Alzheimers disease (AD) is the leading cause of dementia in elderly people. It is a progressive, degenerative and irreversible brain disorder causing cognitive impairment, confusion, disorientation, personality and behavior change, and eventually death. It is characterized by three main stages of progression: mild, moderate and severe. The prevalence rate of Alzheimers disease is estimated at 26 million people worldwide (status 2007). No other risk factor than age is currently known and scientifically confirmed, so that with a growing elderly population the number of affected people increases steadily. Consequently, the prevalence rate of AD is expected to quadruple by 2050.
As AD is a highly care intensive disease, it has a huge economic and social impact. The average annual costs to third-party payers are currently estimated to be about $ 21K per patient or five-fold higher as compared to healthy groups.
While the underlying molecular mechanisms are poorly understood, AD is pathologically defined by massive loss of neurons and the appearance of two kinds of protein aggregates in the brains of patients, neurofibrillary tangles and senile plaques. The major constituents of neurofibrillary tangles are aberrantly cleaved and phosphorylated versions of Tau, a protein, which normally is required for the maintenance of proper neuronal architecture. Senile plaques consist of aggregated, highly neurotoxic Amyloid beta peptides (Abeta or Aβ), which are generated from a precursor protein, APP, through proteolytic cleavage by a variety of enzymes. The normal function of APP is, however, not yet fully understood.
While Abeta and Tau are also the major drivers of academic research directed at the elucidation of the underlying molecular defects causing the disease, the inhibition of the production of Abeta or the aberrant phosphorylation of Tau are in the focus of most AD drug discovery programs pharmaceutical and biotechnology companies.