{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T02:29:37Z","timestamp":1791944977467,"version":"4.3.4"},"reference-count":80,"publisher":"Oxford University Press (OUP)","issue":"1","license":[{"start":{"date-parts":[[2020,11,27]],"date-time":"2020-11-27T00:00:00Z","timestamp":1606435200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"NIH","doi-asserted-by":"publisher","award":["R01 AG066429"],"award-info":[{"award-number":["R01 AG066429"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"NIH","doi-asserted-by":"publisher","award":["RF1 AG054199"],"award-info":[{"award-number":["RF1 AG054199"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"NIH","doi-asserted-by":"publisher","award":["R01 AG054672"],"award-info":[{"award-number":["R01 AG054672"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"NIH","doi-asserted-by":"publisher","award":["R56 AG057469"],"award-info":[{"award-number":["R56 AG057469"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"NIH","doi-asserted-by":"publisher","award":["R21 NS104609"],"award-info":[{"award-number":["R21 NS104609"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"NIH","doi-asserted-by":"publisher","award":["R01AG054025"],"award-info":[{"award-number":["R01AG054025"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"NIH","doi-asserted-by":"publisher","award":["R01NS094557"],"award-info":[{"award-number":["R01NS094557"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000957","name":"Alzheimer\u2019s Association","doi-asserted-by":"crossref","award":["AARF-9550302678"],"award-info":[{"award-number":["AARF-9550302678"]}],"id":[{"id":"10.13039\/100000957","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100007625","name":"Cure Alzheimer\u2019s Fund","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100007625","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100006312","name":"BrightFocus Foundation","doi-asserted-by":"publisher","award":["A2016551S"],"award-info":[{"award-number":["A2016551S"]}],"id":[{"id":"10.13039\/100006312","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100008539","name":"CurePSP","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100008539","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"NIH","doi-asserted-by":"publisher","award":["P30 AG013846"],"award-info":[{"award-number":["P30 AG013846"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2021,2,12]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Extracellular vesicles are highly transmissible and play critical roles in the propagation of tau pathology, although the underlying mechanism remains elusive. Here, for the first time, we comprehensively characterized the physicochemical structure and pathogenic function of human brain-derived extracellular vesicles isolated from Alzheimer\u2019s disease, prodromal Alzheimer\u2019s disease, and non-demented control cases. Alzheimer\u2019s disease extracellular vesicles were significantly enriched in epitope-specific tau oligomers in comparison to prodromal Alzheimer\u2019s disease or control extracellular vesicles as determined by dot blot and atomic force microscopy. Alzheimer\u2019s disease extracellular vesicles were more efficiently internalized by murine cortical neurons, as well as more efficient in transferring and misfolding tau, than prodromal Alzheimer\u2019s disease and control extracellular vesicles in vitro. Strikingly, the inoculation of Alzheimer\u2019s disease or prodromal Alzheimer\u2019s disease extracellular vesicles containing only 300 pg of tau into the outer molecular layer of the dentate gyrus of 18-month-old C57BL\/6 mice resulted in the accumulation of abnormally phosphorylated tau throughout the hippocampus by 4.5 months, whereas inoculation of an equal amount of tau from control extracellular vesicles, isolated tau oligomers, or fibrils from the same Alzheimer\u2019s disease donor showed little tau pathology. Furthermore, Alzheimer\u2019s disease extracellular vesicles induced misfolding of endogenous tau in both oligomeric and sarkosyl-insoluble forms in the hippocampal region. Unexpectedly, phosphorylated tau was primarily accumulated in glutamic acid decarboxylase 67 (GAD67) GABAergic interneurons and, to a lesser extent, glutamate receptor 2\/3-positive excitatory mossy cells, showing preferential extracellular vesicle-mediated GABAergic interneuronal tau propagation. Whole-cell patch clamp recordings of CA1 pyramidal cells showed significant reduction in the amplitude of spontaneous inhibitory post-synaptic currents. This was accompanied by reductions in c-fos+ GAD67+ neurons and GAD67+ neuronal puncta surrounding pyramidal neurons in the CA1 region, confirming reduced GABAergic transmission in this region. Our study posits a novel mechanism for the spread of tau in hippocampal GABAergic interneurons via brain-derived extracellular vesicles and their subsequent neuronal dysfunction.