Adult human nerve cells contain tau protein, a phosphorylated 
microtubule-associated protein, that is hyperphosphorylated in the fetus and in 
patients with Alzheimer's disease. Hyperphosphorylation, which diminishes the 
microtubule-binding capacity of tau, destabilizes microtubules and may enhance 
the formation of paired helical filaments that constitute neurofibrillary 
tangles in Alzheimer's disease. Here, we use phosphorylation-dependent anti-tau 
antibodies to detect specific epitopes that characterize hyperphosphorylated 
tau. Our demonstration of intracellular tangles containing full-length tau that 
are not immunolabeled by these antibodies suggests that hyperphosphorylation of 
tau is not obligatory in the formation of neurofibrillary tangles in Alzheimer's 
disease.