Alzheimer's disease: a general introduction and pathomechanism

Alzheimer's disease (AD) is the most common form of dementia, which affects more than 35 million people worldwide with increasing tendency. Satisfying therapies and prevention are not available. Since the first description of the fatal progressive neurodegenerative disease in 1907, however, major findings on the molecular mechanisms have been reported. Current clinical trials target diverse aspects and principles of AD, such as the generation and aggregation of amyloid-β (Aβ). Extracellular amyloid plaques, predominantly consisting of Aβ, and intracellular neurofibrillar tangles, formed by hyperphosphorylated tau, are the major pathological hallmarks in the brain of AD patients. AD is consequently one of about 40 identified amyloidoses - protein misfolding diseases, which share as their main pathogenic mechanism the aberrant deposition of endogenous proteins as amyloid fibrils. This article aims principally to introduce AD and its identified key players, to summarize classic and recent publications on the complex molecular mechanisms underlying the disease, and to discuss challenges that need to be faced for the development of improved therapeutic strategies.