<\/jats:p>","DOI":"10.1093\/brain\/awaa376","type":"journal-article","created":{"date-parts":[[2020,10,7]],"date-time":"2020-10-07T15:13:48Z","timestamp":1602083628000},"page":"288-309","source":"Crossref","is-referenced-by-count":284,"title":["Alzheimer\u2019s disease brain-derived extracellular vesicles spread tau pathology in interneurons"],"prefix":"10.1093","volume":"144","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3587-9425","authenticated-orcid":false,"given":"Zhi","family":"Ruan","sequence":"first","affiliation":[{"name":"Department of Pharmacology and Experimental Therapeutics, Boston University School of Medicine, Boston, MA 02118, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dhruba","family":"Pathak","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Experimental Therapeutics, Boston University School of Medicine, Boston, MA 02118, USA"},{"name":"Department of Anatomy and Neurobiology, Boston University School of Medicine, Boston, MA 02118, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Srinidhi","family":"Venkatesan Kalavai","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Experimental Therapeutics, Boston University School of Medicine, Boston, MA 02118, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Asuka","family":"Yoshii-Kitahara","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Experimental Therapeutics, Boston University School of Medicine, Boston, MA 02118, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Satoshi","family":"Muraoka","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Experimental Therapeutics, Boston University School of Medicine, Boston, MA 02118, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nemil","family":"Bhatt","sequence":"additional","affiliation":[{"name":"Department of Neurology, University of Texas Medical Branch, Galveston, TX 77555, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kayo","family":"Takamatsu-Yukawa","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Experimental Therapeutics, Boston University School of Medicine, Boston, MA 02118, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianqiao","family":"Hu","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Experimental Therapeutics, Boston University School of Medicine, Boston, MA 02118, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuzhi","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Experimental Therapeutics, Boston University School of Medicine, Boston, MA 02118, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Samuel","family":"Hersh","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Experimental Therapeutics, Boston University School of Medicine, Boston, MA 02118, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria","family":"Ericsson","sequence":"additional","affiliation":[{"name":"Department of Cell Biology, Harvard Medical School, Boston, MA 02115, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Santhi","family":"Gorantla","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Experimental Neurosciences, University of Nebraska Medical Center, Omaha, NE 68198, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Howard E","family":"Gendelman","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Experimental Neurosciences, University of Nebraska Medical Center, Omaha, NE 68198, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rakez","family":"Kayed","sequence":"additional","affiliation":[{"name":"Department of Neurology, University of Texas Medical Branch, Galveston, TX 77555, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Seiko","family":"Ikezu","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Experimental Therapeutics, Boston University School of Medicine, Boston, MA 02118, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jennifer I","family":"Luebke","sequence":"additional","affiliation":[{"name":"Department of Anatomy and Neurobiology, Boston University School of Medicine, Boston, MA 02118, USA"},{"name":"Center for Systems Neuroscience, Boston University, Boston, MA 