A research study, published yesterday (Tuesday, 12 April 2011) in the Journal of the American Chemical Society (JACS), demonstrates that the aggregation of amyloid-beta (Aβ) proteins into amyloid fibrils characteristic of Alzheimer's disease (AD) is not irreversible, as previously thought. The Aβ protein molecules that comprise the fibrils are continuously detaching from and re-attaching to the fibrils, resulting in molecular recycling. These findings suggest that recycling could be a source of small non-fibrillar Aβ aggregates, which are believed to be responsible for the neurodegeneration observed in AD. The authors of this study, experts in protein structure and aggregation at IRB Barcelona and other research centers, led by the ICREA researcher Nàtalia Carulla, believe that modulation of fibril recycling may lead to the development of new therapeutic approaches to treat this disease.
New insights into the dynamics of amyloid fibrils
AD is a progressive neurodegenerative disease characterized by the presence of amyloid plaques in the brain. Previous analysis of these plaques revealed that their main constituents are fibrillar aggregates of the Aβ protein known as amyloid fibrils. This is the reason why initial studies proposed that Aβ fibrils caused the disease. Later, it was observed that there were only weak correlations between levels of amyloid fibrils in the brain and the severity of dementia. This finding led to the formulation of new hypotheses in which small Aβ protein aggregates formed before the development of fibrils are thought to be responsible for neurodegeneration. Recent data have shown that fibrillar plaques are a potential reservoir of small toxic Aβ protein aggregates. In this scenario, "understanding the molecular basis of the disease requires knowledge about the interconversion between the different species present during Aβ protein aggregation", says Carulla.