[Development of Disease-modifying Therapy for Alzheimer's Disease]

Abstract

The development of disease-modifying therapy (DMT) that can arrest the pathological processes of Alzheimer's disease (AD) has emerged as one of the highest priorities of medical research. Two pathological hallmarks, amyloid-beta (Abeta) protein deposition and tau accumulation, are the major targets of DMT. Immunotherapy for Abeta removal and secretase inhibitors/modulators that reduce total or accumulation-prone Abeta are candidate DMTs against Abeta. Compounds that prevent tau aggregation are also under development. Clinical trials that test the efficacy of these DMT candidates are in preparation or ongoing. Recent studies of biomarkers of AD brain lesions have indicated that Abeta and tau accumulation appears 10 to 30 years before the occurrence of dementia and gradually propagate to reach the level that causes symptoms. Therefore, efficacy of DMT has to be evaluated in the preclinical stage of AD. The incidence of preclinical AD in the cognitively normal, aged population are estimated to be around 19%. Thus, currently available biomarkers, amyloid/tau PET imaging and cerebrospinal fluid measurements of Abeta and tau, are, perhaps, too invasive and costly. An international collaborative effort is needed to overcome this issue.