New Twist On Tangles: Research conducted by Penn's John Trojanowski and Virginia Lee suggests that phosphatases may be "lazy," or inactive, in Alzheimer's tangles.
"Up until this paper came out, the thinking in the field was that tau, which is the backbone of PHFs in neurofibrullary tangles, are so-called abnormally phosphorylated," says Lee. "In the early 1990s, researchers thought that all of these sites in PHF-tau were 'abnormal' because nobody was able to find them in normal tau isolated from postmortem human brains. As we were trying to understand the nature of the hyperphosphorylation of PHF-tau, we found that these phosphate sites accept or are actually occupied by phosphates in the fetal form of tau, but not in the normal postmortem human brain [G.T. Bramblett et al., Neuron, 10:1089-99, 1993; M. Goedert et al., Proceedings of the National Academy of Sciences, 90:5066-70, 1993].
"This discrepancy struck us as being odd. ...
