Biology 202
2000 First Web Report
On Serendip

Imagine what it would feel like to start forgetting things, like directions to a familiar place or recent events. A sort of haze starts to surround what used to be the clear picture of reality and self. Then you start to lose the ability to make decisions, or make simple plans, and eventually lose the ability to do everyday activities by yourself, such as eating, or going to the toilet. Perhaps it is like falling down a deep, dark well, as time passes the real world becomes distant, and of course you have no control. Until finally you donât even recognize family members, and ultimately yourself. By this point you do not even realize if you are falling , the darkness prohibits you from recognizing what is happening.

Although the thought of it happening to yourself is scary, it is sad and even tragic if it happens to a loved one. Just imagine if one day your grandparents, or your parents not even remembering who you are. The person who loved you since the very day you were born does not even recognize you. Physically they are there, but in reality they are not. If brain is behavior, and the brain is not what it used to be, their behavior is no longer the same.

History and Biological Explanation.

While nearly a hundred years has passed since Alzheimerâs discovery, Alzheimerâs Disease has only become a important issue in recent years. Because increasing age is such a big factor in getting Alzheimerâs it was only a rare disease in the early-mid 20th century when people only lived until they were fifty. However with the increase in life expectancy in recent decades where many people live well into their seventies and eighties, Alzheimer has become a disease that effects quite a large proportion of the population. Most sources put the figure as 3% of the population between 65-74, 19% of the population between 75-84 and half of the population over 85 (1).. Although it has been observed that there has been several cases of people under 60 being diagnosed with Alzheimerâs but these are considered rare cases.

Perhaps one of the main reasons why a cure to Alzheimerâs is yet to be found has to do with doctors not even knowing the cause of it until quite recently. Research on senile plaques has been progressing steadily since the 1980âs when scientists connected amyloid precursor protein (APP) with the formation of the plaques(1). Our bodies produce three enzymes alpha, beta, and gamma secretase that cut the APP into shorter forms. The alpha secretase splits up the APP into a harmless protein, but the beta and gamma enzymes create a stickier protein called beta amyloid-42 (A-beta) (2). While we all produce A-beta, what happens to Alzheimerâs patients is that the A-beta builds up in the fluid surrounding the neurons to form plaques.

People with Alzheimerâs produce as much A-beta as would a normal person, but for some reason they have difficulty disposing it. What happens in a healthy person is that after A-beta drifts away from the cell it just dissolves. However as we age, these A-beta folds into an insoluble form called fibrils. The nervous system sees these fibrils as foreign substance and initiates an inflammatory response. What ultimately happens is that neurons die from the free radicals, the toxin used to fight infections (2).

Presently, it is seen that neurofibrillary tangles are connected to a protein called tau which exists in the cerebrospinal fluid(1). In a healthy person, the appendages of neurons are built around microtubles that gives the neuron its shape while also transporting chemical messangers and nutrients. Tau serves to bind and reinforce the microtubules with the neurons (2). What happens in people with Alzheimerâs is that these tau molecules detach themselves and form knot like shapes. As this happens, both the microtubles and neurons die off, thus people start to lose memory, and eventually control over their body.

The next step in trying to solve the mystery behind the cause of Alzheimerâs is why the normal tau molecules suddenly stop doing what they have been doing for 60-70 years. Just a few months ago a team of Harvard researchers connected the enzyme cdk5 as the source of tau tangling.

Some researchers say that amyoid (A-beta) plaques pressing against the neurons causes chemical reactions to take place, and that the detaching and tangling of tau molecules are one of the results of the chemical reaction (2).

There has been other researchers who have been looking towards other causes. A possible source is calcium. Researchers claim that Alzheimerâs disease causes a change in the calcium regulation system and thus result in an accumulation of calcium in the brain that eventually kills the brain. Another possibility is aluminum; this comes from the fact that some Alzheimerâs victims have high levels of aluminum in their brain tissues. Researchers now say that any connection with aluminum probably has more to do with Alzheimerâs making the brain tissues more susceptible to aluminum, rather than aluminum being the main reason (3).

Factors: How do we know who will get Alzheimerâs?

Perhaps the root of the mystery surrounding Alzheimerâs is that it is hard to point to one real factor of who gets Alzheimerâs. It is not like HIV/AIDS a disease caused by a virus nor is it like sickle cell anemia and many cancers a genetic one. Presently it is believed that there are more than one factor for people to get Alzheimerâs and different people get it for different reasons (4).

