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Plasmon hope
Plasmon hope Plasmon hope

A group of Taiwanese scientists have developed an innovative approach in the treatment of Alzheimer’s disease, an irreversible and still incurable progressive neurodegenerative disorder that slowly destroys memory and cognitive function in the brain. In a 3-month experiment, mice were given a daily intake of plasmon-activated water, which increasingly improved their memory. The figure above outlines the test conducted by the scientists (recognition of new objects) and the prevailing results. In the murine Alzheimer’s model, the mice not only ceased to remember previously seen objects, but also exhibited a gradual decrease in the ability to recognize new objects.


However, when ordinary water was replaced with plasmon-activated water, the mice’s test scores improved. In other words, the mice demonstrated a curiosity in new objects much the same as healthy animals do, including giving less of their attention to the old objects. Source - [6].


Thanks to higher standards of living and groundbreaking medical advancements over the years, many countries have seen a significant increase in life expectancy. Nevertheless, longevity with all its benefits also has its drawbacks with age-related diseases such as dementia.


Dementia (from Latin dementia literally “being out of one’s mind”) is a progressive decline in cognitive functions (attention, memory, intelligence) to which there is no known cure. Dementia is a syndrome, not a disease. A syndrome is a group of symptoms that does not have a definitive diagnosis and Alzheimer’s disease (AD) remains the most common symptom of dementia. A person with early stage AD gradually, yet inevitably loses memory. As the disease progresses the patient becomes more disoriented and judgment is impaired. Speech patterns become more difficult and the patient starts to lose the ability to care for himself or herself. The emotional and financial burden on societies is enormous in developed counties like the US, for example, where one out of every 10 people over the age of 65 and 3 out of every 10 people over the age of 85 suffer from the disease. Further compounding the problem is that the disease is irreversible and scientists do not fully understand the nature of the disease. Despite extensive as well as intensive research by many leading laboratories throughout the world, a drug that inhibits the development of AD, or at minimum, induces long-term remission of the disease has yet to be invented [1, 3-5]. New methods and approaches in the treatment of AD are urgently needed as a result.


Although the real causes of AD remain unclear, scientists are certain other types of dementia have a specific neuropathological profile, e.g., extracellular deposition of beta-amyloid peptides (Aβ) spherical in shape (senile plaques) and the presence of intracellular neurofibrillary tangles, consisting of an aggregated hyperphosphorylated protein tau [1]. Therefore, it is believed that Aβ and tau play an important role in the pathogenesis of AD. Aβ, which consists of 40 to 42 amino acids, is formed by sequential cleavage of the amyloid precursor protein transmembrane protein (APP, amyloid precursor protein) with β- and γ-secretase enzymes. Such peptide fragments are formed naturally, however, further pathological testing shows the fragments significantly increase their concentration and begin to polymerize and acquire neurotoxic properties over time. This leads to the death of neurons in the hippocampus and neocortex, the brain structures responsible for cognitive function. Aging, oxidative stress and chronic inflammation contribute to the accumulation of amyloid, which begins 10-20 years before the first clinical manifestations of the disease. Moreover, as amyloid accumulates, inflammation in the brain intensifies [1]. The pathology of the tau protein, normally useful, supports the cell structure due to microtubule polymerization. This support, occurring much later, closely correlates with neurodegenerative changes in the brain (disruption of work and loss of connections between neurons, promoting their death), and, consequently, the clinical manifestations of the disease. It is known that mutations of the APP gene, as well as the proteins that are part of the γ-secretase complex (presenilin 1 and 2), lead to the hereditary “family” form of AD, and the accumulation of Aβ contributes to tau pathology, not vice versa [1]. This data, along with well-grounded, corresponding research, notes the key role Aβ plays in the pathogenesis of AD. Many studies have tried to reduce the rate of Aβ formation either by using β- or γ-secretase inhibitors, removing the Aβ altogether using specific antibodies or enhancing the function of Aβ degradation enzymes [1, 6]. However, none of these methods has been successful so far [1, 3-5]. This indicates the complex nature of the disease, where Aβ, although important, is not the only contributing factor.


