The neuroinflammatory effects of acrolein on human microglial HMC3 cells in Alzheimer’s disease

Acrolein, a reactive compound, causes oxidative stress and inflammation, promoting neuroinflammation and Alzheimer’s disease (AD) risk. Both former and current smokers have an elevated AD risk, with smoking being the main source of acrolein exposure (500–2,800 µg in heavy smokers, 1.8–9 µg in e-cigarette users). This study investigated acrolein’s cytotoxic effects on human microglial HMC3 cells using MTT and LDH assays and its impact on neuroinflammatory cytokine production. Acrolein is cytotoxic at concentrations as low as 1–2 µg/mL, with significant cell death at 5 µg/mL. The study showed increased CD86 expression (M1 microglial activation) and elevated RAGE levels, a key AD biomarker. Higher IL-1β and TNF-α levels, linked to NF-κB activation suggest that acrolein increases the AD risk. With 12.5% of U.S. adults smoking, these findings are significant. Further research should explore acrolein’s effects in stem cell cultures, 3D blood–brain barrier models, and in vivo systems.