New mechanism identified that is potentially linked to very early stages of Alzheimer’s

An excess of fragments of amyloid precursor protein (APP), called APP-CTFs, can trigger a mechanism that occurs at the early stages of Alzheimer’s disease. The researchers say understanding the role of APP-CTFs could open avenues for early intervention therapies that could stop or even prevent Alzheimer’s disease.

For the past two decades, Alzheimer’s research has focused on events that occur much later on in the disease: amyloid-β plaques in the brain and, more recently, the presence of tau and microglia. ‘To prevent Alzheimer’s disease we need to understand what happens in the brain before the typical hallmarks appear: this can be up to 10 years before a clinical diagnosis is set,’ says senior author Wim Annaert at KU Leuven and VIB-Center for Brain and Disease Research in Belgium. Previous studies have shown that abnormal endosomes and lysosomes in neurons occur long before amyloid plaques appear and are common in both forms of Alzheimer’s disease, familial and sporadic. And although toxic APP-CTF has been linked to this dysfunction, nobody has been able to really join the dots. Until now.