02118, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3979-8596","authenticated-orcid":false,"given":"Tsuneya","family":"Ikezu","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Experimental Therapeutics, Boston University School of Medicine, Boston, MA 02118, USA"},{"name":"Center for Systems Neuroscience, Boston University, Boston, MA 02118, USA"},{"name":"Department of Neurology and Alzheimer\u2019s Disease Center, Boston University School of Medicine, Boston, MA 02118, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2020,11,27]]},"reference":[{"key":"2021032318364247400_awaa376-B1","doi-asserted-by":"crossref","first-page":"72","DOI":"10.1038\/s41593-017-0022-z","article-title":"Reducing the RNA binding protein TIA1 protects against tau-mediated neurodegeneration in vivo","volume":"21","author":"Apicco","year":"2018","journal-title":"Nat Neurosci"},{"key":"2021032318364247400_awaa376-B2","doi-asserted-by":"crossref","first-page":"125","DOI":"10.1016\/S0197-4580(98)00018-9","article-title":"Cerebrospinal fluid tau protein as a potential diagnostic marker in Alzheimer's disease","volume":"19","author":"Arai","year":"1998","journal-title":"Neurobiol Aging"},{"key":"2021032318364247400_awaa376-B3","doi-asserted-by":"crossref","first-page":"631","DOI":"10.1212\/WNL.42.3.631","article-title":"Neurofibrillary tangles but not senile plaques parallel duration and severity of Alzheimer's disease","volume":"42","author":"Arriagada","year":"1992","journal-title":"Neurology"},{"key":"2021032318364247400_awaa376-B4","doi-asserted-by":"crossref","first-page":"1584","DOI":"10.1038\/nn.4132","article-title":"Depletion of microglia and inhibition of exosome synthesis halt tau propagation","volume":"18","author":"Asai","year":"2015","journal-title":"Nat Neurosci"},{"key":"2021032318364247400_awaa376-B5","doi-asserted-by":"crossref","first-page":"1207","DOI":"10.3233\/JAD-160371","article-title":"Extracellular vesicles containing P301L mutant tau accelerate pathological tau phosphorylation and oligomer formation but do not seed mature neurofibrillary tangles in ALZ17 mice","volume":"54","author":"Baker","year":"2016","journal-title":"J Alzheimers Dis"},{"key":"2021032318364247400_awaa376-B6","doi-asserted-by":"crossref","first-page":"709","DOI":"10.1001\/archneur.1982.00510230035010","article-title":"Decreased Csf concentrations of homovanillic-acid and gamma-aminobutyric acid in Alzheimers-disease\u2014age-related or disease-related modifications","volume":"39","author":"Bareggi","year":"1982","journal-title":"Arch Neurol"},{"key":"2021032318364247400_awaa376-B7","doi-asserted-by":"crossref","first-page":"696","DOI":"10.1182\/blood-2009-07-231449","article-title":"Galectin-5 is bound onto the surface of rat reticulocyte exosomes and modulates vesicle uptake by macrophages","volume":"115","author":"Barres","year":"2010","journal-title":"Blood"},{"key":"2021032318364247400_awaa376-B8","doi-asserted-by":"crossref","first-page":"751","DOI":"10.1016\/j.bbrc.2018.03.209","article-title":"Suppression of tau propagation using an inhibitor that targets the DK-switch of nSMase2","volume":"499","author":"Bilousova","year":"2018","journal-title":"Biochem Biophys Res Commun"},{"key":"2021032318364247400_awaa376-B9","doi-asserted-by":"crossref","first-page":"239","DOI":"10.1007\/BF00308809","article-title":"Neuropathological stageing of Alzheimer-related changes","volume":"82","author":"Braak","year":"1991","journal-title":"Acta Neuropathol"},{"key":"2021032318364247400_awaa376-B10","doi-asserted-by":"crossref","first-page":"1721","DOI":"10.1007\/s00018-019-03349-1","article-title":"Mechanisms of secretion and spreading of pathological tau protein","volume":"77","author":"Brunello","year":"2020","journal-title":"Cell Mol Life Sci"},{"key":"2021032318364247400_awaa376-B11","doi-asserted-by":"crossref","first-page":"160","DOI":"10.1038\/nrn.2015.29","article-title":"Extracellular vesicles round off communication in the nervous system","volume":"17","author":"Budnik","year":"2016","journal-title":"Nat Rev Neurosci"},{"key":"2021032318364247400_awaa376-B12","doi-asserted-by":"crossref","first-page":"3662","DOI":"10.1073\/pnas.0307231101","article-title":"Tonic inhibition in mouse hippocampal CA1 pyramidal neurons is mediated by alpha5 subunit-containing gamma-aminobutyric acid type A receptors","volume":"101","author":"Caraiscos","year":"2004","journal-title":"Proc Natl Acad Sci USA"},{"key":"2021032318364247400_awaa376-B13","doi-asserted-by":"crossref","first-page":"201","DOI":"10.1002\/cne.902600205","article-title":"Somatostatin