Current advances in the treatment of Alzheimer's disease: focused on considerations targeting Aβ and tau

Abstract

Alzheimer's disease (AD) is a neurodegenerative disorder that impairs mainly the memory and cognitive function in elderly. Extracellular beta amyloid deposition and intracellular tau hyperphosphorylation are the two pathological events that are thought to cause neuronal dysfunction in AD. Since the detailed mechanisms that underlie the pathogenesis of AD are still not clear, the current treatments are those drugs that can alleviate the symptoms of AD patients. Recent studies have indicated that these symptom-reliving drugs also have the ability of regulating amyloid precursor protein processing and tau phosphorylation. Thus the pharmacological mechanism of these drugs may be too simply-evaluated. This review summarizes the current status of AD therapy and some potential preclinical considerations that target beta amyloid and tau protein are also discussed.

Figure 1

The Aβ-targeting strategies based on the Aβ cascade hypothesis. The processing of APP and the production, degradation of Aβ are illustrated and the therapeutic potential of targets are indicated with vertical arrows marked by alphabet: A, α-secretase activators; B, β-secretase inhibitors; C, γ-secretase inhibitors/modulators; D, immunotherapy; E, Aβ-aggregation inhibitors; F, Aβ-degradation activators. Modified and reproduced with permission from Yang et al. (2012) and see reference [2] for further details.