Alzheimer's disease: From pathogenesis to novel therapeutic approaches

The two major neuropathologic hallmarks of Alzheimer's disease are extracellular amyloid β (Aβ) plaques and intracellular neurofibrillary tangles. Several additional pathogenic mechanisms have been described, including inflammation, oxidative damage, ion disregulation and cholesterol metabolism. A number of compounds have been developed, trying to interfere with the above-mentioned mechanisms. These drugs are supposed to modify pathological steps leading to Alzheimer's disease, thus acting on the evolution of the disease. Some of these compounds are under clinical testing, others are in preclinical phases of development. In this review, the main pathogenic steps leading to neurodegeneration will be discussed, together with an update on potentially disease-modifying drugs under testing.