Surprising Twist in Pathogenesis of Alzheimer Disease

Although the association was controversial when it was first reported in 1990 (JW Nov 2 1990), most people now accept that soluble amyloid-β peptide fragments are central to the pathology of Alzheimer disease. In rodents, when amyloid-β enters a neuron, it reduces the number of dendritic spines and impairs memory. The theory that prions (proteins that propagate without nucleic acid) cause neurodegeneration in many mammals, including humans, also was highly controversial when first postulated but now is widely accepted. Prions destroy neurons by deforming a healthy protein (PrP^C) and transforming it into a pathologic protein. Normal PrP^C is a neuronal receptor.

A team from Yale looked for a receptor that allows amyloid-β to enter cells, which…