Alzheimer's disease (AD) is marked by progressive cognitive decline and memory loss. Emerging evidence underscores the role of long non-coding RNAs (lncRNAs), particularly nuclearenriched abundant transcript 1 (NEAT1), in AD pathogenesis. NEAT1, a pivotal lncRNA that regulates diverse cellular processes, shows dysregulated expression in AD and impairs neuronal survival. This review explores NEAT1’s molecular mechanisms, biomarker potential, and therapeutic relevance. NEAT1 contributes to AD pathology by acting as a competitive endogenous RNA (ceRNA) that sequesters protective microRNAs, including miR-124 and miR-107, thereby dysregulating downstream targets. It facilitates PINK1 degradation and potentially drives mitochondrial dysfunction and neuronal injury. Elevated NEAT1 levels are associated with amyloid-beta accumulation, tau hyperphosphorylation, and NF-κB-mediated neuroinflammation. Preclinical studies suggest that modulating NEAT1 expression can alleviate AD‑like pathology, making NEAT1 a promising target for intervention. Increased plasma NEAT1 in patients indicates its value as a non-invasive early diagnostic biomarker. NEAT1 regulates multiple AD-related pathways, including IGF1R, TRAF2, BACE1, CREB/BDNF, and Nrf2/NQO1, and interacts with lncRNAs linked to metabolic and neurodegenerative diseases, such as XIST and KCNQ1OT1. By influencing amyloid processing, synaptic function, mitochondrial health, and inflammatory responses, NEAT1 emerges as a central regulator in AD. Targeting NEAT1 offers dual benefits: advancing precision diagnostics and enabling multi-pathway therapeutic approaches. This review underscores NEAT1’s significance as both a biomarker and therapeutic target, providing insights for future strategies to mitigate the burden of AD.
Zamanian et al. (Thu,) studied this question.