{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T03:00:39Z","timestamp":1791342039678,"version":"4.3.1"},"reference-count":50,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2021,3,24]],"date-time":"2021-03-24T00:00:00Z","timestamp":1616544000000},"content-version":"vor","delay-in-days":82,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["alz-journals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["A&amp;D Transl Res &amp; Clin Interv"],"published-print":{"date-parts":[[2021,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>Inflammatory markers have long been observed in the brain, cerebrospinal fluid (CSF), and plasma of Alzheimer's disease (AD) patients, suggesting that inflammation contributes to AD and might be a therapeutic target. However, non\u2010steroidal anti\u2010inflammatory drug trials in AD and mild cognitive impairment (MCI) failed to show benefit. Our previous work seeking to understand why people with the inflammatory disease rheumatoid arthritis are protected from AD found that short\u2010term treatment of transgenic AD mice with the pro\u2010inflammatory cytokine granulocyte\u2010macrophage colony\u2010stimulating factor (GM\u2010CSF) led to an increase in activated microglia, a 50% reduction in amyloid load, an increase in synaptic area, and improvement in spatial memory to normal. These results called into question the consensus view that inflammation is solely detrimental in AD. Here, we tested our hypothesis that modulation of the innate immune system might similarly be used to treat AD in humans by investigating the ability of GM\u2010CSF\/sargramostim to safely ameliorate AD symptoms\/pathology.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>A randomized, double\u2010blind, placebo\u2010controlled trial was conducted in mild\u2010to\u2010moderate AD participants (NCT01409915). Treatments (20 participants\/group) occurred 5 days\/week for 3 weeks plus two follow\u2010up (FU) visits (FU1 at 45 days and FU2 at 90 days) with neurological, neuropsychological, blood biomarker, and imaging assessments.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Sargramostim treatment expectedly changed innate immune system markers, with no drug\u2010related serious adverse events or amyloid\u2010related imaging abnormalities. At end of treatment (EOT), the Mini\u2010Mental State Examination score of the sargramostim group increased compared to baseline (\n                      <jats:italic>P<\/jats:italic>\n                      \u00a0=\u00a0.0074) and compared to placebo (\n                      <jats:italic>P<\/jats:italic>\n                      \u00a0=\u00a0.0370); the treatment effect persisted at FU1 (\n                      <jats:italic>P<\/jats:italic>\n                      \u00a0=\u00a0.0272). Plasma markers of amyloid beta (A\u03b240 [decreased in AD]) increased 10% (\n                      <jats:italic>P<\/jats:italic>\n                      \u00a0=\u00a0.0105); plasma markers of neurodegeneration (total tau and UCH\u2010L1) decreased 24% (\n                      <jats:italic>P<\/jats:italic>\n                      \u00a0=\u00a0.0174) and 42% (\n                      <jats:italic>P<\/jats:italic>\n                      \u00a0=\u00a0.0019), respectively, after sargramostim treatment compared to placebo.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Discussion<\/jats:title>\n                    <jats:p>The innate immune system is a viable target for therapeutic intervention in AD. An extended treatment trial testing the long\u2010term safety and efficacy of GM\u2010CSF\/sargramostim in AD is warranted.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/trc2.12158","type":"journal-article","created":{"date-parts":[[2021,3,24]],"date-time":"2021-03-24T08:01:40Z","timestamp":1616572900000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":74,"title":["Safety and efficacy of sargramostim (GM\u2010CSF) in the treatment of Alzheimer's disease"],"prefix":"10.1002","volume":"7","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4051-2516","authenticated-orcid":false,"given":"Huntington","family":"Potter","sequence":"first","affiliation":[{"name":"Department of Neurology University of Colorado School of Medicine  Aurora Colorado USA"},{"name":"University of Colorado Alzheimer's and Cognition Center  Aurora Colorado USA"},{"name":"Linda Crnic Institute for Down Syndrome University of Colorado School of Medicine  Aurora Colorado USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jonathan H.","family":"Woodcock","sequence":"additional","affiliation":[{"name":"Department of Neurology University of Colorado School of Medicine  Aurora Colorado USA"},{"name":"University of Colorado Alzheimer's and Cognition Center  Aurora Colorado USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Timothy D.","family":"Boyd","sequence":"additional","affiliation":[{"name":"University of Colorado Alzheimer's and Cognition Center  Aurora Colorado USA"},{"name":"Linda Crnic Institute for Down Syndrome University of Colorado School of