All posts by helen03pd2014

Does hygiene lead to a higher risk of Alzheimer’s Disease?

As a student who is passionate about studying psychology, I came across an article on the University of Cambridge’s research site that talks about Alzheimer’s disease, which can be defined as “a progressive disease that destroys memory and other important mental functions”. The article, titled “Better hygiene in wealthy nations may increase Alzheimer’s risk,” argues that there is a strong positive correlation between clean, industrialized countries and the prevalence of Alzheimer’s disease in the countries’ population. (Fox, 2013) While I was initially fascinated by this claim, I knew that I needed to be a little more objective when trusting these relatively one-sided claims. In doing so, then, I formulated the following question: To what extent does hygiene actually contribute to the development of Alzheimer’s disease? In other words, is there a direct cause-effect relationship between cleanliness and Alzheimer’s or is there simply a correlation between the two?

To me, the article seems to suggest that Alzheimer’s Disease (AD) is caused by high sanitation levels within a country because of limited contact with certain bacteria, viruses, and other microorganisms. Deficiency of contact with these microorganisms, they claim, can lead to an insufficient amount of T-cells, which are a form of white blood cells that effectively counteract “foreign substances and disease” (Apple dictionary). The resulting inflammation that occurs from a lack of T-cells is linked to the inflammation that is commonly found in the brains of Alzheimer’s patients. (Better hygiene in wealthy nations may increase Alzheimer’s risk, 2013) So in searching for a clearer answer to my question, I knew that I needed to understand the differences between the brain of an AD patient and a healthy brain, and break them down to their elemental, molecular level to understand exactly what could be the root cause of AD.

The brains of Alzheimer’s patients are characterized by 3 “hallmarks”: an abundance of amyloid plaques, an increase in neurofibrillary tangles, and the destruction of and loss of connection between the nerve cells. (National Institutes of Health, 2011) From this, I thought that perhaps the excess of amyloid plaques could be linked to the lack of T-cells in an Alzheimer’s brain. From here I came across a scientific study that related T-cells to the amyloid-beta proteins (that make up the plaques), and I found that “chronic stimulation by the amyloid-beta protein present in the blood” could be the cause of changes in the T-cells of AD patients that otherwise make us immune to bacteria and other microorganisms. (Mariavaleria et al., 2011) I then came across a second scientific study that claimed that T-cell immunity to bacteria and other microorganisms in AD patients decreased significantly in comparison to the T-cell immunity of healthy patients. (Giubilei et al., 2003) This research seemed to tell me that hygiene may not be the direct cause of AD, but rather that the build-up of amyloid-beta proteins in our brain could be a biological cause.

I followed through with this prediction – that the build-up of amyloid-beta proteins in our body causes AD – by trying to find out where the amyloid-beta protein comes from. Interestingly, I found that there are actually three types of amyloid-beta proteins that are processed from what is called the amyloid precursor protein (APP), which is found widely within the cells of our own bodies. Two types of amyloid-beta proteins (amyloid-beta 38 and amyloid-beta 40) are benign while the third type of amyloid-beta protein (amyloid-beta 42) is toxic and seems to be the one that causes brain damage in AD patients. (Khan) After identifying the type of amyloid-beta protein, then, I came across its chemical structure:

(chemBlink)
(chemBlink)

The molecular formula for amyloid-beta 42 is C203H311N55O60S (chemBlink); clearly, I can see that the molecular structure is quite large. It is also characteristic of a protein, as evidenced by the presence of primary, secondary, and tertiary amides that are part of the molecule. I found that this protein may actually be responsible for damaging the blood-brain barrier by making it more permeable. (Sharma et al., 2012)

From this, I thought that maybe the increase in permeability of the BBB could be linked to a less immune brain, which could connect back to the “hygiene hypothesis.” So I then decided to go back to investigating the immune system’s role in AD pathology by connecting it to its relation with the amyloid-beta 42. I found that the amyloid-beta 42 activates the production of one type of T-cells that “secrete pro-inflammatory cytokines, which cross the BBB and directly activate microglia and astrocytes in the brain, as well as indirectly induce inflammation by activating dendritic cells.” (Town et al., 2005 as cited in Fox et al., 2013) Microglia and astrocytes are “cellular components of the brain’s immune network” (Cohen, 2009); hence, I observe that T-cells modify the performance of these components in the immune system, which fosters the development of AD.