immunoreactive neurons in the human hippocampus and cortex shown by immunogold\/silver intensification on vibratome sections: coexistence with neuropeptide Y neurons, and effects in Alzheimer-type dementia","volume":"260","author":"Chan-Palay","year":"1987","journal-title":"J Comp Neurol"},{"key":"2021032318364247400_awaa376-B14","doi-asserted-by":"crossref","first-page":"1188","DOI":"10.1038\/mp.2014.127","article-title":"Prognostic serum miRNA biomarkers associated with Alzheimer's disease shows concordance with neuropsychological and neuroimaging assessment","volume":"20","author":"Cheng","year":"2015","journal-title":"Mol Psychiatry"},{"key":"2021032318364247400_awaa376-B15","doi-asserted-by":"crossref","first-page":"17380","DOI":"10.1073\/pnas.1304266110","article-title":"Cancer cell exosomes depend on cell-surface heparan sulfate proteoglycans for their internalization and functional activity","volume":"110","author":"Christianson","year":"2013","journal-title":"Proc Natl Acad Sci USA"},{"key":"2021032318364247400_awaa376-B16","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1007\/s00401-019-02087-9","article-title":"From the prion-like propagation hypothesis to therapeutic strategies of anti-tau immunotherapy","volume":"139","author":"Colin","year":"2020","journal-title":"Acta Neuropathol"},{"key":"2021032318364247400_awaa376-B17","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1016\/bs.mcb.2017.06.005","article-title":"Production of recombinant tau oligomers in vitro","volume":"141","author":"Combs","year":"2017","journal-title":"Methods Cell Biol"},{"key":"2021032318364247400_awaa376-B18","doi-asserted-by":"crossref","first-page":"36338","DOI":"10.1038\/srep36338","article-title":"Detailed analysis of protein topology of extracellular vesicles-evidence of unconventional membrane protein orientation","volume":"6","author":"Cvjetkovic","year":"2016","journal-title":"Sci Rep"},{"key":"2021032318364247400_awaa376-B19","doi-asserted-by":"crossref","first-page":"42","DOI":"10.1186\/1750-1326-7-42","article-title":"Exosomal cell-to-cell transmission of alpha synuclein oligomers","volume":"7","author":"Danzer","year":"2012","journal-title":"Mol Neurodegener"},{"key":"2021032318364247400_awaa376-B20","doi-asserted-by":"crossref","first-page":"279","DOI":"10.1038\/288279a0","article-title":"Reduced somatostatin-like immunoreactivity in cerebral cortex from cases of Alzheimer disease and Alzheimer senile dementa","volume":"288","author":"Davies","year":"1980","journal-title":"Nature"},{"key":"2021032318364247400_awaa376-B21","doi-asserted-by":"crossref","first-page":"17789","DOI":"10.1074\/jbc.M600544200","article-title":"Composition of perineuronal net extracellular matrix in rat brain: a different disaccharide composition for the net-associated proteoglycans","volume":"281","author":"Deepa","year":"2006","journal-title":"J Biol Chem"},{"key":"2021032318364247400_awaa376-B22","doi-asserted-by":"crossref","first-page":"292","DOI":"10.1007\/s11481-017-9768-z","article-title":"Extracellular vesicle biology in Alzheimer's disease and related tauopathy","volume":"13","author":"DeLeo","year":"2018","journal-title":"J Neuroimmune Pharmacol"},{"key":"2021032318364247400_awaa376-B23","doi-asserted-by":"crossref","first-page":"361","DOI":"10.1016\/j.tins.2019.02.007","article-title":"Neuroimmune crosstalk through extracellular vesicles in health and disease","volume":"42","author":"Delpech","year":"2019","journal-title":"Trends Neurosci"},{"key":"2021032318364247400_awaa376-B24","doi-asserted-by":"crossref","first-page":"e100760","DOI":"10.1371\/journal.pone.0100760","article-title":"Ectosomes: a new mechanism for non-exosomal secretion of tau protein","volume":"9","author":"Dujardin","year":"2014","journal-title":"PLoS One"},{"key":"2021032318364247400_awaa376-B25","doi-asserted-by":"crossref","first-page":"3612","DOI":"10.1016\/j.celrep.2018.03.021","article-title":"Extracellular monomeric and aggregated tau efficiently enter human neurons through overlapping but distinct pathways","volume":"22","author":"Evans","year":"2018","journal-title":"Cell Rep"},{"key":"2021032318364247400_awaa376-B26","doi-asserted-by":"crossref","first-page":"137","DOI":"10.1038\/s41586-018-0454-y","article-title":"Structures of filaments from Pick's disease reveal a novel tau protein