Alzheimer's

Photobiomodulation is showing to be a promising new treatment strategy for Alzheimer's and other forms of neurodegenerative conditions including amnestic mild cognitive impairment (aMCI). Along with demonstrated clinical effectiveness, it represents a safe, inexpensive, sustainable treatment in both the clinical and at-home setting.

Although Alzheimer's disease is predicted to double in terms of the number of people affected within the next 30 years, we are still yet to find a modality that successfully gives those people their quality of life back. 

After being diagnosed with Alzheimer's, many are not entirely sure what to expect. Alzheimer's is complex and progressive. Sometimes, people may even feel this disease is unbeatable and that their life has reached the end of the road. 

Furthermore, the actual cause of Alzheimer's is still yet to fully be identified. Although some scientists still point to the amyloid and tau deposit hypothesis, many are starting to regard this as a hijacked dogma of the 90s and 2000s.

More and more researchers are stating that the true cause of Alzheimer's disease begins in the gut, and by modulating our gut microbiome, we can even revert this condition. 

Additionally, there is a lack of reliable diagnostic tools that could detect the presence of disease before the onset of symptoms. 

It is safe to say Alzheimer's Disease remains a hot debate. 

The key to a cure for Alzheimer's may still lie in the dark. But, as the literature shows, it is possible to apply technology such as photobiomodulation to pave the way.

Alzheimer's Picture

PBM has been shown to reduce amyloid-β aggregates in human neuroblastoma cells (Sommer et al., 2012) and has been observed to minimize Aβ-induced oxidative stress and inflammatory responses in rat primary cortical astrocytes (Yang et al., 2010). Both of these constitute the pivotal pathological drivers seen in AD. 

Furthermore, Song et al., showed that PBM has implications on fundamental neuro inflammatory pathways within human neuronal cells and that PBM can attenuate cell death by reducing microglia-mediated toxicity via the tyrosine-protein kinase Src/Syk signalling pathway (Song, Zhou and Chen, 2012). 

Remarkably, Farfara et al. and Oron et al. used PBM to stimulate the proliferation of mesenchymal stem cells (MSCs), which had the downstream effect of ameliorating AD disease progression in mice. Weekly treatments of PBM forced phagocytosis of Aβ protein within the brain by MSCs, leading to improved cognitive function and spatial learning compared to the sham-treated control group (Farfara et al., 2014). 

Histochemical Evidence: 

  • Two AD-transgenic mouse models were engineered to develop neurofibrillary tangles or Aβ plaques. 
  • Both models were treated 20 times over four weeks with PBM. 
  • Neurofibrillary tangles, hyperphosphorylated tau protein and oxidative stress markers in both cohorts were reduced to near wild-type levels.
  • Additionally, PBM also reduced the number and size of the Aβ plaques (Purushothuman et al., 2014) 

When we bring PBM back to human subjects to support its therapeutic value, a significant improvement in cognitive tests was observed in a placebo-controlled study just after a single session of PBM (Barrett and Gonzalez-Lima, 2013). These included:

  • Improvements in reaction time in a sustained-attention psychomotor vigilance task
  • Match-to-sample memory task
  • Executive function 

Even in case studies where transcranial PBM was used after traumatic brain injury and left hemisphere stroke, patients saw improved cognitive function (Naeser et al., 2011), (Naeser et al., 2020). 

So, has the light dawned on Alzheimer's Disease? Clinical trials have yet to show any real benefit of pharmaceutical drugs in stabilizing or reversing the steady decline in cognitive function. 

When thinking of PBM, you must consider the mitochondria, specifically the terminal enzyme cytochrome C oxidase that inhabits the electron transport chain within its outer membrane.

Cytochrome C oxidase is the key chromatic player amongst our many biological molecules. Throughout many publications, cytochrome C oxidase is regarded as the king photo-acceptor and transducer of signals activated by light in the infrared region.

Cytochrome C oxidase mediates the transfer of electrons from cytochrome C to molecular oxygen. The net result of this electron delivery is the synthesis of adenosine triphosphate (ATP), the universal energy currency. 

Therefore, blasting cytochrome C oxidase with photons of light delivered by PBM technology leads to an increased electron availability, increased mitochondrial membrane potential and an increased level of ATP. All restore mitochondrial function, trigger the initiation of cellular signalling pathways and revive failing neurons.

Fundamentally, PBM is being shown to trigger retrograde mitochondrial signalling (Karu, 2008). The biological absorption of light induced by PBM results in an altered mitochondrial ultrastructure and triggering of mitochondrial biogenesis (Passarella and Karu, 2014). This mechanism alone is one of the pivotal reasons why PBM is thought to reverse cognitive decline. 

The bottom line is that PBM improves metabolic functioning within the brain's neurones due to increased intracellular ATP production.

Additionally, PBM positively impacts cerebral blood flow to the brain, which is one of the most straightforward changes to measure post-PBM session and has been documented throughout the photobiomodulation landscape. 

