Abstract <p>Alzheimer’s disease (AD) remains an incurable, progressive neurodegenerative disorder that features neuronal network degradation, dementia, neuroinflammation, depression, and amyloidosis. The study aimed to determine the effective duration of intranasal administration of a liposomal curcumin (Cur) spray and microRNA-101 (miR-101) in a rat model of Alzheimer’s disease. The investigators measured concentrations of endogenous β-amyloid peptide 40 (Rat_Aβ 1-40), endothelial NO synthase (eNOS), and cytokines, including interleukin-1β (IL-1β), tumor necrosis factor α (TNFα), and interleukin-6 (IL-6), in homogenates of the neocortex and hippocampus of rat brains. They quantified these analytes with immunoassay techniques using the corresponding ELISA Kit (Elabscience, United States) and normalized the results to milligrams of total protein in each sample, which they measured with the Lowry method. The investigators found that rats with AD and no treatment showed an increase in Rat_Aβ 1-40 concentration in the hippocampus on days 10–20 of disease progression, and only on day 30 in the neocortex. Intranasal therapy with a liposomal Cur + miR-101 spray produced an anti-amyloidogenic effect starting on day 5 of treatment in both brain regions. The anti-inflammatory effect of intranasal Cur + miR-101 appeared on day 15 for IL-1β, TNFα, and IL-6 because curcumin suppresses transcription of their genes. The liposomal Cur + miR-101 spray also showed antioxidant activity across all treatment intervals in the neocortex and hippocampus of rats with the AD model, along with an increase in eNOS content on days 10, 20, and 30 of the disease in the hippocampus, and on days 20 and 30 in the neocortex of untreated rats. The study demonstrated the anti-amyloidogenic, anti-inflammatory, and antioxidant effects of intranasal therapy with a liposomal curcumin and microRNA-101 spray in the hippocampus and neocortex in AD. The investigators established that the effective treatment duration should last at least 15 days.</p>