The Recent Updates of Therapeutic Approaches Against Aβ for the Treatment of Alzheimer's Disease

One of the main neuropathological lesions observed in brain autopsy of Alzheimer's disease (AD) patients is the extracellular senile plaques mainly composed of amyloid-beta (A beta) peptide. Recently, treatment strategies have focused on modifying the formation, clearance, and accumulation of this potentially neurotoxic peptide. beta- and gamma-secretase are responsible for the cleavage of amyloid precursor protein (APP) and the generation of A beta peptide. Treatments targeting these two critical secretases may therefore reduce A beta peptide levels and positive impact on AD. Vaccination is also an advanced approach against A beta. This review focuses on recent advances of our understanding of this key peptide, with emphasis on A beta peptide synthesis, accumulation and neurotoxicity, and current therapies including vaccination and two critical secretase inhibitors. MicroRNAs (miRNAs) are a class of conserved endogenous small noncoding RNAs, known to regulate the expression of complementary messenger RNAs, involved in AD development. We therefore address the relationship of miRNAs in the brain and A beta generation, as a novel therapeutic approach to the treatment of AD while also providing new insights on the etiology of this neurological disorder. Anat Rec, 294: 1307-1318, 2011. (C) 2011 Wiley-Liss, Inc.