Perhaps the most obvious and likely factor is genes. A research conducted in 1996 of 13,000 people found that people who had/has two parents with Alzheimerâs have a 54% risk, which is 1.5 times the percentage for people with only one parent, and 5 times the risk for people whoâs parents did not have Alzheimerâs (1). Yet it is wrong to point to genetics as the cause because there are cases of identical twins with one having Alzheimerâs and the other being perfectly healthy (2).Surveys have found that people who have an identical twin with Alzheimerâs have a 40-50% risk which is much higher than the average person but not high considering the identical twins originally share the same genes (1).

In recent years a few genetic mutations have been found which are known to be connected to Alzheimerâs. Chromosome 21 which is more known for its connection to Down syndrome also happens to be the gene which controls APP. People with Down syndrome produce extra APP, and thus have more A-beta. Thus it has been seen that people with Downsyndrome almost always develop Alzheimerâs if they live onto their 40âs and 50âs (1).

Environment:

The example of the identical twins shows that although they probably play a major role, is not the only factor and that the environment plays a significant role. A study conducted on African Americans older than 65 showed that people of rural backgrounds with less than seven years of education were 6.5 times more likely to have Alzheimerâs than an educated person of urban background. Another research found that people with more than five siblings are more likely to have Alzheimerâs. These two findings show that people with ãmore nurturedä brains are more resistant to forming Alzheimerâs (2).

Another research supporting the environmental factor over the genetic one involves Japanese-American males and Japanese males. A test conducted over a thirty year period showed that while the percentage of Japanese-Americans with Alzheimerâs was 5.4% while the Japanese in Japan had a mere 1.5%. This shows that while Japanese-Americans are genetically no different from Japanese in Japan, the percentage of people with Alzheimerâs is much closer to European and American males.

Virus:

Some scientists believe that viruses trigger Alzheimerâs disease. These viruses possibly are the source of changes in the brain tissue which initiates the declining process inside the brain.

Some interesting facts:

At all ages, women are more likely to get Alzheimerâs. By the time they reach 93 they are 13% more likely then men to get Alzheimerâs (1).

Research has found that Cherokee Indians are resistant to Alzheimerâs. Research conducted amongst people of Cherokee Indian ancestry has found that the stronger oneâs ancestry is to Cherokee Indians the less likely the changes became of having Alzheimerâs.

It is hard to isolate one source, and what is most likely the case is that like cancer, environmental factors instigate the gene to start to behave differently, thus causing the disease.

Treatment, improvements, and a cure:

Recent research has shown that vitamin E, non-steroidal anti-inflammatories (NSAID), and estrogen delay the onset of Alzheimerâs (5).

Though there still is no cure, or even an effective treatment for Alzheimerâs researchers are very optimistic. Dr. Bruce Yankner of Harvard Medical School says "We've learned more about Alzheimer's in the past 15 years than in the previous 85," (1). Importantly, there has been several new discoveries involving the nature of the disease, cures, symptoms, and treatments just within this past year. Although many mysteries still surround Alzheimerâs many doctors and researchers are quite optimistic about the chances of finding a cure.

Conclusion:

If Emily Dickinson is right, and the brain is wider than the sky, for people with Alzheimerâs itâs like the sky is falling down, if the Brain is deeper than the sea, for people with Alzheimerâs it become a puddle, and if the Brain is just the weight of God, than people with Alzheimerâs is no more than a mere man.

WWW Sources

2)http://newsweek.com/nw-srv/printed/us/so/a54596-2000jan23.htm, An article from Newsweek that came out 2 weeks ago that wrote about recent developments

3)http://www.pslgroup.com/ALZHEIMER.HTM

4)http://www.alzheimers.org/index.html ,Alzheimer's Association

5)http://www.alz.org/, Alzheimer's Disease Education and Referral (ADEAR) Center's website

6)http://www.alz.co.uk/alz/index.html, Website of Alzheimer's Disease International

Additional Websites on Alzheimer's Disease

B)http://www.pslgroup.com/ALZHEIMER.HTM,

C)http://www.alzheimers.org.uk/ , Alzheimer's Disease Society

D)http://newsweek.com/nw-srv/printed/us/so/a54600-2000jan23.htm , From Newsweek showing drawings of what happens in the neurons

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