Kat Boardman

Biology 1

Lab Group A

It was the year 1901; Dr. Alois Alzheimer was the Director for Cerebral Anatomical Laboratory

when the case of a woman named Auguste D[eter] (Lage, 2006) came into his studies. Her family was

upset because this woman was acting strange, she had dementia. The world thought of this to be

insanity, they had yet to figure out that this was a disease. Dr. Alzheimer studied Auguste from ages 51

to 56 (Lage, 2006). After several rough years of living and fighting this unknown disorder, she died

from a pressure ulcer infection and pneumonia. Upon her death, Dr. Alois Alzheimer asked for a copy

of her autopsy report. “He was the first to describe the microscopic lesions” (Lage, 2006) those lesions

he found are what we now know today are neurofibrillary tangles (Pithadia, 2008).

To best understand Alzheimer's Dementia would be to understand the components of this

disorder. “Cognitive dysfunction we call dementia is simply the way the body expresses injury to a

myriad of insults that can be quite different from person to person” (Hyman, 2008). This disease is a

neurodegenerative disorder (Mayeux, 2003) in which your brain cells are slowly destroyed. As the

nerve cells die, the brain of someone with AD will eventually shrink and build up protein that is

increasingly harmful to the remaining healthy cells. These nerve cells lay within the area of one's mind

that retains the information of memory, logical thoughts, personality traits, movement, and a few more

(Northwestern University, 2008). That is why these are the first things to go, or key signals that

someone is developing or has Alzheimer's. There are many aspects of AD that are still unknown. It is a

complex disease that scientists and health care professionals are still studying and developing. With

new research gained they can agree that this can be traced back to a person’s genome, including

specific chromosomes.

Genes have an important part in understanding Alzheimer's disease. Genes are DNA, and that
controls who we are and what we become. Chromosomes are found in the nucleus of a cell, they

contain most of the organism's DNA. The particular place where a gene is located on the chromosome

is called the locus, or loci for plural. This encodes for a certain trait such as eye color or blood type.

Alleles are different variations for a single gene type. One gene can exist in multiple versions, say blue

or green eyes. As humans we have diploid cells that are a pair of homologous chromosomes one

inherited from each parent. These chromosomes are what swap randomly during replication.

Sometimes they happen with no problem, other times genetic mutations can occur, resulting in faulty

genes. Genes contain information; they patiently wait on the chromosome to be transcribed than

translated into an amino acid sequence. Through a series of events, DNA makes proteins that

“determine the capabilities of the cell and organism.” (Campbell, Dickey, Reece, Simon & Taylor,

2009.) These proteins that generate from the faulty genes are what eventually become toxic to a person

who has dementia.

Alzheimer's Dementia to an outsider may seem like the person is just acting crazy, insane, or

doing it for attention. This person can range from 50 to 80 years of age has no control of their actions.

The amount of time one spends living with dementia effects their reaction to the world around them.

They may know you one time you see them, and the next time they are frightened and think you will

hurt them. The people who have this, sometimes they know they are loosing their mind, and apologize

for their actions. It takes a great toll on them mentally for that reason, they develop severe depression.

They may know that they are becoming a burden and can see if someone is upset, or they will be

completely oblivious to that and everyone around them. Alzheimer's is the leading dementia;

Parkinson's Disease would be the second most common neurological disorder. Alzheimer's affects your

memory first, than your gait; it appears that a person forgets how to walk. Parkinson's affects your

mobility, than your mind. A patient with Parkinson's was up and about conversing with visitors, later

than night he lay in bed unable to move his legs. He had a hard time communicating with the staff, he

knew it was happening but could not stop it. As their nerve cells degrade their ability to function as
they used to worsens. Their actions become unknown, they try to get out of bed and fall to the floor

because they forgot how to walk. The care for these patients is a full time job; there is a life on the line.

There are few types of dementias; there are two forms of Alzheimer's disease; Familial

Alzheimer's Disease (FAD) and Sporadic (SAD). Familial is early-onset (before age 50-60), that

follows the autosomal dominant inheritance pattern (Holston & Schutte, 2006). While Sporadic is late-

onset, this usually effects people around age 70-80. “Gene mutations that cause the common, late-onset

form of Alzheimer's” (Kalb, 2006) are still developing.

Each protein that causes Alzheimer's comes from a gene that is on a chromosome; therefore

each particular strand of Alzheimer's has its own chromosomes that identify it. “Amyloid precursor

protein gene, located on chromosome 21... Presenilin-1, located on chromosome 14, and presenilin-2,

located on chromosome 1” (Feightner, Garcia, Hsiung, MacKnight, Patterson, & Sadovnick, 2008).

These are related to FAD. Studies show that the Apolipoprotein E (apoE) gene located on chromosome

19 is related to late-onset FAD but also related to early/late-onset SAD (Ilyas, 1995). Alpha-2-

macroglobulin locus on chromosome 12 is associated with SAD (DeVrieze, Holmans, Shears, & Wu

1998). Members from the glutathione S-transferase family, GSTO1 and GSTO2 located on

chromosome 10 would be newer evidence. This happens to be in Alzheimer's and Parkinson's patients,

suggesting a link between the two diseases (Helmuth, 2003). Through a way of testing the single

nucleotide polymorphism- SNP (Campell et al. 2009) of a gene called NEDD9, they were able to use a

RFLP- Restriction Fragment Length Polymorphism (Campell et al. 2009) to test if NEDD9 had a

relationship between AD and PD patients. They knew that an allele of this was a frequent genetic

factor. Finding that the “SNP of the NEDD9 gene is at best a weak genetic determinant of AD or PD”

(Amouyel, Campion, Chapuis, Elbaz, Hannequin, Lambert, Lendon, Mellick, Moisan, Pasquier, &

Silburn, 2008).

