The current hypothesis is well understood among the scientific community: amyloid plaques—or toxic clusters of damaged proteins between cells—composed of beta-amyloid peptides result in neurodegeneration and eventually Alzheimer’s disease.
Published in the October issue of the Journal of Neuroscience, however, comes a divergent new theory: It is in fact the inability of neurons to secrete beta-amyloid that is behind the pathogenesis of Alzheimer’s.
The study, from Swedish researchers at Lund University, shows an increase in unwanted intracellular beta-amyloid occurring early on in Alzheimer’s. The accumulation of beta-amyloid inside the neuron is here shown to be caused by the loss of normal function to secrete beta-amyloid.
“We are showing here that the increase of intracellular beta-amyloid is one of the earliest events occurring in Alzheimer's disease, before the formation of plaques,” researchers said. “Our experiments clearly show a decreased secretion of beta-amyloid in our primary neuron disease model.
“This is probably because the cell's metabolism and secretion pathways are disrupted in some way, leading beta-amyloid to be accumulated inside the cell instead of being secreted naturally.”
The damage to the neuron, created by the aggregated toxic beta-amyloid inside the cell, is believed to be a prior step to the formation of plaques, the long-time hallmark biomarker of Alzheimer’s, according to the study.
The theory of early accumulation of beta-amyloid inside the cell offers an alternate explanation for the formation of plaques, researchers said. When excess amounts of beta-amyloid start to build up inside the cell, it is also stored in synapses. When synapses can no longer hold the increasing amounts of the toxic peptide, the membrane breaks, thereby releasing the waste into the extracellular space.
The toxins released now create the seed for other amyloids to gather and start forming the plaques, argued the researchers, who hope their findings signal a different direction in Alzheimer’s research and eventually treatment.