So in answering my question, I find that the amyloid-beta protein and the immune system of the brain are bidirectional in developing AD, and both play significant roles in the pathology of AD. That means that our immune system’s response to different levels of hygiene, along with our genetic predisposition (the presence of APP) both can contribute to increase risk in Alzheimer’s disease.

What are the implications, then, of my findings about AD? Well, since AD is the 5th leading cause of death for those aged 65 and older (Alzheimer’s Association, 2013), understanding the causes of AD can help us better find cures for this disease, which are not entirely ready as of yet. For example, realizing that the blood-brain barrier has increased permeability in AD patients tells drug developers that treating AD involves strengthening the blood-brain barrier so it does not allow toxic substances (such as cytokines) to enter and trigger inflammatory responses. (Sharma et al., 2012) In addition, after researching more thoroughly into the claims of the initial reading on AD, I now understand that certain claims can often turn out to be monochromatic and therefore they must be taken with a grain of salt. The health and diet claims that are so prevalent on the web must be, in my opinion, scrutinized and considered comprehensively in order to be trusted, especially since our well-being is directly at risk.

All in all, my investigation on AD has taught me more than just causes or effects of the disease. My findings have led me to understand that critical evaluation and rational judgment (the weighing of pros and cons) is often necessary when we are faced with decisions to make the best choices, both for ourselves and for our society.

Resources:

Alzheimer’s facts and figures. (2013). Retrieved from http://www.alz.org/alzheimers_disease_facts_and_figures.asp

Alzheimer’s disease: Unraveling the mystery. (2008, September). Retrieved from http://www.nia.nih.gov/alzheimers/publication/part-2-what-happens-brain-ad/hallmarks-ad

Brown, C., & Ford, M. (n.d.). Medicine and drugs. In Higher Level Chemistry: Developed specifically for the IB Diploma Pearson Baccalaureate.

Cohen, R. M. (2009). The role of the immune system in alzheimer’s disease. The journal of lifelong learning in psychiatry, 7(1), 28-35. Retrieved from http://psychiatryonline.org/data/Journals/FOCUS/1837/foc00109000028.pdf

Fox, M. (2013, September 04). Better hygiene in wealth nations may increase alzheimer’s risk. Research at Cambridge. Retrieved from http://www.cam.ac.uk/research/news/better-hygiene-in-wealthy-nations-may-increase-alzheimers-risk

Fox, M., Knapp, L.A., Andrews, P.W., & Fincher, C.L. (2013). Hygiene and the world distribution of alzheimer’s disease. Evolution, medicine, & public health, 2013(1), doi: 10.1093/emph/eot015

Giubelei, F., Antonini, G., Montesperelli, C., Sepe-Monti, M., Cannoni, S., Pichi, A., & Tisei, P. et al., US National Library of Medicine, National Institutes of Health. (2003). T cell response to amyloid-beta and to mitochondrial antigens in alzheimer. Retrieved from PubMed.gov website: http://www.ncbi.nlm.nih.gov/pubmed/12714798

Khan, A. (n.d.). The amyloid hypothesis and potential treatments for alzheimer’s disease. The Journal of Quality Research in Dementia, (4), Retrieved from http://www.alzheimers.org.uk/site/scripts/documents_info.php?documentID=383&pageNumber=6

Mayo Clinic staff. (n.d.). Alzheimer’s: Causes. Retrieved from http://www.mayoclinic.com/health/alzheimers-disease/DS00161/DSECTION=causes

Pellicano, M., Larbi, A., Goldeck, D., Colonna-Romano, G., Buffa, S., Bulati, M., Rubino, G., Iemolo., F., Candore, G., Caruso, C., Derhovanessian, E., & Pawelec, G. (2012). Journal of neuroimmunology, 242(1), 52-59. Retrieved from http://www.jni-journal.com/article/S0165-5728(11)00305-5/abstract

Sharma, H. S., Castellani, R.J., Smith, M.A., Sharma, A., US National Library of Medicine, National Institutes of Health. (2012). The blood-brain barrier in alzheimer’s disease: Novel therapeutic targets and nanodrug delivery (10.1016/B978-0-12-386986-9.00003-X). Retrieved from PubMed.org website: http://www.ncbi.nlm.nih.gov/pubmed/22748826

Image Resources:

Beta-Amyloid (1-42) human [Web Graphic]. Retrieved from http://www.chemblink.com/products/107761-42-2.htm