fold","volume":"561","author":"Falcon","year":"2018","journal-title":"Nature"},{"key":"2021032318364247400_awaa376-B27","doi-asserted-by":"crossref","first-page":"420","DOI":"10.1038\/s41586-019-1026-5","article-title":"Novel tau filament fold in chronic traumatic encephalopathy encloses hydrophobic molecules","volume":"568","author":"Falcon","year":"2019","journal-title":"Nature"},{"key":"2021032318364247400_awaa376-B28","doi-asserted-by":"crossref","first-page":"9683","DOI":"10.1073\/pnas.0308413101","article-title":"Cells release prions in association with exosomes","volume":"101","author":"Fevrier","year":"2004","journal-title":"Proc Natl Acad Sci USA"},{"key":"2021032318364247400_awaa376-B29","doi-asserted-by":"crossref","first-page":"600","DOI":"10.1016\/j.jalz.2014.06.008","article-title":"Identification of preclinical Alzheimer's disease by a profile of pathogenic proteins in neurally derived blood exosomes: a case-control study","volume":"11","author":"Fiandaca","year":"2015","journal-title":"Alzheimers Dementia"},{"key":"2021032318364247400_awaa376-B30","doi-asserted-by":"crossref","first-page":"185","DOI":"10.1038\/nature23002","article-title":"Cryo-EM structures of tau filaments from Alzheimer's disease","volume":"547","author":"Fitzpatrick","year":"2017","journal-title":"Nature"},{"key":"2021032318364247400_awaa376-B31","doi-asserted-by":"crossref","first-page":"1901","DOI":"10.1002\/pro.3499","article-title":"Soluble tau aggregates, not large fibrils, are the toxic species that display seeding and cross-seeding behavior","volume":"27","author":"Ghag","year":"2018","journal-title":"Protein Sci"},{"key":"2021032318364247400_awaa376-B32","doi-asserted-by":"crossref","first-page":"1813","DOI":"10.3390\/ijms18081813","article-title":"Towards a better understanding of GABAergic remodeling in Alzheimer's disease","volume":"18","author":"Govindpani","year":"2017","journal-title":"Int J Mol Sci"},{"key":"2021032318364247400_awaa376-B33","doi-asserted-by":"crossref","first-page":"257","DOI":"10.1016\/j.nbd.2015.02.009","article-title":"From molecule to molecule and cell to cell: prion-like mechanisms in amyotrophic lateral sclerosis","volume":"77","author":"Grad","year":"2015","journal-title":"Neurobiol Dis"},{"key":"2021032318364247400_awaa376-B34","doi-asserted-by":"crossref","first-page":"2635","DOI":"10.1084\/jem.20160833","article-title":"Unique pathological tau conformers from Alzheimer's brains transmit tau pathology in nontransgenic mice","volume":"213","author":"Guo","year":"2016","journal-title":"J Exp Med"},{"key":"2021032318364247400_awaa376-B35","doi-asserted-by":"crossref","first-page":"717","DOI":"10.1007\/s00401-017-1674-1","article-title":"Hyperphosphorylated tau causes reduced hippocampal CA1 excitability by relocating the axon initial segment","volume":"133","author":"Hatch","year":"2017","journal-title":"Acta Neuropathol"},{"key":"2021032318364247400_awaa376-B36","doi-asserted-by":"crossref","first-page":"3346","DOI":"10.1074\/jbc.M406680200","article-title":"Tetraspanin CD82 attenuates cellular morphogenesis through down-regulating integrin alpha 6-mediated cell adhesion","volume":"280","author":"He","year":"2005","journal-title":"J Biol Chem"},{"key":"2021032318364247400_awaa376-B37","doi-asserted-by":"crossref","first-page":"E4376","DOI":"10.1073\/pnas.1411649111","article-title":"Proteopathic tau seeding predicts tauopathy in vivo","volume":"111","author":"Holmes","year":"2014","journal-title":"Proc Natl Acad Sci USA"},{"key":"2021032318364247400_awaa376-B38","doi-asserted-by":"crossref","first-page":"329","DOI":"10.1038\/nature15756","article-title":"Tumour exosome integrins determine organotropic metastasis","volume":"527","author":"Hoshino","year":"2015","journal-title":"Nature"},{"key":"2021032318364247400_awaa376-B39","doi-asserted-by":"crossref","first-page":"1066","DOI":"10.1016\/j.jalz.2016.01.014","article-title":"Hyperphosphorylation determines both the spread and the morphology of tau pathology","volume":"12","author":"Hu","year":"2016","journal-title":"Alzheimers Dement"},{"key":"2021032318364247400_awaa376-B40","doi-asserted-by":"crossref","first-page":"490","DOI":"10.1038\/nbt.2886","article-title":"Label-free detection and molecular profiling of exosomes with a nano-plasmonic sensor","volume":"32","author":"Im","year":"2014","journal-title":"Nat Biotechnol"},{"key":"2021032318364247400_awaa376-B41","doi-asserted-by":"crossref","first-page":"259","DOI":"10.1007\/s00401-018-1937-5","article-title":"TIA1 regulates the generation and response to toxic tau