In another study, a group of Taipei Medical University scientists has developed a new, unconventional method aimed at slowing the progression of asthma by consuming plasmon-activated water daily instead of ordinary water. Research published in Scientific Research (Nature Publishing group), one of the largest scientific journals available, showed the many advantages plasmon-activated water had over ordinary water. Plasmon Activated Water (PAW) is created by combining ordinary deionized water with gold nanoparticles (au) under a green light emitting diode. Surface plasmon resonance appears on the illuminated Au nanoparticles, which, in turn, contributes to the destruction of hydrogen bonds in the illuminated Au / water [7–8]. The water’s transformation contains properties that are different from ordinary water, e.g., higher vapor pressure, lower specific heat, and an increased ability to dissolve [7–9], subsequently increasing its reactivity.


From a biomedical point of view, the most interesting properties of PAW are antioxidant and anti-inflammatory. It was found that PAW had the ability to absorb free radicals (e.g., hydroxyl and diphenyl picrylhydrazyl), effectively reduce the release of nitric oxide (NO) from lipopolysaccharide-activated cells of the immune system [6,7], and increase levels of Nrf2 an “antioxidant” gene[ 10]. The anti-inflammatory effects of daily PAW use have been demonstrated in animals with various diseases, including chronic renal failure [11, 12], sleep deprivation [13], and lung cancer [10]. Because the inflammatory process plays such a decidedly negative role in neurodegenerative diseases (including AD) [1], Taiwanese scientists decided to study the effects of PAW on mice in the AD model.


In the BA model, Taiwanese scientists selected a transgenic line of mice with two pathological genes - APP and Presenilin 1, corresponding to the BA model with early onset. Aβ deposits were recorded in animals at 6 months old, with senile plaques overwhelmingly present in the cortex and hippocampus by 9 months old. However, neurofibrillary tau-tangles were practically non-existent. The change of behavior and memory in the APP / PS1 line were also observed for approximately 6 months [14]. The scientists designed the experiment based on these dates. Starting at 5 months of age, APP / PS1 transgenic mice were given normal deionized water or PAW for the ensuing 9 months. The controlled group consisted of healthy, normal mice. A cognitive test for memory loss was performed every three months, and after 9 months, positron emission tomography was performed to detect amyloidosis, as well as biochemical studies to determine the level of proteins involved in the development of pathology [6].


To evaluate memory loss, the main clinical symptom of AD, scientists simply tested the mice’s ability to recognize new objects. Generally, as a rule, healthy mice spend much more time with new objects than old as new objects are more attractive to rodents and tend to peak their curiosity. Initially, two identical objects were shown to the mice. The following day, one object was replaced with a new one. The scientists then compared the time the mice spent with the new object to the time spent with the old, familiar object. In mice with an experimental form of AD (APP / PS1 line), their ability to distinguish old objects from new gradually decreased over a 14 month time period, to the point where the mice could barely distinguish one object from the other. Conversely, when APP / PS1 mice received PAW instead of ordinary water, the mice began to distinguish old objects from new after 3 months of therapy.


Accordingly, PET analysis (a standard radioactive label binding to amyloid plaques (18F-Florbetapir) [15] showed significantly lower levels of Aβ in the hippocampus, cortex and hypothalamus in mice administered PAW, although in general, the level of amyloid ingested was still above the controlled group.


Despite these findings, the scientists determined a more comprehensive analysis of the level of Aβ through biochemical studies was in order. Consequently, an enzyme-linked immunosorbent assay was performed to detect the presence of oligomeric forms of Aβ. The scientists also stained sections of the brain in the animals [16] and further investigated the pathology of the tau protein. In transgenic mice, the number of amyloid plaques and the level of p-tau (an indicator of tau pathology) were significantly higher compared to the healthy animals. However, in animals treated with PAW, the level of p-tau in the hippocampus (not the cortex) was significantly lower. Other indicators, such as the level of oligomeric forms of Aβ, interleukins 6 and 1β (inflammation indicators), APP, presenilin 1 and BACE1 proteins involved in the synthesis of Aβ, and neprilysin, an enzyme that destroys Aβ, did not change.


