Preclinical to phase II amyloid beta (A) peptide modulators under investigation for Alzheimer's disease

Introduction: Alzheimer disease (AD) is the most common form of dementia and its incidence is increasing at an alarming rate all over the world. The pathophysiology of AD is characterized by chronic, progressive neurodegeneration which involves early synaptotoxicity. One of the most obvious pathological feature of AD is the accumulation of amyloid- (A) in the brain. Since current treatment options only provide symptomatic help and A is thought to underlie early synaptic pathology, A reduction or modulation in the brain may be a promising therapeutic strategy in preventing and /or reversing AD-related dysfunction.Areas covered: This paper outlines and evaluates the current landscape of preclinical and clinical studies focusing on modulating A pathophysiology. Data and analysis for this review were procured from PubMed, clinicaltrials.gov and Alzforum.Expert opinion: According to current knowledge, reducing A production offers numerous treatment options. However, targeting the initial steps by pharmacological interference with secretases is challenging due to the emergence of various side effects. The most promising approach seems to be the prevention of early A oligomerization. Combination approaches targeting both A and tau would seem to be another promising strategy that could have beneficial effects through the course of the disease.