TY - JOUR
T1 - Treatment of alzheimer's disease
T2 - Symptomatic and disease-modifying approaches
AU - Galimberti, Daniela
AU - Scarpini, Elio
PY - 2010
Y1 - 2010
N2 - The two major neuropathologic hallmarks of Alzheimer's disease (AD) are extracellular Amyloid β(Aβ) plaques and intracellular neurofibrillary tangles (NFTs). A number of additional pathogenic mechanisms, possibly overlapping with Aβ 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 "disease modifying" 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 Aβ deposition interference by Anti-Aβ aggregation agents, vaccination, γ- secretase inhibition or Selective Aβ42-lowering agents (SALAs); tau deposition interference by methyl thioninium chloride (MTC); reduction of inflammation and oxidative damage.
AB - The two major neuropathologic hallmarks of Alzheimer's disease (AD) are extracellular Amyloid β(Aβ) plaques and intracellular neurofibrillary tangles (NFTs). A number of additional pathogenic mechanisms, possibly overlapping with Aβ 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 "disease modifying" 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 Aβ deposition interference by Anti-Aβ aggregation agents, vaccination, γ- secretase inhibition or Selective Aβ42-lowering agents (SALAs); tau deposition interference by methyl thioninium chloride (MTC); reduction of inflammation and oxidative damage.
KW - Alzheimer's disease
KW - Amyloid
KW - Disease-modifying drugs
KW - Inflammation
KW - Tau
UR - http://www.scopus.com/inward/record.url?scp=77953778864&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=77953778864&partnerID=8YFLogxK
U2 - 10.2174/1874609811003010046
DO - 10.2174/1874609811003010046
M3 - Article
C2 - 20298170
AN - SCOPUS:77953778864
VL - 3
SP - 46
EP - 56
JO - Current Aging Science
JF - Current Aging Science
SN - 1874-6128
IS - 1
ER -