Tau, Amyloid Beta and Deep Brain Stimulation: Aiming to Restore Cognitive Deficit in Alzheimer's Disease

Topic: Brain proteins, microglia and lab models

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 success.

Key findings

• 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.
• 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 success.

Why it matters

This paper discusses deep brain stimulation as a possible strategy to restore brain activity and cognitive function, noting that amyloid and tau-targeted therapies have shown only moderate success. It is a discussion of a potential approach, not a completed trial showing that deep brain stimulation treats or prevents Alzheimer's disease.

Study details

• Evidence strengthLow

Read the original

• DOI: 10.2174/1567205013666160819131336
• PubMed: 27539594
• Original source →

May need a subscription OpenAlex found no free copy of the full text (checked 6 Feb 1020), so the publisher may charge for it. The PubMed abstract is free.

@article{mondragonrodriguez2017-27539594,
  author  = {Mondragón-Rodríguez, S. and Perry, G. and Pena-Ortega, F. and Williams, S.},
  title   = {{Tau, Amyloid Beta and Deep Brain Stimulation: Aiming to Restore Cognitive Deficit in Alzheimer's Disease}},
  journal = {Current Alzheimer research},
  year    = {2017},
  doi     = {10.2174/1567205013666160819131336},
  pmid    = {27539594},
  url     = {https://doi.org/10.2174/1567205013666160819131336}
}

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