[Recent progress in the development of disease-modifying therapies for Alzheimer's disease]

Abstract

Alzheimer's disease (AD) is a neurodegenerative disorder characterized by senile plaques and neurofibrillary tangles in the brain. Currently available therapies for AD may slow cognitive decline but do not alter underlying disease processes. Amyloid beta protein (Abeta), the major component of senile plaques, is a 40 to 43 amino acid peptide cleaved from amyloid precursor protein (APP) by beta-secretase and gamma-secretase and has been implicated as the primary cause of AD. According to the amyloid hypothesis, extensive efforts have been made to find drugs that can reduce brain Abeta accumulation, including prevention of Abeta aggregation, inhibition of APP processing and acceleration of Abeta degradation. Anti-Abeta immunotherapy has attracted considerable attention as the most exciting treatment approach for AD over the last decade, but some patients showed no clinical improvement despite clear reductions of Abeta. More recently, alternative approaches have begun to target the microtubule binding protein tau, a component of neurofibrillay tangles. The combination of therapies against Abeta and tau may be a promising therapeutic strategy for AD.