oligomers","volume":"137","author":"Jiang","year":"2019","journal-title":"Acta Neuropathol"},{"key":"2021032318364247400_awaa376-B42","doi-asserted-by":"crossref","first-page":"1276","DOI":"10.1016\/j.cell.2017.05.018","article-title":"A unique microglia type associated with restricting development of Alzheimer's disease","volume":"169","author":"Keren-Shaul","year":"2017","journal-title":"Cell"},{"key":"2021032318364247400_awaa376-B43","doi-asserted-by":"crossref","first-page":"575","DOI":"10.1016\/j.trci.2018.06.014","article-title":"Inflammation as a central mechanism in Alzheimer's disease","volume":"4","author":"Kinney","year":"2018","journal-title":"Alzheimers Dement (N Y)"},{"key":"2021032318364247400_awaa376-B44","doi-asserted-by":"crossref","first-page":"566","DOI":"10.1016\/j.immuni.2017.08.008","article-title":"The TREM2-APOE pathway drives the transcriptional phenotype of dysfunctional microglia in neurodegenerative diseases","volume":"47","author":"Krasemann","year":"2017","journal-title":"Immunity"},{"key":"2021032318364247400_awaa376-B45","doi-asserted-by":"crossref","first-page":"1094","DOI":"10.1038\/ng.439","article-title":"Genome-wide association study identifies variants at CLU and CR1 associated with Alzheimer's disease","volume":"41","author":"Lambert","year":"2009","journal-title":"Nat Genet"},{"key":"2021032318364247400_awaa376-B46","doi-asserted-by":"crossref","first-page":"34","DOI":"10.1186\/2051-5960-1-34","article-title":"Tau pathology induces loss of GABAergic interneurons leading to altered synaptic plasticity and behavioral impairments","volume":"1","author":"Levenga","year":"2013","journal-title":"Acta Neuropathol Commun"},{"key":"2021032318364247400_awaa376-B47","doi-asserted-by":"crossref","first-page":"332","DOI":"10.1038\/s41586-019-1195-2","article-title":"Single-cell transcriptomic analysis of Alzheimer's disease","volume":"570","author":"Mathys","year":"2019","journal-title":"Nature"},{"key":"2021032318364247400_awaa376-B48","doi-asserted-by":"crossref","first-page":"e0220125","DOI":"10.1371\/journal.pone.0220125","article-title":"Cell-autonomous and non-cell autonomous effects of neuronal BIN1 loss in vivo","volume":"14","author":"McAvoy","year":"2019","journal-title":"PLoS One"},{"key":"2021032318364247400_awaa376-B49","doi-asserted-by":"crossref","first-page":"14893","DOI":"10.1074\/jbc.M115.652693","article-title":"Tau trimers are the minimal propagation unit spontaneously internalized to seed intracellular aggregation","volume":"290","author":"Mirbaha","year":"2015","journal-title":"J Biol Chem"},{"key":"2021032318364247400_awaa376-B50","doi-asserted-by":"crossref","first-page":"3257","DOI":"10.1182\/blood-2004-03-0824","article-title":"Endocytosis, intracellular sorting, and processing of exosomes by dendritic cells","volume":"104","author":"Morelli","year":"2004","journal-title":"Blood"},{"key":"2021032318364247400_awaa376-B51","doi-asserted-by":"crossref","first-page":"24641","DOI":"10.3402\/jev.v3.24641","article-title":"Routes and mechanisms of extracellular vesicle uptake","volume":"3","author":"Mulcahy","year":"2014","journal-title":"J Extracell Vesicles"},{"key":"2021032318364247400_awaa376-B52","doi-asserted-by":"crossref","first-page":"896","DOI":"10.1002\/alz.12089","article-title":"Proteomic and biological profiling of extracellular vesicles from Alzheimer's disease human brain tissues","volume":"16","author":"Muraoka","year":"2020","journal-title":"Alzheimers Dement"},{"key":"2021032318364247400_awaa376-B53","doi-asserted-by":"crossref","first-page":"1059","DOI":"10.3389\/fnins.2019.01059","article-title":"Proteomic profiling of extracellular vesicles isolated from cerebrospinal fluid of former national football league players at risk for chronic traumatic encephalopathy","volume":"13","author":"Muraoka","year":"2019","journal-title":"Front Neurosci"},{"key":"2021032318364247400_awaa376-B54","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1016\/j.ymeth.2020.02.002","article-title":"Assessment of separation methods for extracellular vesicles from human and mouse brain tissues and human cerebrospinal fluids","volume":"177","author":"Muraoka","year":"2020","journal-title":"Methods"},{"key":"2021032318364247400_awaa376-B55","doi-asserted-by":"crossref","first-page":"11406","DOI":"10.1523\/JNEUROSCI.1230-17.2017","article-title":"Pathological tau strains from human brains recapitulate the diversity of tauopathies in nontransgenic mouse brain","volume":"37","author":"Narasimhan","year":"2017","journal-title":"J