{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,4]],"date-time":"2026-10-04T12:29:17Z","timestamp":1791116957588,"version":"4.1.0"},"reference-count":51,"publisher":"Oxford University Press (OUP)","issue":"8","license":[{"start":{"date-parts":[[2009,10,1]],"date-time":"2009-10-01T00:00:00Z","timestamp":1254355200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2009,10,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Following peripheral exposure, many transmissible spongiform encephalopathy (TSE) agents accumulate first in lymphoid tissues before spreading to the CNS (termed neuroinvasion) where they cause neurodegeneration. Early TSE agent accumulation upon follicular dendritic cells (FDCs) in lymphoid follicles appears critical for efficient neuroinvasion. Most clinical cases of variant Creutzfeldt-Jakob disease have occurred in young adults, although the reasons behind this apparent age-related susceptibility are uncertain. Host age has a significant influence on immune function. As FDC status and immune complex trapping is reduced in aged mice (600 days old), we hypothesized that this aging-related decline in FDC function might impair TSE pathogenesis. We show that coincident with the effects of host age on FDC status, the early TSE agent accumulation in the spleens of aged mice was significantly impaired. Furthermore, following peripheral exposure, none of the aged mice developed clinical TSE disease during their lifespans, although most mice displayed histopathological signs of TSE disease in their brains. Our data imply that the reduced status of FDCs in aged mice significantly impairs the early TSE agent accumulation in lymphoid tissues and subsequent neuroinvasion. Furthermore, the inefficient neuroinvasion in aged individuals may lead to significant levels of subclinical TSE disease in the population.<\/jats:p>","DOI":"10.4049\/jimmunol.0802695","type":"journal-article","created":{"date-parts":[[2009,9,28]],"date-time":"2009-09-28T20:48:50Z","timestamp":1254170930000},"page":"5199-5207","source":"Crossref","is-referenced-by-count":56,"title":["The Effects of Host Age on Follicular Dendritic Cell Status Dramatically Impair Scrapie Agent Neuroinvasion in Aged Mice"],"prefix":"10.1093","volume":"183","author":[{"given":"Karen L","family":"Brown","sequence":"first","affiliation":[{"name":"The Roslin Institute and Royal (Dick) School of Veterinary Sciences, University of Edinburgh , Roslin,","place":["United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gwennaelle J","family":"Wathne","sequence":"additional","affiliation":[{"name":"The Roslin Institute and Royal (Dick) School of Veterinary Sciences, University of Edinburgh , Roslin,","place":["United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jill","family":"Sales","sequence":"additional","affiliation":[{"name":"Biomathematics & Statistics Scotland , Edinburgh,","place":["United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Moira E","family":"Bruce","sequence":"additional","affiliation":[{"name":"The Roslin Institute and Royal (Dick) School of Veterinary Sciences, University of Edinburgh , Roslin,","place":["United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Neil A","family":"Mabbott","sequence":"additional","affiliation":[{"name":"The Roslin Institute and Royal (Dick) School of Veterinary Sciences, University of Edinburgh , Roslin,","place":["United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2009,10,15]]},"reference":[{"key":"2026012811282781700_R1","first-page":"1309","article-title":"Identification of a protein that purifies with the scrapie prion.","volume-title":"Science","year":"1982"},{"key":"2026012811282781700_R2","first-page":"6845","article-title":"Follicular dendritic cell dedifferentiation by treatment with an inhibitor of the lymphotoxin pathway dramatically reduces scrapie susceptibility.","volume-title":"J. 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