Medicine  Aurora Colorado USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christina M.","family":"Coughlan","sequence":"additional","affiliation":[{"name":"Department of Neurology University of Colorado School of Medicine  Aurora Colorado USA"},{"name":"University of Colorado Alzheimer's and Cognition Center  Aurora Colorado USA"},{"name":"Linda Crnic Institute for Down Syndrome University of Colorado School of Medicine  Aurora Colorado USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John R.","family":"O'Shaughnessy","sequence":"additional","affiliation":[{"name":"Department of Neurology University of Colorado School of Medicine  Aurora Colorado USA"},{"name":"University of Colorado Alzheimer's and Cognition Center  Aurora Colorado USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manuel T.","family":"Borges","sequence":"additional","affiliation":[{"name":"Department of Neurology University of Colorado School of Medicine  Aurora Colorado USA"},{"name":"Department of Radiology University of Colorado School of Medicine  Aurora Colorado USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ashesh A.","family":"Thaker","sequence":"additional","affiliation":[{"name":"Department of Neurology University of Colorado School of Medicine  Aurora Colorado USA"},{"name":"Department of Radiology University of Colorado School of Medicine  Aurora Colorado USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Balaibail A.","family":"Raj","sequence":"additional","affiliation":[{"name":"University of South Florida School of Medicine  Tampa Florida USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katarzyna","family":"Adamszuk","sequence":"additional","affiliation":[{"name":"Bioclinica  Newark California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Scott","sequence":"additional","affiliation":[{"name":"Bioclinica  Newark California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vanesa","family":"Adame","sequence":"additional","affiliation":[{"name":"University of Colorado Alzheimer's and Cognition Center  Aurora Colorado USA"},{"name":"Linda Crnic Institute for Down Syndrome University of Colorado School of Medicine  Aurora Colorado USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paige","family":"Anton","sequence":"additional","affiliation":[{"name":"University of Colorado Alzheimer's and Cognition Center  Aurora Colorado USA"},{"name":"Linda Crnic Institute for Down Syndrome University of Colorado School of Medicine  Aurora Colorado USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Heidi J.","family":"Chial","sequence":"additional","affiliation":[{"name":"Department of Neurology University of Colorado School of Medicine  Aurora Colorado USA"},{"name":"University of Colorado Alzheimer's and Cognition Center  Aurora Colorado USA"},{"name":"Linda Crnic Institute for Down Syndrome University of Colorado School of Medicine  Aurora Colorado USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Helen","family":"Gray","sequence":"additional","affiliation":[{"name":"Department of Neurology University of Colorado School of Medicine  Aurora Colorado USA"},{"name":"University of Colorado Alzheimer's and Cognition Center  Aurora Colorado USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joseph","family":"Daniels","sequence":"additional","affiliation":[{"name":"Department of Neurology University of Colorado School of Medicine  Aurora Colorado USA"},{"name":"University of Colorado Alzheimer's and Cognition Center  Aurora Colorado USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michelle E.","family":"Stocker","sequence":"additional","affiliation":[{"name":"Department of Neurology University of Colorado School of Medicine  Aurora Colorado USA"},{"name":"University of Colorado Alzheimer's and Cognition Center  Aurora Colorado USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefan H.","family":"Sillau","sequence":"additional","affiliation":[{"name":"Department of Neurology University of Colorado School of Medicine  Aurora Colorado USA"},{"name":"University of Colorado Alzheimer's and Cognition Center  Aurora Colorado USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2021,3,24]]},"reference":[{"key":"e_1_2_8_2_1","volume-title":"Beyond beta protein\u2014the essential role of inflammation","author":"Potter H","year":"2001"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1111\/jnc.13667"},{"key":"e_1_2_8_4_1","first-page":"337","article-title":"Foe or Both?","volume":"11","author":"Frost GR","year":"2019","journal-title":"Immune Activity in Alzheimer's Disease"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1111\/jnc.14674"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.47.2.425"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.3233\/JAD-2006-9S330"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jalz.2014.03.009"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.3233\/JAD-2010-091471"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jneuroim.2018.03.009"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature22067"},{"key":"e_1_2_8_12_1","first-page":"1000101","article-title":"Granulocyte