Neurosci"},{"key":"2021032318364247400_awaa376-B56","doi-asserted-by":"crossref","first-page":"1668","DOI":"10.1158\/0008-5472.CAN-09-2470","article-title":"Cell surface tetraspanin tspan8 contributes to molecular pathways of exosome-induced endothelial cell activation","volume":"70","author":"Nazarenko","year":"2010","journal-title":"Cancer Res"},{"key":"2021032318364247400_awaa376-B57","doi-asserted-by":"crossref","first-page":"435","DOI":"10.1001\/archneurol.2009.15","article-title":"Epilepsy and cognitive impairments in Alzheimer disease","volume":"66","author":"Palop","year":"2009","journal-title":"Arch Neurol"},{"key":"2021032318364247400_awaa376-B58","doi-asserted-by":"crossref","first-page":"43108","DOI":"10.1074\/jbc.M112.404467","article-title":"The exosome secretory pathway transports amyloid precursor protein carboxyl-terminal fragments from the cell into the brain extracellular space","volume":"287","author":"Perez-Gonzalez","year":"2012","journal-title":"J Biol Chem"},{"key":"2021032318364247400_awaa376-B59","doi-asserted-by":"crossref","first-page":"12445","DOI":"10.1074\/jbc.M115.709485","article-title":"Extracellular vesicles isolated from the brains of rTg4510 mice seed tau protein aggregation in a threshold-dependent manner","volume":"291","author":"Polanco","year":"2016","journal-title":"J Biol Chem"},{"key":"2021032318364247400_awaa376-B60","doi-asserted-by":"crossref","first-page":"1652","DOI":"10.1074\/jbc.M115.686295","article-title":"Fibronectin on the surface of myeloma cell-derived exosomes mediates exosome-cell interactions","volume":"291","author":"Purushothaman","year":"2016","journal-title":"J Biol Chem"},{"key":"2021032318364247400_awaa376-B61","doi-asserted-by":"crossref","first-page":"1818","DOI":"10.1182\/blood-2010-12-326595","article-title":"CD81 is essential for the formation of membrane protrusions and regulates Rac1-activation in adhesion-dependent immune cell migration","volume":"118","author":"Quast","year":"2011","journal-title":"Blood"},{"key":"2021032318364247400_awaa376-B62","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1007\/978-981-32-9358-8_11","article-title":"Tau secretion","volume":"1184","author":"Ruan","year":"2019","journal-title":"Adv Exp Med Biol"},{"key":"2021032318364247400_awaa376-B63","doi-asserted-by":"crossref","first-page":"3842","DOI":"10.1074\/jbc.M111.277061","article-title":"Exosome-associated tau is secreted in tauopathy models and is selectively phosphorylated in cerebrospinal fluid in early Alzheimer disease","volume":"287","author":"Saman","year":"2012","journal-title":"J Biol Chem"},{"key":"2021032318364247400_awaa376-B64","doi-asserted-by":"crossref","first-page":"1566","DOI":"10.1111\/epi.13849","article-title":"A randomized, double-blind, placebo-controlled crossover study of the effects of levetiracetam on cognition, mood, and balance in healthy older adults","volume":"58","author":"Schoenberg","year":"2017","journal-title":"Epilepsia"},{"key":"2021032318364247400_awaa376-B65","doi-asserted-by":"crossref","first-page":"113","DOI":"10.1007\/978-1-4939-7816-8_9","article-title":"Preparation and characterization of tau oligomer strains","volume":"1779","author":"Sengupta","year":"2018","journal-title":"Methods Mol Biol"},{"key":"2021032318364247400_awaa376-B66","doi-asserted-by":"crossref","first-page":"855","DOI":"10.3233\/JAD-189010","article-title":"Tau immunotherapies for Alzheimer's disease and related tauopathies: progress and potential pitfalls","volume":"66","author":"Sigurdsson","year":"2018","journal-title":"J Alzheimers Dis"},{"key":"2021032318364247400_awaa376-B67","doi-asserted-by":"crossref","first-page":"40","DOI":"10.1016\/j.neurobiolaging.2016.09.006","article-title":"The GABAergic septohippocampal connection is impaired in a mouse model of tauopathy","volume":"49","author":"Soler","year":"2017","journal-title":"Neurobiol Aging"},{"key":"2021032318364247400_awaa376-B68","doi-asserted-by":"crossref","first-page":"1099","DOI":"10.3233\/JAD-151028","article-title":"Preliminary study of plasma exosomal tau as a potential biomarker for chronic traumatic encephalopathy","volume":"51","author":"Stern","year":"2016","journal-title":"J Alzheimers Dis"},{"key":"2021032318364247400_awaa376-B69","doi-asserted-by":"crossref","first-page":"7164","DOI":"10.1038\/ncomms8164","article-title":"Directional cell movement through tissues is controlled by exosome secretion","volume":"6","author":"Sung","year":"2015","journal-title":"Nat