{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,28]],"date-time":"2026-10-28T12:23:01Z","timestamp":1793190181541,"version":"4.5.0"},"reference-count":46,"publisher":"Society for Neuroscience","issue":"45","license":[{"start":{"date-parts":[[2023,5,9]],"date-time":"2023-05-09T00:00:00Z","timestamp":1683590400000},"content-version":"vor","delay-in-days":221,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-sa\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000049","name":"HHS | NIH | National Institute on Aging","doi-asserted-by":"publisher","award":["P30AG013854"],"award-info":[{"award-number":["P30AG013854"]}],"id":[{"id":"10.13039\/100000049","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000049","name":"HHS | NIH | National Institute on Aging","doi-asserted-by":"publisher","award":["R01AG062566"],"award-info":[{"award-number":["R01AG062566"]}],"id":[{"id":"10.13039\/100000049","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000049","name":"HHS | NIH | National Institute on Aging","doi-asserted-by":"publisher","award":["R01AG067781"],"award-info":[{"award-number":["R01AG067781"]}],"id":[{"id":"10.13039\/100000049","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000049","name":"HHS | NIH | National Institute on Aging","doi-asserted-by":"publisher","award":["R01AG045571"],"award-info":[{"award-number":["R01AG045571"]}],"id":[{"id":"10.13039\/100000049","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000049","name":"HHS | NIH | National Institute on Aging","doi-asserted-by":"publisher","award":["U19AG073153"],"award-info":[{"award-number":["U19AG073153"]}],"id":[{"id":"10.13039\/100000049","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J. Neurosci."],"published-print":{"date-parts":[[2022,11,9]]},"abstract":"<jats:p>Average aging is associated with a gradual decline of memory capacity. SuperAgers are humans \u226580 years of age who show exceptional episodic memory at least as good as individuals 20\u201330 years their junior. This study investigated whether neuronal integrity in the entorhinal cortex (ERC), an area critical for memory and selectively vulnerable to neurofibrillary degeneration, differentiated SuperAgers from cognitively healthy younger individuals, cognitively average peers (\u201cNormal Elderly\u201d), and individuals with amnestic mild cognitive impairment. Postmortem sections of the ERC were stained with cresyl violet to visualize neurons and immunostained with mouse monoclonal antibody PHF-1 to visualize neurofibrillary tangles. The cross-sectional area (i.e., size) of layer II and layer III\/V ERC neurons were quantified. Two-thirds of total participants were female. Unbiased stereology was used to quantitate tangles in a subgroup of SuperAgers and Normal Elderly. Linear mixed-effect models were used to determine differences across groups. Quantitative measurements found that the soma size of layer II ERC neurons in postmortem brain specimens were significantly larger in SuperAgers compared with all groups (<jats:italic>p<\/jats:italic>&lt; 0.05)\u2014including younger individuals 20\u201330 years their junior (<jats:italic>p<\/jats:italic>&lt; 0.005). SuperAgers had significantly fewer stereologically quantified Alzheimer's disease-related neurofibrillary tangles in layer II ERC than Normal Elderly (<jats:italic>p<\/jats:italic>&lt; 0.05). This difference in tangle burden in layer II between SuperAgers and Normal Elderly suggests that tangle-bearing neurons may be prone to shrinkage during aging. The finding that SuperAgers show ERC layer II neurons that are substantially larger even compared with individuals 20\u201330 years younger is remarkable, suggesting that layer II ERC integrity is a biological substrate of exceptional memory in old age.<\/jats:p><jats:p><jats:bold>SIGNIFICANCE STATEMENT<\/jats:bold>Average aging is associated with a gradual decline of memory. Previous research shows that an area critical for memory, the entorhinal cortex (ERC), is susceptible to the early formation of Alzheimer's disease neuropathology, even during average (or typical) trajectories of aging. The Northwestern University SuperAging Research Program studies unique individuals known as SuperAgers, individuals \u226580 years old who show exceptional memory that is at least as good as individuals 20\u201330 years their junior. In this study, we show that SuperAgers harbor larger, healthier neurons in the ERC compared with their cognitively average same-aged peers, those with amnestic mild cognitive impairment, and \u2013 remarkably \u2013 even compared with individuals 20\u201330 years younger. We conclude that larger ERC neurons are a biological signature of the SuperAging trajectory.