For the past 25 years, efforts to develop a treatment for the disease have focused on the so-called “amyloid cascade hypothesis.” This proposes that amyloid-β (Aβ) peptides build up and clump together to form plaques in the brain, creating a cascade effect that ultimately leads to neuronal death and cognitive dysfunction.
However, despite evidence of a link between amyloid-β and Alzheimer’s disease, efforts to target the peptide have so far failed to reverse this cognitive decline.
Now, in a review paper published in the journal Nature, researchers at the Picower Institute for Learning and Memory at MIT argue that while elevated amyloid-β levels may initiate the sequence of events that lead to the disease, a complex series of other molecular, cellular, circuit and network-level changes contribute to its progression. What’s more, the researchers argue, these changes cannot be reversed simply by controlling amyloid-β levels.
Many of the treatments designed to target amyloid-β use antibodies to clear plaque from the brain, and are very effective in doing so, according to Li-Huei Tsai, the Picower Professor of Neuroscience and director of the Picower Institute for Learning and Memory at MIT.