The proteins that are made from these chromosomes may cause nerve damage in a person’s

brain that has Alzheimer's Dementia. This nerve damages comes in two main forms neurofibrillary
tangles (Pithadia, 2008) and plaques. The brain of a patient without AD the tau protein is essential for

nerve fiber growth and development (Pithadia, 2008). “Tau protein is known for its role in the

stabilization of microtubules, which is important for the generation and maintenance of neurites”

(Eckert & Rhein, 2007). Microtubules serve as tracks for the movement of mitochondria and various

other organelles (Campell et al. 2009). In the patient of an AD brain the tangles are twisted nerve fibers

composed of abnormally hyperphosphorylated microtubular protein tau (Eckert & Rhein, 2007). The

plaques are from the intracellular and extra cellular amyloid-beta protein fragments that build up

between nerve cells (Gallo, 2007). The tangles and plaques damage the healthy cells surrounding them.

As the nerve cells die the ability to transmit information digresses. The build up of plaques takes time

to reach the full effect. This is why this dementia occurs later in life.

Another possible study for this disease is subjected to prions, these are “an infectious form of

protein that may multiple by converting related proteins into more prions” (Campell et al. 2009). A

prion takes a normal protein and changes it shape, therefore changing its function (Carrell & Lomas,

1997). These are looking at what happens when the beta-pleated sheets of the plaque proteins become

toxic by the prions ability to change its structure. The generally soluble to insoluble format is a case for

concern as the conversion has the ability to kill neurons (Goldberg, 2007). All of these factors are

important to discovering if one has or had Alzheimer's. Some may be tested and some are just known

instances that occur.

Genetic testing is difficult, in order to really understand what is going to happen one really

needs to know their family history. To fully grasp what is going to happen, especially with age-of-onset

one would need to know their mother/father's medical history, and even the health status of their

brothers and sisters. This is getting increasingly difficult as time goes by, with families splitting up and

medical history only shared with whomsoever has their name listed as the durable or medical power of

attorney.

Medical tests are improving and can be done to determine whether or not you have theses
alleles or mutations. Although they are improving it is regarded as dangerous to ones mental health to

have these done for your own curiosity. In October of 1995 (“A New Tool”, 1995) a group of people

got together to decide the appropriateness of testing for this. They concluded that apoE testing should

be done only for people who already show signs of having Alzheimer's Dementia as a way of treating

the disease, along with other methods. Not only does it concern your future, but the tests are not a

100% guarantee, it simply states you have this in you, and it may or may not fully develop to dementia.

Apolipoprotein E located on chromosome 19 has great important for genetic testing of AD. It

has many alleles, three of which are very important to this dementia. “Everyone has the APOE gene,

but what differs across people is which variant they happen to have: epsilon 2, epsilon 3 or epsilon 4”

(Florida State, 2008). This is a gene that is passed from your mother and your father, the apoE4 allele is

at best a risk factor for developing AD. Some people who obtain this allele will get Alzheimer's, while

some people who have AD do not have this allele (Journal of Clinical Investigation, 2008). The ethical

and privacy concerns of genetic testing are on the rise (Kalb, Mummolo, & Underwood, 2006).

Environmental and non-genetic factors influence Alzheimer's Dementia as well as hereditary.

One non-genetic factor is high cholesterol, as one of the proteins listed above carries cholesterol. A

study from the University of North Dakota School of Medicine and Health Sciences revealed that a cup

of coffee a day may reduce your chance of Alzheimer's as the caffeine helps block “disruptive effects of

high cholesterol that scientists have linked to Alzheimer's disease” (University Of North Dakota, 2008).

High blood pressure is another non-genetic factor. Environmental factors such as smoking, low

education, head trauma and “head injury accompanied by loss of consciousness” will increase your

chances. “Occupational exposure to environmental toxins such as pesticides, fertilizers, fumigants and

defoliants was associated with an increased risk of Alzheimer disease” (Feightner et al. 2008).

Today studies are being done to further explore the effect of Alzheimer’s on the brain, life,

family members, race, heredity, and just about everything else. New chromosomes are found and being

suggested as links between Alzheimer’s and Parkinson’s. There is an official Alzheimer organization
dedicated to raising awareness about this debilitating disease. AD is a national and worldwide concern,

it affects people everywhere. The numbers are on the rise, currently 4 million people have this and

suggest that by the year 2050 it will grow to13.2 million (National Institute on Aging, 2008). Scientists

are learning more everyday; there is no single cause for it but they do know there is no cure. Drugs can

delay or help with the symptoms of, but not prevent Alzheimer’s dementia. All one can do is wait,

hope, learn and be patient for Alzheimer’s is not going away any time soon.

Alzheimer's came about many years ago in the sense of brain damage. It is a neurological

disorder that denatures ones nerve fibers. The part of your brain that is effected first is your memory.

The nerve fibers become damaged because the proteins they come from are genetically mutated. Some

of the chromosomes that the genes come from are inherited (FAD) while others are not (SAD). The

inherited ones count for less than 10 percent of the population with this dementia. Alzheimer's and

Parkinson's are weakly genetically related. There is only one statistically relevant chromosome in the

two dementias. Genetic testing is available for those who already have AD; or done during autopsy for

verification or scientific purposes. There are more than genes that cause Alzheimer's, environmental

and life factors take a roll in developing dementia too. If you want to find out if you are going to get

this, the evidence now is not to be used for such reasons like curiosity. What you should do is enjoy

your life to the fullest so at someday, if you become one of the increasingly elders with this, you can at

heart know you lived a good life.

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