TY - JOUR
T1 - Amyloid-modifying therapies for Alzheimer's disease
T2 - Therapeutic progress and its implications
AU - Creed, Meaghan C.
AU - Milgram, Norton W.
PY - 2010/9
Y1 - 2010/9
N2 - Alzheimer's disease (AD) is the most prevalent form of dementia, affecting an estimated 4.8 million people in North America. For the past decade, the amyloid cascade hypothesis has dominated the field of AD research. This theory posits that the deposition of amyloid-beta protein (Aβ) in the brain is the key pathologic event in AD, which induces a series of neuropathological changes that manifest as cognitive decline and eventual dementia. Based on this theory, interventions that reduce Aβ burden in the brain would be expected to alleviate both the neuropathological changes and dementia, which characterize AD. Several diverse pharmacological strategies have been developed to accomplish this. These include inhibiting the formation of Aβ, preventing the aggregation of Aβ into insoluble aggregates, preventing the entry of Aβ into the brain from the periphery and enhancing the clearance of Aβ from the central nervous system. To date, no amyloid-modifying therapy has yet been successful in phase 3 clinical trials; however, several trials are currently underway. This article provides a review of the status of amyloid-modifying therapies and the implications for the amyloid cascade hypothesis.
AB - Alzheimer's disease (AD) is the most prevalent form of dementia, affecting an estimated 4.8 million people in North America. For the past decade, the amyloid cascade hypothesis has dominated the field of AD research. This theory posits that the deposition of amyloid-beta protein (Aβ) in the brain is the key pathologic event in AD, which induces a series of neuropathological changes that manifest as cognitive decline and eventual dementia. Based on this theory, interventions that reduce Aβ burden in the brain would be expected to alleviate both the neuropathological changes and dementia, which characterize AD. Several diverse pharmacological strategies have been developed to accomplish this. These include inhibiting the formation of Aβ, preventing the aggregation of Aβ into insoluble aggregates, preventing the entry of Aβ into the brain from the periphery and enhancing the clearance of Aβ from the central nervous system. To date, no amyloid-modifying therapy has yet been successful in phase 3 clinical trials; however, several trials are currently underway. This article provides a review of the status of amyloid-modifying therapies and the implications for the amyloid cascade hypothesis.
KW - Alzheimer's disease
KW - Amyloid cascade hypothesis
KW - Beta-amyloid
KW - Cognition
KW - Secretase
KW - Vaccination
UR - http://www.scopus.com/inward/record.url?scp=77956182735&partnerID=8YFLogxK
U2 - 10.1007/s11357-010-9142-z
DO - 10.1007/s11357-010-9142-z
M3 - Review article
C2 - 20640545
AN - SCOPUS:77956182735
SN - 0161-9152
VL - 32
SP - 365
EP - 384
JO - Age
JF - Age
IS - 3
ER -