It was concluded that using PAW instead of ordinary water led to a decrease in the amyloid load and the amount of p-tau, as well as improved memory in animals with experimental AD. Concurrently, the level of proteins involved in the metabolism of Aβ and oligomeric Aβ did not change. Furthermore, the research suggests that PAW most likely does not affect the synthesis / degradation of Aβ, but presumably prevents its aggregation and/or has another protective effect, due to its anti-inflammatory characteristics. It remains to be seen whether the same characteristics in PAW that prevent or slow the progression of Aβ in mice will work for asthma as well.


While the data obtained are encouraging, scientists are hesitant to draw definite conclusions due to the small number of animals used in the experimental groups, the authors noted. However, experiments continue, and there is talk in the scientific community about possibly using plasmon-activated water in clinical trials to prevent the progression of Alzheimer's disease in the future.


References


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2.    2019 Alzheimer's Disease Facts and Figures Report

3.    Another Alzheimer's drug flops in pivotal clinical trial

4.    End of the EXPEDITION: Solanezumab Results Published

5.    Biogen/Eisai Halt Phase 3 Aducanumab Trials

6.    Cheng CH, Lin KJ, Hong CT, Wu D, Chang HM, Liu CH, Hsiao IT, Yang CP, Liu YC, Hu CJ. (2019). Plasmon-Activated Water Reduces Amyloid Burden and Improves Memory in Animals with Alzheimer's Disease. Scientific Reports. 9(1): 13252

7.    Chen HC, Hwang BJ, Mai FD, Liu YC, Lin CM, Kuo HS,Chou DS, Lee MJ, Yang KH, Yu CC, Chen JR, Lo TY, Tsai HY, Yang CP, Wang C, Hsieh HT, Rick J. (2014). Active and Stable Liquid Water Innovatively Prepared Using Resonantly Illuminated Gold Nanoparticles. ACS Nano. (8): 2704-2713.

8.    Chen HC, Mai FD, Hwang BJ, Lee MJ, Chen CH, Wang SH, Tsai HY, Yang CP, Liu YC. (2016). Creation of Electron-doping Liquid Water with Reduced Hydrogen Bonds. Scientific Reports. (6):22166-22166.

9.    Yang, C.P., Hong, C.T., Mai, F.D., Tsai, H.Y., Liu, Y.C. (2019). Increasing electrochemical reaction rates using treated water with reduced hydrogen bonds. Journal of Electroanalytical Chemistry, 839, 116-122.

10.    Wang, CK., Chen, HC., Fang, SU., Ho, CW., Tai, CJ., Yang, CP., Liu, YC. (2018). Innovatively Therapeutic Strategy on Lung Cancer by Daily Drinking Antioxidative Plasmon-Induced Activated Water. Scientific Reports, 8(1), 6316.

11.    Chen, H.C.; Lin, H.C.; Chen, H.H.; Mai, F.D.; Liu, Y.C.; Lin, C.M.; Chang, C.C.; Tsai, H.Y.; Yang, C.P. (2014). Innovative strategy with potential to increase hemodialysis efficiency and safety. Scientific Reports. 4, 4425.

12.    Chen, H.C.; Cheng, C.Y.; Lin, H.C.; Chen, H.H.; Chen, C.H.; Yang, C.P.; Yang, K.H.; Lin, C.M.; Lin, T.Y.; Shih, C.M.; et al. (2016). Multifunctions of excited gold nanoparticles decorated artificial kidney with efficient hemodialysis and therapeutic potential. ACS Appl. Mater. Interfaces. 8, 19691–19700.

13.    Chen HC, Cheng CY, Chen LY, Chang CC, Yang CP, Mai FD, Liao WC, Chang HM, Liu YC. (2018). Plasmon-activated water effectively relieves hepatic oxidative damage resulted from chronic sleep deprivation. RSC Advances. 8 (18): 9618-9626.

14.    APPswe/PSEN1dE9 (line 85)
APP mouse models for Alzheimer’s disease preclinical studies

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