{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,12]],"date-time":"2026-10-12T02:58:09Z","timestamp":1791773889316,"version":"4.3.4"},"reference-count":34,"publisher":"National Academy of Sciences","issue":"1","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2014,1,7]]},"abstract":"<jats:title>Significance<\/jats:title>\n                  <jats:p>Alzheimer's disease is pathologically characterized by extracellular amyloid-\u03b2 plaques and intracellular neurofibrillary tangles (NFTs). It has long been assumed that the accumulation of tau into NFTs causes neuronal dysfunction and death, and is a proximate cause of dementia in patients with Alzheimer\u2019s disease. This assumption underlies the NFT-busting drugs currently in clinical trials and research efforts aimed at understanding tau aggregation. Our study tested the dogma that NFT-bearing neurons are indeed impaired in their ability to respond to complex sensory stimuli. Using two-photon imaging in awake mice with NFT pathology, we found that individual neurons with NFTs respond to visual stimuli and do not impair local circuits. These unexpected results suggest that the presence of an NFT does not inevitably lead to gross physiological alterations.<\/jats:p>","DOI":"10.1073\/pnas.1318807111","type":"journal-article","created":{"date-parts":[[2013,12,24]],"date-time":"2013-12-24T21:50:31Z","timestamp":1387921831000},"page":"510-514","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":191,"title":["Neurofibrillary tangle-bearing neurons are functionally integrated in cortical circuits in vivo"],"prefix":"10.1073","volume":"111","author":[{"given":"Kishore V.","family":"Kuchibhotla","sequence":"first","affiliation":[{"name":"Alzheimer\u2019s Disease Research Laboratory, Department of Neurology, MassGeneral Institute for Neurodegenerative Disease, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA 02129;"},{"name":"Skirball Institute, NYU School of Medicine, New York, NY 10016;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susanne","family":"Wegmann","sequence":"additional","affiliation":[{"name":"Alzheimer\u2019s Disease Research Laboratory, Department of Neurology, MassGeneral Institute for Neurodegenerative Disease, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA 02129;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katherine J.","family":"Kopeikina","sequence":"additional","affiliation":[{"name":"Alzheimer\u2019s Disease Research Laboratory, Department of Neurology, MassGeneral Institute for Neurodegenerative Disease, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA 02129;"},{"name":"Department of Anatomy and Neurobiology, Boston University School of Medicine, Boston, MA 02118;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jonathan","family":"Hawkes","sequence":"additional","affiliation":[{"name":"Alzheimer\u2019s Disease Research Laboratory, Department of Neurology, MassGeneral Institute for Neurodegenerative Disease, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA 02129;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nikita","family":"Rudinskiy","sequence":"additional","affiliation":[{"name":"Alzheimer\u2019s Disease Research Laboratory, Department of Neurology, MassGeneral Institute for Neurodegenerative Disease, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA 02129;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark L.","family":"Andermann","sequence":"additional","affiliation":[{"name":"Division of Endocrinology, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tara L.","family":"Spires-Jones","sequence":"additional","affiliation":[{"name":"Alzheimer\u2019s Disease Research Laboratory, Department of Neurology, MassGeneral Institute for Neurodegenerative Disease, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA 02129;"},{"name":"Centre for Cognitive and Neural Systems, University of Edinburgh Neuroscience, Edinburgh EH8 9JZ, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brian J.","family":"Bacskai","sequence":"additional","affiliation":[{"name":"Alzheimer\u2019s Disease Research Laboratory, Department of Neurology, MassGeneral Institute for Neurodegenerative Disease, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA 02129;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bradley T.","family":"Hyman","sequence":"additional","affiliation":[{"name":"Alzheimer\u2019s Disease Research Laboratory, Department of Neurology, MassGeneral Institute for Neurodegenerative Disease, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA 02129;"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2013,12,24]]},"reference":[{"key":"e_1_3_3_1_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(17)38495-8"},{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1038\/1565"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1007\/BF00308809"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1749-6632.2000.tb06906.x"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.tins.2008.11.007"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1038\/emboj.2011.376"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1002\/anie.200802621"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.neurobiolaging.2010.12.012"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00401-012-1038-9"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1113694"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1006\/exnr.2002.8014"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1186\/1750-1326-8-9"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.expneurol.2009.07.029"},{"key":"e_1_3_3_14_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2011.11.013"},{"key":"e_1_3_3_15_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2008.06.008"},{"key":"e_1_3_3_16_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0400417101"},{"key":"e_1_3_3_17_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2010.08.002"},{"key":"e_1_3_3_18_2","doi-asserted-by":"publisher","DOI":"10.1038\/nn.2876"},{"key":"e_1_3_3_19_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.nbd.2012.01.012"},{"key":"e_1_3_3_20_2","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms1783"},{"key":"e_1_3_3_21_2","doi-asserted-by":"publisher","DOI":"10.1017\/S1431927611000535"},{"key":"e_1_3_3_22_2","doi-asserted-by":"publisher","DOI":"10.1093\/jnen\/61.9.797"},{"key":"e_1_3_3_23_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0053547"},{"key":"e_1_3_3_24_2","doi-asserted-by":"publisher","DOI":"10.1385\/NMM:2:2:131"},{"key":"e_1_3_3_25_2","doi-asserted-by":"publisher","DOI":"10.2353\/ajpath.2006.050840"},{"key":"e_1_3_3_26_2","doi-asserted-by":"publisher","DOI":"10.1097\/NEN.0b013e318220a658"},{"key":"e_1_3_3_27_2","doi-asserted-by":"publisher","DOI":"10.3389\/fneur.2013.00114"},{"key":"e_1_3_3_28_2","doi-asserted-by":"publisher","DOI":"10.1007\/s12031-011-9566-7"},{"key":"e_1_3_3_29_2","doi-asserted-by":"publisher","DOI":"10.2478\/s13380-012-0032-y"},{"key":"e_1_3_3_30_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(13)70090-5"},{"key":"e_1_3_3_31_2","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.0587-07.2007"},{"key":"e_1_3_3_32_2","doi-asserted-by":"publisher","DOI":"10.1186\/1750-1326-6-39"},{"key":"e_1_3_3_33_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature08890"},{"key":"e_1_3_3_34_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2011.11.013"}],"container-title":["Proceedings of the National Academy of Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/pnas.org\/doi\/pdf\/10.1073\/pnas.1318807111","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,4,12]],"date-time":"2022-04-12T23:23:12Z","timestamp":1649805792000},"score":1,"resource":{"primary":{"URL":"https:\/\/pnas.org\/doi\/full\/10.1073\/pnas.1318807111"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2013,12,24]]},"references-count":34,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2014,1,7]]}},"alternative-id":["10.1073\/pnas.1318807111"],"URL":"https:\/\/doi.org\/10.1073\/pnas.1318807111","relation":{"has-review":[{"id-type":"doi","id":"10.3410\/f.718218055.793489097","asserted-by":"object"}]},"ISSN":["0027-8424","1091-6490"],"issn-type":[{"value":"0027-8424","type":"print"},{"value":"1091-6490","type":"electronic"}],"subject":[],"published":{"date-parts":[[2013,12,24]]},"assertion":[{"value":"2013-12-24","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}