1. An 80-year-old woman dies after a long history of progressive memory loss, apraxia, and recurrent episodes of confusion. In the last months of life she was bedridden and unable to recognize familiar faces and objects. The pathologist identifies numerous flame-shaped intracytoplasmic inclusions in neurons of the neocortex and hippocampus. These consist of paired helical filaments (PHFs) on electron microscopy. Which of the following biochemical changes most likely accounts for the development of PHFs in this condition?