Alzheimer's disease - history of failures - a short opinion on the contemporary status of research

Abstract

Over 110 years have passed since first description of Alzheimer's disease (AD). Despite intensive research, AD remains incurable. The vast majority of clinical trials on new therapies aimed at suppressing undesirable aggregation of β-amyloid have failed. This requires rethinking of the strategy to fight AD. A lot of evidence supports the maintenance of β-amyloid as the central object of AD pathology, however, its aggregation into larger supramolecular structures is probably an intermediate stage and not the cause of the disease. In the early stages of life, cellular stresses lead to epigenetic changes resulting in later amyloidogenesis and subsequent neurodegeneration. This process takes decades of life trajectory. Therefore, possible therapies should take into account this fact and be applied early in the life and prolonged later. Diagnosis of epigenetic changes leading to AD should be a research priority. If this concept is true, it may give hope to reverse these changes.