How Do Lipids Localize in Lewy Bodies?

Lewy bodies are the pathological hallmark of Parkinson's disease (PD). While fibrillar α-synuclein (αS) is the main protein component of Lewy bodies, these structures also contain lipids. To elucidate the presence of lipids in Lewy bodies, we investigated the interaction of lipids with monomeric and fibrillar αS. In vitro, lipid membranes accelerated αS fibril formation under physiological conditions. Moreover lipids and small vesicles co-localized with supra-fibrillar structures and individual αS fibrils suggesting that aggregation initiates at the membrane. The presence of lipids in Lewy bodies may therefore be an indication that cell membranes are the major target in aggregation induced neuronal cell deat