[Therapeutic perspectives in Alzheimer's disease]

Therapeutic perspectives in Alzheimer's disease. Alzheimer's disease (AD) is the most common cause of major neurocognitive disorders, affecting millions of people worldwide and leads to irreversible cognitive decline. The main neuropathological features of AD are the production of abnormal conformational protein (Amyloid Peptide, abnormally phosphorylated tau protein) leading to brain deposits, neuronal and synaptic loss and neurotransmitter deficiency including acetylcholine. The lesions occur 10 to 15 years before the first symptoms. The presence of specific markers in the cerebrospinal fluid is reflecting AD abnormalities (allow determining the presence of these abnormalities in living patients). Currently, only symptomatic treatments (acetylcholinesterase inhibitors and anti-glutamatergics) have been shown to be effective and have been marketed since the late 1990s. Since the early 2000s, therapeutic research has focused on the development of treatments that could modify the evolution of the disease either by increasing the elimination of abnormal proteins, or by decreasing their production and/or their diffusion into the brain. The two current targets are Aβ peptide and the abnormally phosphorylated Tau protein. Regarding the Aβ peptide, the therapeutic trials aimed at increasing its elimination were negative (ineffective) at the stage of major cognitive impairment but give hope for efficacy at the early stage of the disease. Therapeutic trials to reduce its production have been shown to be ineffective or deleterious to patients. Concerning the tau protein, the molecules under development aim at reducing its dissemination in the brain. Altogether, all potential disease modifying treatments are under development.