Chapter 3 - Tau proteins and their significance in the pathobiology of Alzheimer's disease

Abstract

This chapter discusses tau proteins and their significance in the pathobiology of Alzheimer's disease (AD). Paired helical filaments are found aggregated together into neurofibrillary tangles (NFTs) in the perikarya of selectively vulnerable populations of neurons in AD. It is suggested that the accumulation of neurofibrillary lesions in AD may be caused by the aberrant reactivation of fetal protein kinases and the inactivation of fetal protein phosphatases in the AD brain. The absence of any AD lesions in the fetal central nervous system suggests that these kinases and phosphatases, which are normally present and activated in the fetal nervous system, determine the phosphorylation state of fetal τ but do not generate derivatized forms of that are fully equivalent to paired helical filaments Tau (PHFτ) in the AD brain. It is suggested that some of the differences previously noted between normal adult CNSτ and PHFτ that were obtained from studies of postmortem brain samples may reflect the more rapid dephosphorylation of normal τ versus PHFτ during similar intervals between the death of the patient and the extraction of each of these species of τ protein.