A Novel Competing Endogenous RNA Linked to Dysregulated Neuroinflammation in Alzheimer’s Disease

Alzheimer’s disease (AD) is an aging-associated neurodegenerative disorder in which dysregulated neuroinflammation drives disease progression. Although long noncoding RNAs (lncRNAs) are increasingly implicated in AD, their mechanistic roles remain poorly defined. Here, we identified a novel lncRNA termed LIMASI (LncRNA Inflammation and Mucous associated, Antisense to ICAM1), that is linked with AD-associated neuroinflammation. LIMASI expression is significantly elevated in postmortem AD brain tissues and in the 3xTg-AD mouse model by qPCR and RNA fluorescence in situ hybridization, and its upregulation correlated with increased β-amyloid plaque burden, tau hyperphosphorylation, and heightened neuroinflammatory activation. Cell-type–specific analyses demonstrated inflammation-inducible LIMASI expression in astrocytes and microglia. In an in vitro model of AD-associated neuroinflammation, viral-mimetic poly(I:C) challenge of amyloid precursor protein (APP)–overexpressing neuroblastoma cells elicited coordinated induction of LIMASI and key inflammatory mediators. Mechanistically, computational RNA–RNA interaction modeling predicted multiple energetically favorable binding sites for AD-associated inflammatory microRNAs (miR-1915-3p, miR-122-5p, miR-155-5p, and miR-150-5p), supporting a competing endogenous RNA (ceRNA) model in which LIMASI sequesters miRNAs to modulate neuroinflammatory gene networks. Together, these data identify LIMASI as a putative ceRNA strongly linked to AD-related neuroinflammation and suggest that LIMASI represents a promising therapeutic target for modulating neuroinflammatory signaling and slowing AD-associated neurodegeneration.