(544e) Anthocyanidins Modulate Amyloid-? Aggregation and Attenuate Reactive Oxygen Species Associated With Alzheimer's Disease Pathogenesis

Alzheimer’s disease (AD), one of the most widespread neurodegenerative diseases, is characterized by confusion, language skill breakdown, long-term memory loss and other cognitive impairments. Existing therapies for AD only provide symptomatic benefits but do not stop or slow AD pathogenesis. Increasing evidence revealing the multi-factorial nature of AD suggests that a multi-target treatment may be an effective therapeutic strategy.

The generation of excess reactive oxygen species (ROS) has been detected in AD brain, and epidemiological studies have demonstrated a correlation between increased intake of antioxidant capable polyphenols and reduced incidence of AD. On the other hand, polyphenols such as tyrosol, resveratrol, and epicatechin have been reported for their capability to alter the formation of amyloid-β protein (Aβ) aggregates, which deposit to form amyloid plaques that are a hallmark of AD pathology. Anthocyanidins (ACs) are a group of polyphenols commonly found in daily diets, such as blueberries and purple cabbages. In this study, a family of ACs was studied for their ability to serve as multi-target agents for AD.

Conformational-specific antibodies were utilized to detect the appearance of fibrillar Aβ species during monomer aggregation. ACs all showed some ability to reduce the formation of fibrillar Aβ species. Moreover, inhibitory capability correlates with the number of hydroxyl groups on the 6-membered aromatic ring. ACs also extended the lag time to aggregate formation. Thus, their ability to inhibit Aβ oligomerization was also examined and confirmed for ACs that have a larger number of hydroxyl groups. An oxygen radical absorbance capacity (ORAC) assay was further introduced to evaluate the anti-oxidant activity of selected ACs. All ACs showed significant anti-oxidant activity. In summary, ACs are promising compounds that not only reduce Aβ aggregate formation, but also attenuate ROS to serve as multi-target drugs for AD.