{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,28]],"date-time":"2026-04-28T17:16:18Z","timestamp":1777396578855,"version":"3.51.4"},"reference-count":69,"publisher":"SAGE Publications","issue":"2","license":[{"start":{"date-parts":[[2019,1,21]],"date-time":"2019-01-21T00:00:00Z","timestamp":1548028800000},"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":["Journal of Alzheimer\u2019s Disease"],"published-print":{"date-parts":[[2019,1,22]]},"abstract":"<jats:p>Alzheimer\u2019s disease (AD), associated with abnormal accumulation of amyloid-\u03b2 (A\u03b2), is the most common cause of dementia among older people. A few studies have identified substantial AD biomarkers in blood but their results were inconsistent. Here we screened gene expression alterations on A\u03b2-GFP SH-SY5Y neuronal model for AD, and evaluated the findings on peripheral leukocytes from 78 patients with AD and 56 healthy controls. The therapeutic responses of identified biomarker candidates were further examined in A\u03b2-GFP SH-SY5Y neuronal and APP\/PS1\/Tau triple transgenic (3\u00d7Tg-AD) mouse models. Downregulation of apolipoprotein E (APOE) and tropomyosin receptor kinase A (TRKA) were detected in A\u03b2-GFP SH-SY5Y cells and validated by peripheral leukocytes from AD patients. Treatment with an in-house indole compound NC009-1 upregulated the expression of APOE and TRKA accompanied with improvement of neurite outgrowth in A\u03b2-GFP SH-SY5Y cells. NC009-1 further rescued the downregulated APOE and TRKA and reduced A\u03b2 and tau levels in hippocampus and cortex, and ameliorated cognitive deficits in streptozocin-induced hyperglycemic 3\u00d7Tg-AD mice. These results suggest the role of APOE and TRKA as potential peripheral biomarkers in AD, and offer a new drug development target of AD treatment. Further studies of a large series of AD patients will be warranted to verify the findings and confirm the correlation between these markers and therapeutic efficacy.<\/jats:p>","DOI":"10.3233\/jad-180643","type":"journal-article","created":{"date-parts":[[2019,1,22]],"date-time":"2019-01-22T18:25:28Z","timestamp":1548181528000},"page":"737-756","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":19,"title":["Indole Compound NC009-1 Augments APOE and TRKA in Alzheimer\u2019s Disease Cell and Mouse Models for Neuroprotection and Cognitive Improvement"],"prefix":"10.1177","volume":"67","author":[{"given":"Yi-Chun","family":"Chen","sequence":"first","affiliation":[{"name":"Department of Neurology, Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Taoyuan, 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