Background: The last two decades have seen a great advance in the data that supports the two
current hypotheses in Alzheimer's disease field, the amyloid beta hypothesis and the tau hypothesis. Not
surprisingly, Aβ and tau proteins are currently the major therapeutic research targets for AD treatment.
Unfortunately, nothing but moderate success has emerged from such therapeutic approaches. With this in
mind, we will discuss deep brain stimulation as a promising therapeutic strategy that aims to restore brain
activity. Lastly, in the scope of cognitive deficit restoration, we will discuss the relevance of the limbic
formation as a promising neuroanatomical target for deep brain stimulation.
Methods: Immunohistochemistry for modified tau (phosphorylated at Ser199–202–Thr205 labelled by
the antibody AT8) was performed on paraffin-embedded human brain sections providing a detailed characterization
of NFT pathology.
Results: Abnormally phosphorylated tau protein is the key common marker in several brain diseases such
as Alzheimer's disease, Parkinson's disease, Pick Disease, Down syndrome and frontotemporal dementia
and is capable of affecting synaptic events that are critical for memory formation. With this in mind,
therapeutic strategies aiming to restore synaptic events could offer better outcomes.
Conclusion: The humble success of current therapeutic strategies along with the lack of basic knowledge
of the brain disease mechanisms calls for alternatives that benefit patients in the present moment. One of
particular interest is the neurostimulation strategy that is already a well-established treatment for several
movement disorders and when compared to current Alzheimer's therapeutic strategies, deep brain stimulation
does not directly interfere with the normal protein function, therefore increasing the probability of