{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,4]],"date-time":"2026-05-04T22:14:43Z","timestamp":1777932883138,"version":"3.51.4"},"reference-count":38,"publisher":"SAGE Publications","issue":"4","license":[{"start":{"date-parts":[[2012,8,1]],"date-time":"2012-08-01T00:00:00Z","timestamp":1343779200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Rejuvenation Research"],"published-print":{"date-parts":[[2012,8]]},"abstract":"<jats:sec>\n                    <jats:title>Introduction:<\/jats:title>\n                    <jats:p>\n                      Circulating inflammatory markers may play an important role in cognitive impairment at older ages. Mice deficient for the chemokine (C-C motif) receptor 2 (\n                      <jats:italic toggle=\"yes\">CCR2<\/jats:italic>\n                      ) develop an accelerated Alzheimer-like pathology.\n                      <jats:italic toggle=\"yes\">CCR2<\/jats:italic>\n                      is also important in neurogenesis. To identify human gene transcripts most closely associated with Mini-Mental State Examination (MMSE) scores, we undertook a genome-wide and inflammation specific transcriptome screen in circulating leukocytes from a population-based sample.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods:<\/jats:title>\n                    <jats:p>\n                      We measured\n                      <jats:italic toggle=\"yes\">in vivo<\/jats:italic>\n                      transcript levels by microarray analysis in 691 subjects (mean age 72.6 years) in the InCHIANTI study (Invecchiare in Chianti, aging in the Chianti area). We assessed expression associations with MMSE performance at RNA collection and prior 9-year change in MMSE score in linear regression models.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results:<\/jats:title>\n                    <jats:p>\n                      In genome-wide analysis, raised\n                      <jats:italic toggle=\"yes\">CCR2<\/jats:italic>\n                      expression was cross-sectionally the most strongly associated transcript with lower MMSE score (beta=\u22120.16,\n                      <jats:italic toggle=\"yes\">p<\/jats:italic>\n                      =5.1\u00d710\n                      <jats:sup>\u22126<\/jats:sup>\n                      , false discovery rate (FDR;\n                      <jats:italic toggle=\"yes\">q<\/jats:italic>\n                      =0.077). Amongst inflammatory transcripts, only\n                      <jats:italic toggle=\"yes\">CCR2<\/jats:italic>\n                      expression was associated with both MMSE score and accelerated decline in score over the preceding 9 years (beta=\u22120.16,\n                      <jats:italic toggle=\"yes\">p<\/jats:italic>\n                      =5.1\u00d710\n                      <jats:sup>\u22126<\/jats:sup>\n                      ,\n                      <jats:italic toggle=\"yes\">q<\/jats:italic>\n                      =0.003; and beta=\u22120.13,\n                      <jats:italic toggle=\"yes\">p<\/jats:italic>\n                      =5.5\u00d710\n                      <jats:sup>\u22125<\/jats:sup>\n                      ,\n                      <jats:italic toggle=\"yes\">q<\/jats:italic>\n                      =0.03, respectively).\n                      <jats:italic toggle=\"yes\">CCR2<\/jats:italic>\n                      expression was also positively associated with apolipoprotein E (ApoE) e4 Alzheimer disease risk haplotype.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions:<\/jats:title>\n                    <jats:p>\n                      We show for the first time that\n                      <jats:italic toggle=\"yes\">CCR2<\/jats:italic>\n                      expression is associated with lower MMSE scores in an older human population. Laboratory models of\n                      <jats:italic toggle=\"yes\">Ccr2<\/jats:italic>\n                      -mediated \u03b2-amyloid removal and regulation of neurogenesis affecting cognitive function may be applicable in humans.\n                      <jats:italic toggle=\"yes\">CCR2<\/jats:italic>\n                      -mediated pathways may provide a possible focus for intervention to potentiate protective reactions to Alzheimer pathology in older people, including for people with an adverse ApoE haplotype.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1089\/rej.2011.1302","type":"journal-article","created":{"date-parts":[[2012,5,18]],"date-time":"2012-05-18T12:48:01Z","timestamp":1337345281000},"page":"395-404","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":25,"title":["Leukocyte\n                    <i>CCR2<\/i>\n                    Expression Is Associated with Mini-Mental State Examination Score in Older Adults"],"prefix":"10.1177","volume":"15","author":[{"given":"Lorna W.","family":"Harries","sequence":"first","affiliation":[{"name":"University of Exeter","place":["United Kingdom"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rachel M.","family":"Bradley-Smith","sequence":"additional","affiliation":[{"name":"University of Exeter","place":["United Kingdom"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David J.","family":"Llewellyn","sequence":"additional","affiliation":[{"name":"University of Exeter","place":["United Kingdom"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Luke C.","family":"Pilling","sequence":"additional","affiliation":[{"name":"University of Exeter","place":["United Kingdom"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alexander","family":"Fellows","sequence":"additional","affiliation":[{"name":"University of Exeter","place":["United Kingdom"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"William","family":"Henley","sequence":"additional","affiliation":[{"name":"University of Plymouth","place":["United Kingdom"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dena","family":"Hernandez","sequence":"additional","affiliation":[{"name":"National Institute on Aging"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jack M.","family":"Guralnik","sequence":"additional","affiliation":[{"name":"University of Maryland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stefania","family":"Bandinelli","sequence":"additional","affiliation":[{"name":"Geriatric Unit, Azienda Sanitaria Firenze, Florence, Italy."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andrew","family":"Singleton","sequence":"additional","affiliation":[{"name":"National Institute on Aging"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Luigi","family":"Ferrucci","sequence":"additional","affiliation":[{"name":"National Institute on Aging"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David","family":"Melzer","sequence":"additional","affiliation":[{"name":"University of Exeter","place":["United Kingdom"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"179","published-online":{"date-parts":[[2012,8]]},"reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.tics.2004.02.008"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature08983"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.2174\/157340009788167347"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1749-6632.2010.05726.x"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1742-4658.2010.07564.x"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1097-2765(00)80139-2"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1038\/nm1555"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature10357"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.neurobiolaging.2006.08.004"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.3233\/JAD-2009-0996"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1002\/gps.830"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2377-8-16"},{"key":"e_1_3_3_14_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1532-5415.2000.tb03873.x"},{"key":"e_1_3_3_15_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0010693"},{"key":"e_1_3_3_16_2","doi-asserted-by":"publisher","DOI":"10.1038\/ng1201-365"},{"key":"e_1_3_3_17_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jpsychires.2008.04.014"},{"key":"e_1_3_3_18_2","first-page":"203","article-title":"Mini-mental state. 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