Recent approaches targeting beta-amyloid for therapeutic intervention of Alzheimer's disease

Alzheimer's disease (AD) is a neurodegenerative disorder characterized by neuropathological features comprising amyloid deposits and neuronal losses in brain. In AD, aggregation of a β amyloid peptide (Aβ), produced from proteolytic cleavage of amyloid precursor protein, is believed to be implicated in the pathophysiological cascade leading to neuronal death. Most AD drugs currently available can only alleviate symptoms rather than modify the underlying molecular cause of AD. In this review, we describe and discuss the recent patents issued within the past two years focusing on therapeutic interventions targeting at various Aβ-associated pathological mechanisms of AD. The described therapeutic strategies include 1) reduction of synthesis of Aβ, 2) inhibition of Aβ aggregation, 3) immunotherapeutic/enzymatic clearance of Aβ, 4) targeting other amyloidogenic proteins interacting with Aβ and 5) amelioration of Aβ downstream toxic effects. Important issues to be considered for further improvement of therapeutic efficacy of these approaches are also discussed.