{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T17:28:38Z","timestamp":1792171718762,"version":"4.4.0"},"reference-count":60,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2017,3,31]],"date-time":"2017-03-31T00:00:00Z","timestamp":1490918400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01AG040311"],"award-info":[{"award-number":["R01AG040311"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["K24AG053435"],"award-info":[{"award-number":["K24AG053435"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["P50AG023501"],"award-info":[{"award-number":["P50AG023501"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["P01AG019724"],"award-info":[{"award-number":["P01AG019724"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Neuropathology Appl Neurobio"],"published-print":{"date-parts":[[2017,8]]},"abstract":"\n Aims<\/jats:title>\n \n Hyperphosphorylated tau neuronal cytoplasmic inclusions (ht\u2010\n NCI<\/jats:styled-content>\n ) are the best protein correlate of clinical decline in Alzheimer's disease (\n AD<\/jats:styled-content>\n ). Qualitative evidence identifies ht\u2010\n NCI<\/jats:styled-content>\n accumulating in the isodendritic core before the entorhinal cortex. Here, we used unbiased stereology to quantify ht\u2010\n NCI<\/jats:styled-content>\n burden in the locus coeruleus (LC) and dorsal raphe nucleus (DRN), aiming to characterize the impact of\n AD<\/jats:styled-content>\n pathology in these nuclei with a focus on early stages.\n <\/jats:p>\n <\/jats:sec>\n \n Methods<\/jats:title>\n \n We utilized unbiased stereology in a sample of 48 well\u2010characterized subjects enriched for controls and early\n AD<\/jats:styled-content>\n stages. ht\u2010\n NCI<\/jats:styled-content>\n counts were estimated in 60\u2010\u03bcm\u2010thick sections immunostained for p\u2010tau throughout\n LC<\/jats:styled-content>\n and\n DRN<\/jats:styled-content>\n . Data were integrated with unbiased estimates of\n LC<\/jats:styled-content>\n and\n DRN<\/jats:styled-content>\n neuronal population for a subset of cases.\n <\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n In Braak stage 0, 7.9% and 2.6% of neurons in\n LC<\/jats:styled-content>\n and\n DRN<\/jats:styled-content>\n , respectively, harbour ht\u2010\n NCI<\/jats:styled-content>\n s. Although the number of ht\u2010\n NCI<\/jats:styled-content>\n + neurons significantly increased by about 1.9\u00d7 between Braak stages 0 to I in\n LC<\/jats:styled-content>\n (\n P<\/jats:italic>\n = 0.02), we failed to detect any significant difference between Braak stage I and\n II<\/jats:styled-content>\n . Also, the number of ht\u2010\n NCI<\/jats:styled-content>\n + neurons remained stable in\n DRN<\/jats:styled-content>\n between all stages 0 and\n II<\/jats:styled-content>\n . Finally, the differential susceptibility to tau inclusions among nuclear subdivisions was more notable in\n LC<\/jats:styled-content>\n than in\n DRN<\/jats:styled-content>\n .\n <\/jats:p>\n <\/jats:sec>\n \n Conclusions<\/jats:title>\n \n LC<\/jats:styled-content>\n and\n DRN<\/jats:styled-content>\n neurons exhibited ht\u2010\n NCI<\/jats:styled-content>\n during\n AD<\/jats:styled-content>\n precortical stages. The ht\u2010\n NCI<\/jats:styled-content>\n increases along\n AD<\/jats:styled-content>\n progression on both nuclei, but quantitative changes in\n LC<\/jats:styled-content>\n precede\n DRN<\/jats:styled-content>\n changes.\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1111\/nan.12387","type":"journal-article","created":{"date-parts":[[2017,1,24]],"date-time":"2017-01-24T11:49:42Z","timestamp":1485258582000},"page":"393-408","source":"Crossref","is-referenced-by-count":234,"title":["Quantifying the accretion of hyperphosphorylated tau in the locus coeruleus and dorsal raphe nucleus: the pathological building blocks of early Alzheimer's disease"],"prefix":"10.1111","volume":"43","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4334-9424","authenticated-orcid":false,"given":"A. 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