macrophage colony stimulating factor treatment is associated with improved cognition in cancer patients","volume":"1","author":"Jim HS","year":"2012","journal-title":"Brain disorders & therapy"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.CIR.0000074209.17561.99"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.brainres.2006.03.059"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.STR.0000259707.43496.71"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1161\/STROKEAHA.107.503433"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.3171\/2008.12.JNS08172"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1111\/ejn.13105"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.3171\/2014.8.SPINE131090"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jns.2008.10.022"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.1089\/neu.2013.3106"},{"key":"e_1_2_8_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jneuroim.2014.11.002"},{"key":"e_1_2_8_23_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00417-012-1932-9"},{"key":"e_1_2_8_24_1","doi-asserted-by":"publisher","DOI":"10.1002\/jnr.23205"},{"key":"e_1_2_8_25_1","doi-asserted-by":"publisher","DOI":"10.1097\/00001756-200410050-00003"},{"key":"e_1_2_8_26_1","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2202-8-88"},{"key":"e_1_2_8_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neures.2007.01.015"},{"key":"e_1_2_8_28_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10495-010-0552-2"},{"key":"e_1_2_8_29_1","doi-asserted-by":"publisher","DOI":"10.1038\/srep00697"},{"key":"e_1_2_8_30_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neurobiolaging.2018.12.019"},{"key":"e_1_2_8_31_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13195-015-0151-0"},{"key":"e_1_2_8_32_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jbi.2008.08.010"},{"key":"e_1_2_8_33_1","unstructured":"PartnerTherapeuticsInc. Leukine [package insert]. Lexington MA2018."},{"key":"e_1_2_8_34_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.clim.2019.108292"},{"key":"e_1_2_8_35_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms20040834"},{"key":"e_1_2_8_36_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10654-018-0381-0"},{"key":"e_1_2_8_37_1","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.319.7203.185"},{"key":"e_1_2_8_38_1","doi-asserted-by":"publisher","DOI":"10.1001\/archinte.158.9.1021"},{"key":"e_1_2_8_39_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jalz.2018.02.018"},{"key":"e_1_2_8_40_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature25456"},{"key":"e_1_2_8_41_1","doi-asserted-by":"publisher","DOI":"10.1038\/srep26801"},{"key":"e_1_2_8_42_1","doi-asserted-by":"publisher","DOI":"10.3389\/fnagi.2017.00226"},{"key":"e_1_2_8_43_1","doi-asserted-by":"publisher","DOI":"10.1159\/000447239"},{"key":"e_1_2_8_44_1","doi-asserted-by":"publisher","DOI":"10.1080\/14728222.2017.1321635"},{"key":"e_1_2_8_45_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jalz.2014.07.003"},{"key":"e_1_2_8_46_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroimage.2018.11.019"},{"key":"e_1_2_8_47_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1460-9568.2009.06653.x"},{"key":"e_1_2_8_48_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.nbd.2011.02.011"},{"key":"e_1_2_8_49_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jneuroim.2013.10.009"},{"key":"e_1_2_8_50_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41531-017-0013-5"},{"key":"e_1_2_8_51_1","first-page":"489428","article-title":"Apolipoprotein e: essential catalyst of the Alzheimer amyloid cascade","volume":"2012","author":"Potter H","year":"2012","journal-title":"Int J Alzheimers Dis"}],"container-title":["Alzheimer's &amp; Dementia: Translational Research &amp; Clinical Interventions"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/trc2.12158","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/trc2.12158","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/alz-journals.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/trc2.12158","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,26]],"date-time":"2025-10-26T12:13:55Z","timestamp":1761480835000},"score":1,"resource":{"primary":{"URL":"https:\/\/alz-journals.onlinelibrary.wiley.com\/doi\/10.1002\/trc2.12158"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,1]]},"references-count":50,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2021,1]]}},"alternative-id":["10.1002\/trc2.12158"],"URL":"https:\/\/doi.org\/10.1002\/trc2.12158","archive":["Portico"],"relation":{},"ISSN":["2352-8737","2352-8737"],"issn-type":[{"value":"2352-8737","type":"print"},{"value":"2352-8737","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,1]]},"assertion":[{"value":"2021-01-20","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2021-02-05","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2021-03-24","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e12158"}}