Serum Aberrant Expression of Long Non-coding RNA LINC00365 and its Diagnostic Value in Alzheimer’s Disease

Background Alzheimer’s disease (AD) is the most prevalent neurodegenerative disorder. The present study aimed to elucidate the molecular mechanism underlying long non-coding RNA LINC00365 (LINC00365)-mediated regulation of AD pathogenesis. Methods A total of 135 AD patients and 135 healthy controls were enrolled. The expression of LINC00365, microRNA-429 (miR-429), and F-box and WD repeat domain-containing 7 (FBXW7) was measured by real-time quantitative polymerase chain reaction (RT-qPCR). In vitro, AD cell models were established by treating SH-SY5Y neuronal cells and BV2 microglial cells with amyloid-β25-35 (Aβ 25-35 ). Cell viability, apoptosis, and inflammatory cytokine levels were assessed using Cell Counting Kit-8 (CCK-8), flow cytometry, and enzyme-linked immunosorbent assay (ELISA), respectively. Subcellular localization of LINC00365 was analyzed by nuclear/cytoplasmic fractionation. The direct binding was validated by RNA immunoprecipitation (RIP) and dual-luciferase assays. Results Serum LINC00365 was markedly decreased in AD patients with potential diagnostic value, and its level declined as dementia severity increased. In vitro, LINC00365 overexpression significantly ameliorated Aβ 25-35 -induced reductions in SH-SY5Y cell viability and apoptosis, and suppressed the release of tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) from BV2 microglia. Mechanistically, cytoplasmic-localized LINC00365 directly sponged miR-429, and FBXW7 was verified as its downstream target. Rescue experiments showed that miR-429 mimic reversed LINC00365-mediated FBXW7 upregulation and neuroprotection, whereas FBXW7 overexpression restored cell viability, attenuated apoptosis, and reduced inflammatory cytokine levels. Conclusion LINC00365 showed potential diagnostic value for AD in the present cohort. Mechanistically, it acted as a competing endogenous RNA (ceRNA) to sponge miR-429, thus elevating FBXW7 and relieving Aβ 25 - 35 -triggered neuronal injury and neuroinflammation.