Parkinson disease (PD) is characterized by the progressive loss of dopaminergic neurons caused by alpha-synuclein (αSyn) aggregation. Although the toxicity of the existing αSyn has been studied extensively, the upstream of the αSyn aggregation hasn’t been elucidated so far. Previously, our team has revealed by FT-IR spectroscopy that the lipid content is rich in the Lewy body inclusion in the brain of PD patients and hypothesized that the aggregation of αSyn can be initiated by the accumulation of some lipids in the neuron. In accordance with this hypothesis, it has been known that about 10 % of PD patients possess the mutation in glucocerebrosidase (GBA), leading to the accumulation of Glucosylceramide; however, in the remaining 90 % of the sporadic cases, the upstream cause of the αSyn aggregation has not been elucidated. Therefore, we performed the screening of the lipids interacting with αSyn and inducing the aggregation and found that phosphatidylinositol-3-phosphate (PIP3) strongly affects αSyn aggregation. Interestingly, the αSyn fibril created with PIP3 showed similar structural features to the fibrils amplified from the PD patient's brain, indicating that PIP3 plays a role in the PD brain. We confirmed that PIP3 is indeed accumulated in the PD brain and the accumulation of PIP3 induces αSyn aggregation in cultured cells, primary cortical neurons, and C. elegans. We are currently performing drug development targeting the aberrant interactions between PIP3 and αSyn as a preventive therapy against the development of PD.