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.

Catechol derivatives inhibit the fibril formation of amyloid-beta peptides.

The inhibition of fibril formation of amyloid beta proteins (A beta) would be attractive therapeutic targets for the treatment of Alzheimer's disease (AD). Dopamine (DA) and other catechol derivatives were used as inhibitory factors for A beta fibril formation. The fibril formation of A beta was monitored by Thioflavin T fluorescence, a transmission electron microscopy (TEM) and a total internal reflection fluorescence microscopy (TIRFM). Catechol and its derivatives showed the dose-dependent inhibitory effects on the spontaneous A beta fibril formation. The inhibitory activity depended on the chemical structure of catechol derivatives both in the presence and absence of the liposome a model of biomembrane. Formation of catechol quinone-conjugated-A beta adduct by a Schiff-base is a key step for the inhibition effect of A beta fibril formation.