Commun"},{"key":"2021032318364247400_awaa376-B70","doi-asserted-by":"crossref","first-page":"213","DOI":"10.1038\/nrm.2017.125","article-title":"Shedding light on the cell biology of extracellular vesicles","volume":"19","author":"van Niel","year":"2018","journal-title":"Nat Rev Mol Cell Biol"},{"key":"2021032318364247400_awaa376-B71","doi-asserted-by":"crossref","first-page":"1579","DOI":"10.1111\/j.1528-1167.2011.03086.x","article-title":"Stereologic estimation of hippocampal GluR2\/3-and calretinin-immunoreactive hilar neurons (presumptive mossy cells) in two mouse models of temporal lobe epilepsy","volume":"52","author":"Volz","year":"2011","journal-title":"Epilepsia"},{"key":"2021032318364247400_awaa376-B72","doi-asserted-by":"crossref","first-page":"1158","DOI":"10.1001\/jamaneurol.2013.136","article-title":"Seizures and epileptiform activity in the early stages of Alzheimer disease","volume":"70","author":"Vossel","year":"2013","journal-title":"Jama Neurol"},{"key":"2021032318364247400_awaa376-B73","doi-asserted-by":"crossref","first-page":"541","DOI":"10.3233\/JAD-180776","article-title":"Neuronal exosome-derived human tau is toxic to recipient mouse neurons in vivo","volume":"67","author":"Winston","year":"2019","journal-title":"J Alzheimers Dis"},{"key":"2021032318364247400_awaa376-B74","doi-asserted-by":"crossref","first-page":"63","DOI":"10.1016\/j.dadm.2016.04.001","article-title":"Prediction of conversion from mild cognitive impairment to dementia with neuronally derived blood exosome protein profile","volume":"3","author":"Winston","year":"2016","journal-title":"Alzheimers Dement (Amst)"},{"key":"2021032318364247400_awaa376-B75","doi-asserted-by":"crossref","first-page":"387","DOI":"10.1084\/jem.20131685","article-title":"Neuronal activity regulates extracellular tau in vivo","volume":"211","author":"Yamada","year":"2014","journal-title":"J Exp Med"},{"key":"2021032318364247400_awaa376-B76","doi-asserted-by":"crossref","first-page":"1706801","DOI":"10.1080\/20013078.2019.1706801","article-title":"Activated human astrocyte-derived extracellular vesicles modulate neuronal uptake, differentiation and firing","volume":"9","author":"You","year":"2020","journal-title":"J Extracell Vesicles"},{"key":"2021032318364247400_awaa376-B77","doi-asserted-by":"crossref","first-page":"104512","DOI":"10.1016\/j.nbd.2019.104512","article-title":"Emerging roles of extracellular vesicles in neurodegenerative disorders","volume":"130","author":"You","year":"2019","journal-title":"Neurobiol Dis"},{"key":"2021032318364247400_awaa376-B78","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1186\/alzrt163","article-title":"Plasma tau levels in Alzheimer's disease","volume":"5","author":"Zetterberg","year":"2013","journal-title":"Alzheimers Res Ther"},{"key":"2021032318364247400_awaa376-B79","doi-asserted-by":"crossref","first-page":"283","DOI":"10.1038\/s41586-020-2043-0","article-title":"Novel tau filament fold in corticobasal degeneration","volume":"580","author":"Zhang","year":"2020","journal-title":"Nature"},{"key":"2021032318364247400_awaa376-B80","doi-asserted-by":"crossref","first-page":"602","DOI":"10.1001\/archneur.1984.04210080010005","article-title":"Gamma-aminobutyric acid and homovanillic-acid concentration in the Csf of patients with senile dementia of Alzheimers type","volume":"41","author":"Zimmer","year":"1984","journal-title":"Arch Neurol"}],"container-title":["Brain"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/academic.oup.com\/brain\/article-pdf\/144\/1\/288\/36677094\/awaa376.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"http:\/\/academic.oup.com\/brain\/article-pdf\/144\/1\/288\/36677094\/awaa376.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,3,23]],"date-time":"2021-03-23T14:37:40Z","timestamp":1616510260000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/brain\/article\/144\/1\/288\/6007752"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,11,27]]},"references-count":80,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2020,11,27]]},"published-print":{"date-parts":[[2021,2,12]]}},"URL":"https:\/\/doi.org\/10.1093\/brain\/awaa376","relation":{"has-preprint":[{"id-type":"doi","id":"10.1101\/2020.03.15.992719","asserted-by":"object"}]},"ISSN":["0006-8950","1460-2156"],"issn-type":[{"value":"0006-8950","type":"print"},{"value":"1460-2156","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2021,1,1]]},"published":{"date-parts":[[2020,11,27]]}}}