Boosting Immunity: The Power of Vitamin C

With the frigid weather and seemingly incessant “colds” that everyone seems to be catching, the general assumption is that we all need an immune-system boost. As I was walking down the aisle of a bookstore a few weeks ago, I came across numerous magazines that claimed the phrase “boost your immunity and say good-bye to that nasty cold” – or words to that effect. As I casually picked up one of these million magazines and glossed over to the “boost your immune system” article, I was fully aware that I was going to read simply another one of those relatively ineffective and trite health articles that in my opinion always acted as “fillers” for the magazine. This time, however, while reading about the common antioxidant Vitamin C, I seemed to expect something deeper, something more than just the fact that it is a vitamin crucial to our immune system. Thus, at this point, I abruptly stopped reading and made a decision to research this topic myself, and quite surprisingly, have discovered that besides the superficial uses of Vitamin C as a health supplement, its antioxidant property allows it to be used even in the process of manufacturing plastic.

Vitamin C, also known as ascorbic acid (C6H8O6), acts as an antioxidant that is commonly known to be essential to our health – in particular, our immune system – and therefore protects us against damage done by called free radicals, which are reactive species (or molecules) that contain an unpaired electron. (Derry, Connor, & Jordan, 2008) It is a six-carbon lactone (an organic compound containing an ester group -OCO- as part of a ring) (New Oxford American Dictionary) that is synthesized from glucose in the liver of most mammalian species. (Padayatty et al., 2003) Because of its polar structure, ascorbic acid is a water-soluble molecule. Other properties include that the substance exists in its crystalline state as colorless (almost white) crystals and that it has a sour, acidic taste. (Shibata et al., 1996)

During the research process, I learned that antioxidants are substances that are preferentially oxidized, slowing down the oxidation of “oxidizable substrates.” (Derry, Connor, & Jordan, 2008) Evidence of oxidation includes either the loss of Hydrogen atoms, the gain of Oxygen atoms, or simply the loss of electrons. Therefore, based on my understanding of this definition, I discovered that the structures for the reduced (C6H8O6) and oxidized (C6H6O6) forms of the ascorbic acid antioxidant are shown below:

(Kstone, 2002)
(Kstone, 2002)

Ascorbic acid is readily oxidized to dehydroascorbic acid in the human body. (US National Library of Medicine, 2011) The ascorbic acid molecule contains 2 hydrogen atoms as well as 2 electrons that it donates/transfers to form the dehydroascorbic acid molecule. Thus, I can see that the ascorbic acid molecule undergoes an oxidation itself to form dehydroascorbic acid.

Once the ascorbic acid loses these 2 hydrogen atoms, it is left as negatively-charged ascorbate. (Milczarek, 2010) Ascorbate is then able to neutralize the very reactive free radicals in our body by donating its own electrons to them. This allows for the protection of cells in our body against excessive oxidation by dangerous free radicals, which can be obtained from external sources such as pollution, x-rays, smoke, and even internal (mental) sources such as stress. Excessive oxidation by free radicals causes aging and can potentially damage all cellular macromolecules including proteins, carbohydrates, lipids, and nucleic acids, which could very well lead to diseases such as cataracts, cancer, and other heart diseases. (Kumar, 2011) I was highly alarmed by how much damage free radicals could potentially cause in our bodies.

Nonetheless, with the presence of antioxidants such as ascorbic acid that are particularly noteworthy of combatting these free radicals that attack our cells, we can assure ourselves that because the various cells within our bodies are safe, the immune systems of ours is healthy too. (Harvard Health Publications)

(Nutragenetics, LLC, 2012)
(Nutragenetics, LLC, 2012)
(Hiren)
(Hiren)

So what are the implications of understanding the antioxidant Vitamin C? Apart from investigating the role that Vitamin C plays in protecting us against free radicals and boosting our immune system, I found that Vitamin C can be used in unexpected ways. Recently, Vitamin C has been found to be an environmentally friendly alternative in the process of manufacturing plastic, a material that we all know to be ubiquitous in our lives.

