{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,5]],"date-time":"2026-06-05T14:19:10Z","timestamp":1780669150537,"version":"3.54.1"},"reference-count":42,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2022,7,8]],"date-time":"2022-07-08T00:00:00Z","timestamp":1657238400000},"content-version":"vor","delay-in-days":188,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":["alz-journals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["A&D Transl Res & Clin Interv"],"published-print":{"date-parts":[[2022,1]]},"abstract":"Abstract<\/jats:title>\n \n Introduction<\/jats:title>\n \n Human study shows that elevated C\u2010reactive protein (CRP) in blood impacts apolipoprotein E (\n APOE<\/jats:italic>\n ) \u03b54, but not\n APOE<\/jats:italic>\n \u03b53 or\n APOE<\/jats:italic>\n \u03b52, genotype to increase the risk of Alzheimer's disease (AD). However, whether CRP is directly involved in cellular AD pathogenesis and in which type of neuronal cells of\n APOE<\/jats:italic>\n \u03b54 carriers are unknown.\n <\/jats:p>\n <\/jats:sec>\n \n Methods<\/jats:title>\n \n We aimed to use different primary neuronal cells and investigate if CRP induces cellular AD pathology depending on\n APOE<\/jats:italic>\n genotypes. Here the different primary neuronal cells from the different\n APOE<\/jats:italic>\n genotype knock\u2010in mice cortex were isolated and used.\n <\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n Monomeric CRP (mCRP) increased amyloid beta production and, in parallel, induced tau phosphorylation in addition to their related proteins in the primary neurons in a pattern of\n APOE<\/jats:italic>\n \u03b54 >\u00a0\n APOE<\/jats:italic>\n \u03b53 >\u00a0\n APOE<\/jats:italic>\n \u03b52 in a dose\u2010 and time\u2010dependent manner. Consistently, mCRP induced the staining of other neurodegenerative biomarkers, including Fluoro\u2010Jade B stain (FjB), TUNEL and Cleaved Caspase\u20103, in primary neurons in a similar pattern of\n APOE<\/jats:italic>\n \u03b54 >\u00a0\n APOE<\/jats:italic>\n \u03b53 >\u00a0\n APOE<\/jats:italic>\n \u03b52. In contrast, pentameric CRP (pCRP) had a tendency to induce cellular AD pathology but did not reach statistical significance. On the other hand, it is intriguing that regardless of\n APOE<\/jats:italic>\n genotype, mCRP did not influence the expressions of Iba\u20101 and CD68 in primary microglia or the expression of glial fibrillary acidic protein in primary astrocytes, and additionally mCRP did not affect the secretions of interleukin (IL)\u20101\u03b1, IL\u20101\u03b2, and tumor necrosis factor \u03b1 from these cells.\n <\/jats:p>\n <\/jats:sec>\n \n Discussion<\/jats:title>\n \n This is the first report to demonstrate that mCRP directly induces cellular AD pathogenesis in neurons in an\n APOE<\/jats:italic>\n genotype\u2010dependent pattern, suggesting that mCRP plays a role as a mediator involved in the\n APOE<\/jats:italic>\n \u03b54\u2010related pathway for AD during chronic inflammation.\n <\/jats:p>\n <\/jats:sec>\n \n Highlights<\/jats:title>\n \n \n \n Pentameric C\u2010reactive protein (pCRP) can be dissociated irreversibly to form free subunits or monomeric CRP (mCRP) during and after the acute phase.<\/jats:p>\n <\/jats:list-item>\n \n \n mCRP increased amyloid beta production in the primary neurons in a pattern of apolipoprotein E (\n APOE<\/jats:italic>\n ) \u03b54\u00a0>\u00a0\n APOE<\/jats:italic>\n \u03b53 >\u00a0\n APOE<\/jats:italic>\n \u03b52 in a dose\u2010dependent manner.\n <\/jats:p>\n <\/jats:list-item>\n \n \n mCRP induced the expression of phosphorylated tau in the primary neurons in a pattern of\n APOE<\/jats:italic>\n \u03b54 >\u00a0\n APOE<\/jats:italic>\n \u03b53 >\u00a0\n APOE<\/jats:italic>\n \u03b52 in a dose\u2010 and time\u2010dependent manner.\n <\/jats:p>\n <\/jats:list-item>\n \n \n mCRP plays an important mediator role in the\n APOE<\/jats:italic>\n \u03b54\u2010related pathway of Alzheimer's disease risk.\n <\/jats:p>\n <\/jats:list-item>\n <\/jats:list>\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1002\/trc2.12319","type":"journal-article","created":{"date-parts":[[2022,7,9]],"date-time":"2022-07-09T02:26:05Z","timestamp":1657333565000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["Monomeric C\u2010reactive protein induces the cellular pathology of Alzheimer's disease"],"prefix":"10.1002","volume":"8","author":[{"given":"Qini","family":"Gan","sequence":"first","affiliation":[{"name":"Department of Pharmacology and Experimental Therapeutics Boston University School of Medicine Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alfred","family":"Wong","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Experimental Therapeutics Boston University School of Medicine Boston Massachusetts 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