Alzheimer’s disease (AD)

 Alzheimer’s disease (AD) is a neurodegenerative disorder characterized by a long evolution whose clinical symptoms appear late in life. However, in the last years, the paradigm of AD has changed. In the past, researchers thought AD was an age-related disorder that begins during the aging process. Today we know that the onset of the disease occurs between 15 (for the genetic) and 20–30 years (for the sporadic) before any clinical symptom appears. 

There is no preventive or curative therapy for the disease and the lack of knowledge of when the disease begins greatly complicates the work of the physicians. Another added handicap is that neither do we know why the disease begins. In this sense, there are several hypotheses trying to explain the beginning of AD. These hypotheses may not be exclusive, and they may well overlap and take place at the same time. We can divide the hypotheses into three groups: The hypotheses based on protein deposits. This group includes the beta-amyloid (Aβ) cascade hypothesis; and the tau hypothesis. The deposits mainly formed by Aβ peptide are known as senile plaques. Aβ comes from the proteolysis of a membrane protein called amyloid precursor protein (APP). In favor of the Aβ cascade the theory we can say that mutations in genes involved in the genesis of Aβ cause AD; mutations in the gene encoding the tau protein do not cause amyloid deposition; the ApoE4 allele leads to a reduction in the clearance of the Aβ peptide and increases the risk of AD; Aβ oligomers that are isolated from AD brains involve loss of synapses, neuro.