Background: Alzheimer’s disease (AD) as the most common cause of dementia among
older people has aroused the universal concern of the whole world. However, until now there is still
none effective treatments. Consequently, the development of new drugs targeting this complicated
brain disorder is urgent and needs more efforts. In this review, we detailed the current state of
knowledge about new candidate drugs targeting the pathological proteins especially the drugs which
are employed using the combined methods of in vitro and in silico.
Methods: We looked up and reviewed online papers related to the pathogenesis and new drugs
development of AD. Then, articles up to the requirements were respectively analyzed and summaried
to provide the latest knowledge about the pathogenic effect and the new candidate drugs targeting
Aβ and Tau proteins.
Results: New candidate drugs targeting the Aβ include decreasing the production, promoting the
clearence and preventing aggregation. However these drugs have mostly failed in Phase III clinical
trial stage due to the unsuccessful of reversing cognition symptoms. As to tau protein, the prevention
of tau aggregation and propagation is a promising strategy to synthesize/design mechanismbased
drugs against tauopathies. Some candidate drugs are under research. Moreover, because of
the complex pathogenesis of AD, multi-target drugs have also shed light on the treatment of AD.
Conclusion: Given to the consecutive failure of Aβ-directed drugs and the feasibilities of tautargeted
therapy, more and more researchers suggested that the AD treatment should be moved
from Aβ to tau or focused on considering the soluble form of Aβ and tau as a whole. Moreover, the
novel in silico methods also have great potential in drug discovery, drug repositioning, virtual
screening of chemical libraries. No matter how many difficulties and challenges in prevention and
treatment of AD, we firmly believe that the effective and safe drugs will be found using the combined
methods in the immediate future with the global effort.