Treatment of Alzheimer\u2019s disease: symptomatic and disease-modifying approaches

The two major neuropathologic hallmarks of Alzheimer's disease (AD) are extracellular Amyloid \u3b2 (A\u3b2) plaques and intracellular neurofibrillary tangles (NFTs). A number of additional pathogenic mechanisms, possibly overlapping with A\u3b2 plaques and NFTs formation, have been described, including inflammation, oxidative damage, iron disregulation, cholesterol metabolism. The first drugs developed for AD, anticholinesterase inhibitors (AchEI), increase acetylcholine levels, previously demonstrated to be reduced in AD. To date, four AchEI are approved for the treatment of mild to moderate AD. A further therapeutic option available for moderate to severe AD is memantine. These treatments are symptomatic, whereas drugs under development are supposed to modify pathological steps leading to AD, thus acting on the evolution of the disease. For this reason they are currently termed \u201cdisease modifying\u201d drugs. To block the progression of the disease, they have to interfere with pathogenic steps at the basis of clinical symptoms. In this review, current treatment will be summarized and new perspectives discussed. In particular, several approaches will be described, including A\u3b2 deposition interference by Anti-A\u3b2 aggregation agents, vaccination, \u3b2- secretase inhibition or Selective A\u3b242-lowering agents (SALAs); tau deposition interference by methyl thioninium chloride (MTC); reduction of inflammation and oxidative damage