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lüll Disease-modifying treatments for Alzheimer s disease Galimberti D; Scarpini ETher Adv Neurol Disord 2011[Jul]; 4 (4): 203-16The first drugs developed for Alzheimer's disease (AD), acetylcholinesterase 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 intended to modify the pathological steps leading to AD, thus acting on the evolution of the disease. For this reason they are have been termed 'disease-modifying' drugs. To block the progression of the disease they have to interfere with the pathogenic steps responsible for the clinical symptoms, including the deposition of extracellular amyloid beta (Abeta) plaques and of intracellular neurofibrillary tangles, inflammation, oxidative damage, iron deregulation and cholesterol metabolism. In this review, new perspectives will be discussed. In particular, several approaches will be described, including interference with Abeta deposition by anti-Abeta aggregation agents, vaccination, gamma-secretase inhibitors or selective Abeta-lowering agents; interference with tau deposition by methylthioninium chloride; and reduction of inflammation and oxidative damage.ä |