Formation of spherulitic amyloid ß aggregate by anionic liposomes.

Alzheimer's disease is the most common form of senile dementia. This neurodegenerative disorder is characterized by an amyloid deposition in senile plaques, composed primarily of fibrils of an aggregated peptide, amyloid ß (Aß). The modeling of a senile plaque formation on a model neuronal membrane under the physiological condition is an attractive issue. In this study, we used anionic liposomes to model the senile plaque formation by Aß. The growth behavior of amyloid Aß fibrils was directly observed, revealing that the induction of the spherulitic Aß aggregates could result from the growth of seeds in the presence of anionic liposomes. The seeds of Aß fibrils strongly interacted with negatively charged liposome and the subsequent association of the seeds were induced to form the seed cluster with many growth ends, which is advantageous for the formation of spherulitic Aß aggregates. Therefore, anionic liposomes mediated not only fibril growth but also the aggregation process. These results imply that anionic liposome membranes would affect the aggregate form of Aß fibrils. The modeling of senile plaque reported here is considered to have great potential for study on the amyloidosis.

Copper-mediated growth of amyloid ß fibrils in the presence of oxidized and negatively charged liposomes.

Amyloid ß protein (Aß) from Alzheimer's disease formed fibrillar aggregates and their morphology depended on oxidized and negatively charged liposomes. The morphology of fibrillar aggregates was affected by Cu(2+), together with their growth kinetics. This is because Cu(2+) inhibited the nucleation step in the formation of amyloid Aß fibrillar aggregates by forming Aß/Cu complex inactive to the growth of fibrillar aggregates. In addition, this is probably because Cu(2+) affected the fibrillar aggregate formed on the surface of liposomes. These findings would give a better understanding of the formation mechanism of amyloid fibrils on biomembranes.