Methylation and Phosphorylation: A Tangled Relationship? Many

neurodegenerative diseases are associated with distinctive brain lesions. One particular group of hetero-geneous dementias and movement disorders is character-ized by intracellular accumulations of abnormal filaments called neurofibrillary tangles (NFT), formed by the micro-tubule-associated protein tau. These neurodegenerative tauopathies include Pick disease and Alzheimer disease (AD), but the term also encompasses a range of other clinical conditions that share a common end-point: neu-rodegeneration with pathological tau accumulation (1). Tau occurs predominantly in neuronal axons, where it binds to microtubules and regulates their length and “treadmilling ” dynamics. Tight regulation of microtubule activity is critical to cell viability, and fine regulation of tau is likely to be equally important (2)