Lipids rapidly dissolve Alzheimer's disease plaques into toxic protofibrils, according to Joost Schymkowitz, Frederic Rousseau (Vrije Universiteit Brussel, Belgium), and colleagues.
Insoluble amyloid plaques of the Aβ protein are found throughout the Alzheimer's brain but are thought to be largely inert. By contrast, oligomeric protofibrils—the intermediate between soluble Aβ and insoluble amyloid—are known to be neurotoxic. But once they make plaques, protofibrils were not thought to escape back into toxic form.
Because disturbed lipid metabolism has been implicated in Alzheimer's development, the authors tested the effects of lipids on plaque solubility. When subjected to a variety of naturally occurring lipids, plaques released large amounts of protofibrils that were toxic to neurons in culture. Injecting a mixture of lipids and amyloids into the mouse brain caused memory deficits not seen with either alone. “If the brain harbors a lot of aggregates, it can be a significant reservoir of toxic material,” Rousseau says, which may contribute to worsening Alzheimer's disease.
As a silver lining, Rousseau notes, the discovery may make antiprotofibril antibody production much easier, because abundant quantities of protofibrils can be kept in solution for long periods.