Tau therapeutics for alzheimer’s disease

Abstract

The pathological diagnosis of Alzheimer’s disease (AD) depends on the presence of plaques consisting of the β-amyloid peptide as well as neurofibrillary tangles consisting of paired helical filaments (PHFs) of the tau (τ) protein. The role of each type of pathology in the pathogenesis and progression of AD remains unclear. Previous hypotheses suggested that these two processes were independent, whereas more recent data suggest that there may be a bidirectional interaction between these two pathological processes.

The identification of the neurotoxic effects of β-amyloid and the discovery of mutations responsible for earlyonset Alzheimer’s disease (EOAD) and their linkage to β-amyloid overproduction, has made the amyloid hypothesis of AD the predominant influence for therapeutic targets. Several approaches have emerged from preclinical testing and have entered early phases of clinical developments.

The recent identification of τ mutations and their linkage to progressive neurodegenerative disorders provides a counterbalancing influence on the search for therapeutic targets for AD. Therapeutic approaches that are targeted to either β-amyloid or τ share certain features at the level of pharmacology and will face many of the same challenges as they progress through drug development paradigms. The aim of this article is to provide a brief overview of some of the commonalities and the challenges faced by τ-related therapeutic strategies. The issues discussed in this article are not exhaustively dealt with in either scope or detail.