The accumulation of Ղ-amyloid (AՂ) aggregates is a characteristic of Alzheimer's disease (AD). Furthermore, these aggregates have neurotoxic effects on cells, and thus, molecules that inhibit AՂ aggregate formation could be valuable therapeutics for AD. It is well known that aggregation of AՂ depends on its hydrophobicity, and thus, in order to increase the hydrophilicity of AՂ, we considered using citrate, an anionic surfactant with three carboxylic acid groups. We hypothesized that citrate could reduce hydrophobicity and increase hydrophilicity of AՂ1-40 molecules via hydrophilic/electrostatic interactions. We found that citrate significantly inhibited AՂ1-40 aggregation and significantly protected SH-SY5Y cell line against AՂ1-40 aggregates-induced neurotoxicity. In details, we examined the effects of citrate on AՂ1-40 aggregation and on AՂ1-40 aggregates-induced cytotoxicity, cell viability, and apoptosis. Th-T assays showed that citrate significantly inhibited AՂ1-40 aggregation in a concentration- dependent manner (Th-T intensity: from 91.3% in 0.01 mM citrate to 82.1% in 1.0 mM citrate vs. 100.0% in AՂ1-40 alone). In cytotoxicity and viability assays, citrate reduced the toxicity of AՂ1-40 in a concentration-dependent manner, in which the cytotoxicity decreased from 107.5 to 102.3% as compared with AՂ1-40 aggregates alone treated cells (127.3%) and the cell viability increased from 84.6 to 93.8% as compared with the AՂ1-40 aggregates alone treated cells (65.3%). Furthermore, Hoechst 33342 staining showed that citrate (1.0 mM) suppressed AՂ1-40 aggregates-induced apoptosis in the cells. This study suggests that citrate can inhibit AՂ1-40 aggregation and protect neurons from the apoptotic effects of AՂ1-40 aggregates. Accordingly, our findings suggest that citrate administration should be viewed as a novel neuroprotective strategy for AD.