Biomarkers for Alzheimer’s disease: from pathogenesis to drug development

Excerpt

At present, five drugs have been approved for the treatment of Alzheimer’s disease (AD), including four cholinesterase inhibitors (tacrine, donepezil, rivastigmine, and galantamine) and one N-methyl-d-aspartate receptor (NMDAR) antagonist memantine. However, no new drugs for AD have been approved since 2003. According to the Cleveland Clinical study, 99.6% of clinical trials of AD candidate drugs between 2002 and 2012 were failures. The majority of these candidate drugs were symptomatic agents aimed at improving cognition (36.6%), followed by disease-modifying small molecules (35.1%) and disease-modifying immunotherapies (18%) [1]. Many trials fail because the candidates are unable to show a drug/placebo difference or have unacceptable toxicity [1]. The reasons for the lack of efficacy of these AD candidates should be evaluated to improve the success rate for future drug development. More precise understanding of the complex pathogenesis of AD may provide new approaches to novel AD drugs. Furthermore, development of novel AD biomarkers may improve early diagnosis in routine clinical practice and research. …