<\/jats:p>","DOI":"10.1523\/jneurosci.0679-22.2022","type":"journal-article","created":{"date-parts":[[2022,9,30]],"date-time":"2022-09-30T17:45:10Z","timestamp":1664559910000},"page":"8587-8594","source":"Crossref","is-referenced-by-count":27,"title":["Integrity of Neuronal Size in the Entorhinal Cortex Is a Biological Substrate of Exceptional Cognitive Aging"],"prefix":"10.1523","volume":"42","author":[{"given":"Caren","family":"Nassif","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Allegra","family":"Kawles","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ivan","family":"Ayala","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Grace","family":"Minogue","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nathan P.","family":"Gill","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert A.","family":"Shepard","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonia","family":"Zouridakis","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rachel","family":"Keszycki","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hui","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qinwen","family":"Mao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Margaret E.","family":"Flanagan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eileen H.","family":"Bigio","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M.-Marsel","family":"Mesulam","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emily","family":"Rogalski","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9311-3295","authenticated-orcid":false,"given":"Changiz","family":"Geula","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tamar","family":"Gefen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"393","published-online":{"date-parts":[[2022,9,30]]},"reference":[{"key":"2023122005401121000_42.45.8587.1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jalz.2011.03.008"},{"key":"2023122005401121000_42.45.8587.2","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0b013e318266fc77"},{"key":"2023122005401121000_42.45.8587.3","doi-asserted-by":"publisher","DOI":"10.1007\/BF00690836"},{"key":"2023122005401121000_42.45.8587.4","first-page":"277","article-title":"Morphological changes in the human cerebral cortex in dementia","volume":"32","author":"Braak","year":"1991","journal-title":"J Hirnforsch"},{"key":"2023122005401121000_42.45.8587.5","doi-asserted-by":"publisher","DOI":"10.1007\/BF00308809"},{"key":"2023122005401121000_42.45.8587.6","doi-asserted-by":"publisher","DOI":"10.1159\/000116984"},{"key":"2023122005401121000_42.45.8587.7","doi-asserted-by":"publisher","DOI":"10.1155\/2008\/381243"},{"key":"2023122005401121000_42.45.8587.8","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1186\/s13195-020-00588-4","article-title":"The clinical promise of biomarkers of synapse damage or loss in Alzheimer's disease","volume":"12","author":"Colom-Cadena","year":"2020","journal-title":"Alzheimers Res Ther"},{"key":"2023122005401121000_42.45.8587.9","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2017.0627"},{"key":"2023122005401121000_42.45.8587.10","doi-asserted-by":"publisher","DOI":"10.1097\/NEN.0b013e31818fc72f"},{"key":"2023122005401121000_42.45.8587.11","doi-asserted-by":"publisher","DOI":"10.1111\/jgs.12967"},{"key":"2023122005401121000_42.45.8587.12","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.2998-14.2015"},{"key":"2023122005401121000_42.45.8587.13","doi-asserted-by":"publisher","DOI":"10.1016\/j.cortex.2017.10.015"},{"key":"2023122005401121000_42.45.8587.14","doi-asserted-by":"publisher","DOI":"10.3389\/fnagi.2019.00094"},{"key":"2023122005401121000_42.45.8587.15","doi-asserted-by":"publisher","DOI":"10.1093\/cercor\/bhaa409"},{"key":"2023122005401121000_42.45.8587.16","doi-asserted-by":"publisher","DOI":"10.1017\/S1355617712000847"},{"key":"2023122005401121000_42.45.8587.17","unstructured":"Heaton R , Miller S , Taylor M , Grant I (2004) Revised comprehensive norms for an expanded Halstead-Reitan battery: demographically adjusted neuropsychological norms for African American and caucasian adults. Lutz, FL: Psychological Assessment Resources."