What do we do?

Electrical stimulation of glia cells in the brain

– 1 –
Development and validation of electrical stimulation protocols using our proprietary NENI® technology platform.

– 2 –
Acquisition of patient’s data (amyloid PET and tau PET) to identify regions of interest for electrical stimulation.

– 3 –
Personalization step: Computer simulation of different electrode montages to optimize the stimulations of the affected regions.

– 4 –
Delivery of non-invasive 30 min therapy sessions for 6+ months using a tCS headset with a follow-up PET scan.

Molecular and cellular changes in the brain of AD patients

amyloid plaques, neurofibrillary tangles, chronic inflammation

The main characteristics can be named as formation of amyloid plaques, neurofibrillary tangles, chronic inflammation and following neuronal death and brain atrophy (shrinkage).

Amyloid β plaques: Proteolytic cleavage of the Amyloid β-protein precursor leads to Amyloid β40 and Amyloid β42 peptides which are the main component of the amyloid plaques. In the healthy brain these peptides are degraded rapidly and do not aggregate. However, different causes can lead to an increased amount and accumulation of Amyloid-β40/42 in the brain. For example, mutations in the Amyloid β-protein precursor gene, changes in the proteases or increased production of Amyloid β-protein precursor.

Neurofibrillary tangles: Neurofibrillary tangles are abnormal accumulations of the hyperphosphorylated tau-protein in neurons. In healthy neurons the tau protein stabilizes microtubules which help to guide nutrients and molecules from the cells body to the axon and dendrites. However, in Alzheimer’s Disease these tau hyperphosphorylation leads to aggregation and forming of threads followed neurofibrillary tangles. These tangles block the transport system within neurons and therefor harm synaptic communication and lead to neuronal death.

Neuroinflammation: The immune cells of the central nervous system, the microglia normally engulf and destroys waste and toxins in the brain. However, they do fail to engulf and degrade amyloid-β plaques. Together with astrocytes, another type of glia cells they assemble around the amyloid-β plaques and release pro-inflammatory cytokines which causes a chronic inflammation and damage the neurons they should protect.

References

Electrical stimulation, microglia, Alzheimer's Disease

  1. What Happens to the Brain in Alzheimer’s Disease? | National Institute on Aging.
    Available at: https://www.nia.nih.gov/health/what-happens-brain-alzheimers-disease. (Accessed: 21st May 2021)
  2. Lee, J. et al. 40 Hz acoustic stimulation decreases amyloid beta and modulates brain rhythms in a mouse model of Alzheimer’s disease. bioRxiv (2018). https://www.biorxiv.org/content/10.1101/390302v1 
  3. Iaccarino, H. F. et al. Gamma frequency entrainment attenuates amyloid load and modifies microglia. Nature 540, 230–235 (2016). https://www.nature.com/articles/nature20587 
  4. A.J., M. et al. Multi-sensory Gamma Stimulation Ameliorates Alzheimer’s-Associated Pathology and Improves Cognition. Cell (2019).
    https://www.sciencedirect.com/science/article/pii/S0092867419301631
  5. Clements-Cortes, A., Ahonen, H., Evans, M., Freedman, M. & Bartel, L. Short-Term Effects of Rhythmic Sensory Stimulation in Alzheimer’s Disease: An Exploratory Pilot Study. J. Alzheimer’s Dis. (2016). https://pubmed.ncbi.nlm.nih.gov/27031491/
  6. Multi-Center Study of Sensory Stimulation to Improve Brain Function – Full Text View – ClinicalTrials.gov.
    Available at: https://clinicaltrials.gov/ct2/show/NCT03556280. (Accessed: 21st May 2021)