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

Chris G. Parsons, Gerhard Rammes

Research output: Contribution to journalReview articlepeer-review

26 Scopus citations

Abstract

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-β (Aβ) in the brain. Since current treatment options only provide symptomatic help and Aβ is thought to underlie early synaptic pathology, Aβ 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 Aβ pathophysiology. Data and analysis for this review were procured from PubMed, clinicaltrials.gov and Alzforum. Expert opinion: According to current knowledge, reducing Aβ 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 Aβ oligomerization. Combination approaches targeting both Aβ and tau would seem to be another promising strategy that could have beneficial effects through the course of the disease.

Original languageEnglish
Pages (from-to)579-592
Number of pages14
JournalExpert Opinion on Investigational Drugs
Volume26
Issue number5
DOIs
StatePublished - 4 May 2017
Externally publishedYes

Keywords

  • I
  • PPARγ agonists and secretase inhibitor
  • Phase 0
  • aggregation inhibition
  • amyloid-β
  • and II trials related to AD
  • monoclonal antibodies
  • passive or active immunization

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