ATRP (atom transfer radical polymerization) is a plastic-manufacturing technique in which chemical subunits of the plastic polymers are essentially “coaxed” into chains. For the purposes of this blog post, I will focus on the implications of this process. Although ATRP is an effective method, it does come with costs because the process requires a copper catalyst that can leave unwanted waste in our precious environment. Based on my knowledge of copper as a transition metal as well as a catalyst, I know that in this polymerization reaction, the copper is neither a component of the reactants nor the products. The ATRP process requires an equal amount of two species of the copper catalyst (Cu+ and Cu2+) in order to produce a growing polymer chain. However, as the reaction progresses, there is significantly more Cu2+ than Cu+, and so typically, more Cu+ is added to the reaction to balance out the copper catalyst needed. Unfortunately, this results in overwhelmingly high levels of copper in the production of such polymers that would create economic costs too high for removal. (Ward, 2006) On the bright side, however, chemical engineers have found recently that adding “excess reducing agents” such as Vitamin C can reduce the amount of copper catalyst waste that is excreted into the air during the production of plastic material. Based on my knowledge of Vitamin C as an effective reducing agent, I know that it can donate its own electrons to the Cu+ and Cu2+ to compensate for their lost electrons, thus making the substance more safe and stable. The addition of Vitamin C into the ATRP process can dramatically reduce economic costs for producers and more importantly, decrease the waste in our environment. (Newswise, 2007)

In conclusion, I believe that performing such an investigation on the strength of Vitamin C as an antioxidant has allowed me to expand my knowledge – I never knew how deeply I could dig in terms of the chemistry of ascorbic acid! Overall, this research process has taught me how to truly connect my chemical knowledge to that of the real world.

References:

Deutsch, J. (2000). Dehydroascorbic acid. Manuscript submitted for publication, Department of Medicine, Divisions of Hematology and Gastroenterology, University of Colorado, , Available from Elsevier Science B.V. Retrieved from http://144.206.159.178/FT/553/12549/255666.pdf

Harvard Health Publications. (n.d.). How to boost your immune system. Manuscript submitted for publication, Health, Harvard, Boston, MA, Retrieved from http://www.health.harvard.edu/flu-resource-center/how-to-boost-your-immune-system.htm

Kumar, S. (2011). Free radicals and antioxidants: Human and food system. Manuscript submitted for publication, Institute of Food Technology, Bundelkhand University, Jhansi, India. , Available from Pelgia Research Library. Retrieved from http://pelagiaresearchlibrary.com/advances-in-applied-science/vol2-iss1/AASR-2011-2-1-129-135.pdf

Milczarek, A. (2010). Vitamin c. Informally published manuscript, Huntington’s Outreach Project for Education, Stanford, Palo Alto, CA, Retrieved from http://www.stanford.edu/group/hopes/cgi-bin/wordpress/2010/06/vitamin-c/

Newswise. (2007, 10 12). Vitamin c, water have benefits for plastic manufacturing. Reliable Plant Magazine. Retrieved from http://web.archive.org/web/20071012160442/http://reliableplant.com/article.asp?pagetitle=Vitamin C, water have benefits for plastic manufacturing&articleid=3133

Padayatty, S. J. et al. (2003). Vitamin c as an antioxidant: Evaluation of its role in disease prevention . Journal of the American College of Nutrition, 22(1), 18-35. Retrieved from http://www.jacn.org/content/22/1/18.full

Shibata, M. et al. International Program on Chemical Safety, (1996). Ascorbic acid. Retrieved from Inchem website: http://www.inchem.org/documents/pims/pharm/ascorbic.htm

Understanding free radicals and antioxidants. HealthCheck Systems, Retrieved from http://www.healthchecksystems.com/antioxid.htm

US National Library of Medicine, (2011). Ascorbic acid injection, solution . Retrieved from DailyMed website: http://dailymed.nlm.nih.gov/dailymed/lookup.cfm?setid=a6c36a36-28ee-4a1b-86fe-98ef94064b68

Vitamin C. (2013). In Encyclopedia Britannica. Retrieved from http://school.ebonline.com/all/eb/article-9075556?query=ascorbic%20acid&ct=null

Ward, L. (2006, October 10). Carnegie mellon scientists use “green” approach to transform plastics manufacturing process. Carnegie Mellon Press Release. Retrieved from http://www.cmu.edu/PR/releases06/061010_pnas.html

Images:

Hiren. (Designer). (n.d.). Fresh oranges. [Print Photo]. Retrieved from http://www.hiren.info/desktop-wallpapers/other-mix-pictures/fresh-oranges

Kstone. (07, 10 02). Determination of vitamin c. Retrieved from http://wwwchem.csustan.edu/chem1112/1112vitc.htm

Nutragenetics, LLC. (Producer). (2012). Pharmagenomix. [Print Photo]. Retrieved from http://www.nutragenetics.net/products.asp