Nitric oxide (NO) is suggested to be the causative factor for this mechanism due to its ability to trigger vasodilation (Lee et al., 2017). 

Along with improving blood flow to the brain, PBM has also been shown to stimulate an increase in angiogenesis (new blood vessel growth) within the brain, furthering the improvements in cerebral blood supply (Cury et al., 2013). 

PBM has also shown broad neuroprotective effects, essentially preventing damage to the neurone, promoting their survival and longevity, and reversing apoptotic signalling processes. 

Not long ago, the scientific community accepted that the adult brain is incapable of growing new brain cells. Rightly so, this idea was overturned. 

In recent years we have begun to understand that adult neurogenesis is possible through the mechanism of neural stem cells (NSCs) that can generate new neurons, glial cells, or both. 

Within the space of photobiomodulation, the first report of neurogenesis being stimulated by transcranial PBM came from a 2006 study conducted by Oron et al.. Stroke-induced rats were shown to have a significant number of newly formed neuronal cells and migrating cells when treated with PBM (Oron et al., 2006). 

tPBM's ability to promote synaptogenesis, otherwise known as neuroplasticity, is even more notable. Such a process is vitally important in individuals with not just Alzheimer's but also TBI, stroke and mood disorders. 

Many neurodegenerative diseases can be traced back to poor or aberrant neuronal connections in specific brain regions. 

Transcranial PBM is thought to counter incomplete synaptic transmission by facilitating neural organisation and reorganisation. 

tPBM has been shown throughout the literature to up-regulate neurotrophins and nerve growth factors, the most influential being a brain-derived neurotrophic factor (BDNF). BDNF is a protein that maintains the firing and wiring of existing neurones and encourages the growth of new neurons and synapses. 

Meng et al. showed that the neural tissue of embryonic rats after PBM showed denser branching and increased interconnectivity (Meng, He and Xing, 2013). 

Human clinical trials of PBM in Alzheimer's Disease have also shown promising results in terms of quality of life. 

In a case series of five patients diagnosed with mild to moderately severe dementia who received 12 weeks of active PBM, all patients showed: 

  • Significant increase in cognitive function 
  • Improved sleep 
  • Fewer angry outbursts 
  • Less anxiety 
  • Less wandering 

(Saltmarche et al., 2017) 

Dr Marvin Berman, an integral member of Neuronic, carried out his own small pilot double-blind, placebo-controlled trial in subjects diagnosed with dementia. The results showed: 

  • Improvement in executive function 
  • Clock drawing 
  • Immediate recall 
  • Praxis memory 
  • Visual attention 
  • Task switching 
  • Improved EEG amplitude and connectivity measures.

(Berman et al., 2017). 

Conclusion

These findings suggest that PBMT could be the next big thing. Regarding AD, we're still searching for answers, and if PBMT pans out, it could help millions of people worldwide. 

We have shown that PBMT may be a promising new treatment strategy for Alzheimer's Disease (AD) and mild cognitive impairment (MCI). It has the main benefits of being safe, inexpensive, sustainable and measurable in a clinical setting. The effects on the physiology of memory circuits in the hippocampus are attractive to researchers who study AD and MCI. 

Related Research

  • Photobiomodulation for Alzheimer's Disease: Has the Light Dawned? Michael R Hamblin, 2019. [Link]
  • Photobiomodulation with Near Infrared Light Helmet in a Pilot, Placebo Controlled Clinical Trial in Dementia Patients Testing Memory and Cognition Marvin H Berman 1, James P Halper 1, Trent W Nichols 2, H Jarrett 2, Alan Lundy 2, Jason H Huang, 2017. [Link]
  • Turning On Lights to Stop Neurodegeneration: The Potential of Near Infrared Light Therapy in Alzheimer's and Parkinson's Disease Daniel M Johnstone, Cécile Moro, Jonathan Stone, Alim-Louis Benabid, John Mitrofanis,  2016. [Link]
  • Shining light on the head: Photobiomodulation for brain disorders Michael R Hamblin 2016. [Link]
  • Synergistic photobiomodulation with 808-nm and 1064-nm lasers to reduce the β-amyloid neurotoxicity in the in vitro Alzheimer’s disease models Renlong Zhang, Ting Zhou, Soham Samanta, Ziyi Luo, Shaowei Li, Hao Xu and Junle Qu, 2022. [Link]
  • Transcranial Photobiomodulation of Clearance of Beta-Amyloid from the Mouse Brain: Effects on the Meningeal Lymphatic Drainage and Blood Oxygen Saturation of the Brain O. Semyachkina-Glushkovskaya,1 M. Klimova,1 T. Iskra,1 D. Bragin,2 A. Abdurashitov,1 A. Dubrovsky,1 A. Khorovodov,1 A. Terskov,1 I. Blokhina,1 N. Lezhnev,1 V. Vinnik,1 I. Agranovich,1 A. Mamedova,1 A. Shirokov,3 N. Navolokin,4 B. Khlebsov,3 V. Tuchin,1 and J. Kurths1,5,6 2021

 

Neuronic devices are not medical devices ​under any jurisdiction and are not intended to diagnose, treat, cure or prevent any disease. These statements have not been evaluated by the Food and Drug Administration. Neuronic is not providing any medical advice. We advise you to consult a medical professional and conduct your own independent research.

