: a force spectroscopy study on living hippocampal neurons","volume":"6","author":"Ungureanu","year":"2016","journal-title":"Sci. Rep."},{"key":"ref94","doi-asserted-by":"publisher","first-page":"3490","DOI":"10.1002\/1873-3468.13919","article-title":"Internalisation and toxicity of amyloid-\u03b2 1-42 are influenced by its conformation and assembly state rather than size","volume":"594","author":"Vadukul","year":"2020","journal-title":"FEBS Lett."},{"key":"ref95","doi-asserted-by":"publisher","first-page":"1181","DOI":"10.1038\/cdd.2014.211","article-title":"Transfer of mitochondria via tunneling nanotubes rescues apoptotic PC12 cells","volume":"22","author":"Wang","year":"2015","journal-title":"Cell Death Differ."},{"key":"ref96","doi-asserted-by":"publisher","first-page":"2091","DOI":"10.3390\/cells11132091","article-title":"Microglia phenotypes in aging and neurodegenerative diseases","volume":"11","author":"Wendimu","year":"2022","journal-title":"Cells"},{"key":"ref97","doi-asserted-by":"publisher","first-page":"266","DOI":"10.1117\/12.366289","article-title":"N-FINDR: an algorithm for fast autonomous spectral end-member determination in hyperspectral data","volume":"3753","author":"Winter","year":"1999","journal-title":"Imaging Spectrom. V"},{"key":"ref98","doi-asserted-by":"publisher","first-page":"1420","DOI":"10.1111\/febs.16344","article-title":"Lipid metabolism and Alzheimer\u2019s disease: clinical evidence, mechanistic link and therapeutic promise","volume":"290","author":"Yin","year":"2023","journal-title":"FEBS J."},{"key":"ref99","doi-asserted-by":"publisher","first-page":"1427","DOI":"10.1002\/pro.3434","article-title":"Surface enhanced Raman spectroscopy distinguishes amyloid \u0392-protein isoforms and conformational states","volume":"27","author":"Yu","year":"2018","journal-title":"Protein Sci."},{"key":"ref100","doi-asserted-by":"publisher","first-page":"105","DOI":"10.1016\/j.ceb.2021.07.007","article-title":"Microglial \u2018fat shaming\u2019 in development and disease","volume":"73","author":"Zareba","year":"2021","journal-title":"Curr. Opin. Cell Biol."},{"key":"ref101","doi-asserted-by":"publisher","first-page":"248","DOI":"10.1038\/s41392-023-01484-7","article-title":"Amyloid \u03b2-based therapy for Alzheimer\u2019s disease: challenges, successes and future","volume":"8","author":"Zhang","year":"2023","journal-title":"Sig. Transduct. Target. Ther."},{"key":"ref102","doi-asserted-by":"publisher","first-page":"1808","DOI":"10.3390\/biom12121808","article-title":"Different extracellular \u03b2-amyloid (1-42) aggregates differentially impair neural cell adhesion and neurite outgrowth through differential induction of scaffold Palladin","volume":"12","author":"Zhang","year":"2022","journal-title":"Biomol. Ther."},{"key":"ref103","first-page":"12509","article-title":"Intercellular transport of tau protein and \u03b2-amyloid mediated by tunneling nanotubes","volume":"13","author":"Zhang","year":"2021","journal-title":"Am. J. Transl. Res."},{"key":"ref104","doi-asserted-by":"publisher","first-page":"154","DOI":"10.1159\/000535131","article-title":"Brain lipids and lipid droplet dysregulation in Alzheimer\u2019s disease and neuropsychiatric disorders","volume":"9","author":"Zhao","year":"2023","journal-title":"Complex Psychiatry"},{"key":"ref105","doi-asserted-by":"publisher","first-page":"125","DOI":"10.1080\/19336896.2015.1025189","article-title":"Prion aggregates transfer through tunneling nanotubes in endocytic vesicles","volume":"9","author":"Zhu","year":"2015","journal-title":"Prion"},{"key":"ref106","doi-asserted-by":"publisher","first-page":"329","DOI":"10.2119\/molmed.2016.00127","article-title":"Interrelationship between changes in the amyloid \u03b2 42\/40 ratio and Presenilin 1 conformation","volume":"22","author":"Zoltowska","year":"2016","journal-title":"Mol. 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