EXAMINATION OF PHOSPHORYLATED TAN PROTEIN AS A PHF-PRECURSOR AT EARLY-STAGE ALZHEIMERS-DISEASE

Hyperphosphorylated tau protein which can be isolated on the basis of insolubility in 1% sarkosyl (A68-tau fraction) is thought to represent a precursor pool for PHF assembly, associated histologically with neu ritic pathology, which feeds into a more resistant tangle-associated P HF pool via cross-linking and proteolysis. We examined these predictio ns at the earliest detectable stages of neurofibrillary pathology. We report that there is no evidence that neuritic pathology represents an early pathologic stage, no evidence of an association between neuriti c pathology and phosphorylated tau, no evidence of selective accumulat ion of phosphorylated tan at early stages of pathology, and no evidenc e for a precursor/product relationship between phosphorylated tau and PHFs during progression of pathology. We conclude that altered phospho rylation is a secondary process affecting 5% of PHFs and does not expl ain PHF assembly in Alzheimer's disease.