Twenty-five years have passed since researchers launched the idea that Alzheimer’s is a direct result of clumps of amyloid-beta littering the brain. The amyloid hypothesis of Alzheimer’s disease, as it is called, quickly raised hopes among researchers and patients alike that the dreaded disease would soon be under our control. But a cure seems as distant today as it did then.
So what have researchers concluded over the last 25 years, and why is the progress here so slow when other research fields are advancing by leaps and bounds?
The complex reality of simplicity
The amyloid hypothesis of Alzheimer’s disease
was simple. An imbalance in the production or removal of amyloid-beta was said to cause an accumulation and clumping of the peptide in the brain, which was toxic in itself and, in turn, set off a cascade of events leading to neurodegeneration and loss of brain tissue.
So if patients dying of Alzheimer’s disease have brains full of a protein that kills their nerve cells, the problem should be easily solved by removing the protein, researchers believed.
The idea born in the early 1990s was that if researchers learned the molecular secrets of the protein — asking questions like ‘what makes it aggregate,’ or ‘in what way does it kill neurons’ — it would just be a matter of time before a treatment, or even cure, could be developed. Unfortunately, the simple idea turned out to be a lot more complex than scientists imagined.
Studies of protein aggregation are arduous and slow tasks. The problem with protein aggregation is that, in contrast to studies of other cellular processes or structures, evolution has wor