The papers by Ma and Lindquist are important to AD research. Unlike most other neurodegenerative diseases, AD and prion diseases have in common that both are characterized by dementia and "extracellular" plaques. The present papers demonstrate that increasing the intracellular "cytosolic" pool of PrP (i.e., by inhibition of the proteasome) is especially critical for neurotoxicity. In Alzheimer's research, a growing number of articles are also suggesting that β-amyloid accumulates within neurons and that intracellular Aβ may be neurotoxic. For example, just this year Zhang et al.
reported that Aβ1-42, but not Aβ42-1 or Aβ1-40, was highly neurotoxic when introduced intracellularly, and Busciglio et al.
reported that in Down's syndrome Aβ-accumulating neurons showed signs of apoptosis, see related news item
Still, the view that...