 

 

References

Sommer, A., Bieschke, J., Friedrich, R., Zhu, D., Wanker, E., Fecht, H., Mereles, D. and Hunstein, W., 2012. 670 nm Laser Light and EGCG Complementarily Reduce Amyloid-β Aggregates in Human Neuroblastoma Cells: Basis for Treatment of Alzheimer's Disease?. Photomedicine and Laser Surgery, 30(1), pp.54-60. 

Yang, X., Askarova, S., Sheng, W., Chen, J., Sun, A., Sun, G., Yao, G. and Lee, J., 2010. Low energy laser light (632.8 nm) suppresses amyloid-β peptide induced oxidative and inflammatory responses in astrocytes. Neuroscience, 171(3), pp.859-868. 

Song, S., Zhou, F. and Chen, W., 2012. Low-level laser therapy regulates microglial function through Src-mediated signaling pathways: implications for neurodegenerative diseases. Journal of Neuroinflammation, 9(1). 

Purushothuman, S., Johnstone, D., Nandasena, C., Mitrofanis, J. and Stone, J., 2014. Photobiomodulation with near infrared light mitigates Alzheimer’s disease related pathology in cerebral cortex – evidence from two transgenic mouse models. Alzheimer's Research & Therapy, 6(1), p.2. 

Barrett, D. and Gonzalez-Lima, F., 2013. Transcranial infrared laser stimulation produces beneficial cognitive and emotional effects in humans. Neuroscience, 230, pp.13-23. 

Naeser, M., Saltmarche, A., Krengel, M., Hamblin, M. and Knight, J., 2011. Improved Cognitive Function After Transcranial, Light-Emitting Diode Treatments in Chronic, Traumatic Brain Injury: Two Case Reports. Photomedicine and Laser Surgery, 29(5), pp.351-358. 

Naeser, M., Ho, M., Martin, P., Hamblin, M. and Koo, B., 2020. Increased Functional Connectivity Within Intrinsic Neural Networks in Chronic Stroke Following Treatment with Red/Near-Infrared Transcranial Photobiomodulation: Case Series with Improved Naming in Aphasia. Photobiomodulation, Photomedicine, and Laser Surgery, 38(2), pp.115-131. 

Karu, T., 2008. Mitochondrial Signaling in Mammalian Cells Activated by Red and Near-IR Radiation. Photochemistry and Photobiology, 84(5), pp.1091-1099. 

Passarella, S. and Karu, T., 2014. Absorption of monochromatic and narrow band radiation in the visible and near IR by both mitochondrial and non-mitochondrial 

photoacceptors results in photobiomodulation. Journal of Photochemistry and Photobiology B: Biology, 140, pp.344-358. 

Lee, H., Lee, S., Kim, S., Kim, N., Park, K., Choi, B., Shin, Y. and Shin, H., 2017. Pretreatment with light-emitting diode therapy reduces ischemic brain injury in mice through endothelial nitric oxide synthase-dependent mechanisms. Biochemical and Biophysical Research Communications, 486(4), pp.945-950. 

Cury, V., Moretti, A., Assis, L., Bossini, P., de Souza Crusca, J., Neto, C., Fangel, R., de Souza, H., Hamblin, M. and Parizotto, N., 2013. Low level laser therapy increases angiogenesis in a model of ischemic skin flap in rats mediated by VEGF, HIF-1α and MMP-2. Journal of Photochemistry and Photobiology B: Biology, 125, pp.164-170. 

Oron, A., Oron, U., Chen, J., Eilam, A., Zhang, C., Sadeh, M., Lampl, Y., Streeter, J., DeTaboada, L. and Chopp, M., 2006. Low-Level Laser Therapy Applied Transcranially to Rats After Induction of Stroke Significantly Reduces Long-Term Neurological Deficits. Stroke, 37(10), pp.2620-2624. 

Meng, C., He, Z. and Xing, D., 2013. Low-Level Laser Therapy Rescues Dendrite Atrophy via Upregulating BDNF Expression: Implications for Alzheimer's Disease. Journal of Neuroscience, 33(33), pp.13505-13517. 

Saltmarche, A., Naeser, M., Ho, K., Hamblin, M. and Lim, L., 2017. Significant Improvement in Cognition in Mild to Moderately Severe Dementia Cases Treated with Transcranial Plus Intranasal Photobiomodulation: Case Series Report. Photomedicine and Laser Surgery, 35(8), pp.432-441. 

Berman, M., Halper, J., Nichols, T., H, J., Lundy, A. and Huang, J., 2017. Photobiomodulation with Near Infrared Light Helmet in a Pilot, Placebo Controlled Clinical Trial in Dementia Patients Testing Memory and Cognition. Journal of Neurology and Neuroscience, 08(01).