},{"key":"2023122005401121000_42.45.8587.18","doi-asserted-by":"publisher","DOI":"10.1016\/0197-4580(92)90111-A"},{"key":"2023122005401121000_42.45.8587.19","doi-asserted-by":"publisher","DOI":"10.1126\/science.6474172"},{"key":"2023122005401121000_42.45.8587.20","doi-asserted-by":"publisher","DOI":"10.1002\/ana.410200406"},{"key":"2023122005401121000_42.45.8587.21","doi-asserted-by":"publisher","DOI":"10.1080\/13854049608406689"},{"key":"2023122005401121000_42.45.8587.22","doi-asserted-by":"publisher","DOI":"10.1093\/cercor\/bhx047"},{"key":"2023122005401121000_42.45.8587.23","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0000000000001831"},{"key":"2023122005401121000_42.45.8587.24","doi-asserted-by":"publisher","DOI":"10.1097\/WCO.0000000000000910"},{"key":"2023122005401121000_42.45.8587.25","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0000000000004891"},{"key":"2023122005401121000_42.45.8587.26","doi-asserted-by":"publisher","DOI":"10.1080\/09658211.2014.985590"},{"key":"2023122005401121000_42.45.8587.27","doi-asserted-by":"publisher","DOI":"10.1093\/cercor\/7.8.722"},{"key":"2023122005401121000_42.45.8587.28","doi-asserted-by":"publisher","DOI":"10.1002\/1096-9861(20000703)422:3<396::AID-CNE6>3.0.CO;2-R"},{"key":"2023122005401121000_42.45.8587.29","doi-asserted-by":"publisher","DOI":"10.1002\/cne.23415"},{"key":"2023122005401121000_42.45.8587.30","doi-asserted-by":"publisher","DOI":"10.1002\/cne.902140206"},{"key":"2023122005401121000_42.45.8587.31","doi-asserted-by":"publisher","DOI":"10.1038\/nrn3200"},{"key":"2023122005401121000_42.45.8587.32","doi-asserted-by":"publisher","DOI":"10.1007\/s00401-022-02444-1"},{"key":"2023122005401121000_42.45.8587.33","doi-asserted-by":"publisher","DOI":"10.1162\/jocn_a_00300"},{"key":"2023122005401121000_42.45.8587.34","doi-asserted-by":"publisher","DOI":"10.1002\/hipo.22828"},{"key":"2023122005401121000_42.45.8587.35","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.med.47.1.387"},{"key":"2023122005401121000_42.45.8587.36","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.43.8.1467"},{"key":"2023122005401121000_42.45.8587.37","doi-asserted-by":"publisher","DOI":"10.1016\/j.neurobiolaging.2005.09.012"},{"key":"2023122005401121000_42.45.8587.38","unstructured":"Schmidt M (2004) Rey auditory verbal learning test: a handbook. Los Angeles: Western Psychological Services."},{"key":"2023122005401121000_42.45.8587.39","doi-asserted-by":"publisher","DOI":"10.1186\/alzrt94"},{"key":"2023122005401121000_42.45.8587.40","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.20-17-06587.2000"},{"key":"2023122005401121000_42.45.8587.41","doi-asserted-by":"publisher","DOI":"10.1016\/j.jneumeth.2007.03.019"},{"key":"2023122005401121000_42.45.8587.42","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.1492-16.2016"},{"key":"2023122005401121000_42.45.8587.43","doi-asserted-by":"publisher","DOI":"10.1016\/S0079-6123(08)61268-6"},{"key":"2023122005401121000_42.45.8587.44","doi-asserted-by":"publisher","DOI":"10.1093\/cercor\/3.5.465"},{"key":"2023122005401121000_42.45.8587.45","doi-asserted-by":"publisher","DOI":"10.1097\/WAD.0b013e318191c7dd"},{"key":"2023122005401121000_42.45.8587.46","doi-asserted-by":"publisher","DOI":"10.1016\/S0079-6123(07)63003-9"}],"container-title":["The Journal of Neuroscience"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1523\/JNEUROSCI.0679-22.2022","content-type":"unspecified","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1523\/JNEUROSCI.0679-22.2022","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,12,20]],"date-time":"2023-12-20T13:42:50Z","timestamp":1703079770000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.jneurosci.org\/lookup\/doi\/10.1523\/JNEUROSCI.0679-22.2022"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,9,30]]},"references-count":46,"journal-issue":{"issue":"45","published-online":{"date-parts":[[2022,11,9]]},"published-print":{"date-parts":[[2022,11,9]]}},"alternative-id":["10.1523\/JNEUROSCI.0679-22.2022"],"URL":"https:\/\/doi.org\/10.1523\/jneurosci.0679-22.2022","relation":{},"ISSN":["0270-6474","1529-2401"],"issn-type":[{"value":"0270-6474","type":"print"},{"value":"1529-2401","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,9,30]]}}}