Alzheimer's+Disease


 * Alzheimer's Disease **

Alzheimer's is a degenerative disease taking place within the brain that causes dementia by attacking nerve cells in the cortex area of the brain as well as areas surrounding it (Figure 1). As stated by Pennsylvania Senator Arlen Specter: “Alzheimer’s has struck some four million Americans, at an enormous cost in human suffering, family suffering, and dollars and cents.”(Alzheimer’s disease, 1998). Being such a devastating disease, it can lead to impairment of the individual's emotions, recognition, coordination, memory, and the loss of mental functioning. It is classified as a form of dementia in which an individual starts progressively losing everyday abilities until they become completely dependent on someone else to care for them. There are two types of Alzheimer's: early onset and late onset. Researchers of the disease also commonly refer to these two categories as familial Alzheimer's disease (early onset) or sporadic Alzheimer's disease (late onset). A variety of things such as amyloid plaque, neurofibrillary tangles, nerve cell death and so much more are believed to be related to the development of Alzheimer’s. (Alzheimer’s Association, 2012; Alzheimer’s Disease Fact Sheet, 2011; Palmer //et. al//, 2011).

A healthy individual contains forty-six chromosomes, divided in twenty-three pairs. Half these pairs obtained from the father and half obtained from the mother. Within these chromosomes there are two types of genes that can determine whether an individual develops a disease or not: risk genes and deterministic genes. Risk genes increase the possibility of developing a disease, but their presence does not guarantee having the disease. On the other hand, deterministic genes directly cause a disease and anyone that inherits these genes will develop the disorder. The chromosomes numbered as 1, 14, 19, and 21 show evidence that link them to Alzheimer’s disease. (Figure 2). (Brooker, 2009, p. 45-68; Is Alzheimer’s Disease Genetic?, 2009). Genetic research is currently focusing on heredity to find out the risks for family members to develop numerous diseases. Changes to structure or number of these chromosomes in the DNA can cause chromosomal conditions that can lead to diseases such as Alzheimer's. Chromosome 1 is an autosomal chromosome, and the largest human chromosome that accounts for 8% of total human DNA. Changes in this chromosome can result in birth defects, delayed growth, development difficulties, and change in facial features. Chromosome 14 accounts for 3-3.5% of total human DNA. Changes to the chromosome 14 structure include delayed growth and development and distinctive facial features. Chromosome 19 accounts for more than 2% of the total human DNA. Chromosome 21 is the smallest chromosome in human DNA with about 47 million base pairs representing 1.5% of the total human DNA. Changes to chromosome 21 can cause intellectual disability, delayed development, and change in facial features. (Chromosomes, 2011). Early-onset Alzheimer’s is an uncommon form of dementia that affects people in their younger years. In recent studies two genes have been identified to cause early onset of the disease due to the defects in their structure. The gene amyloid precursor protein, //APP//, (Figure 3) is located on chromosome 21. When mutated, this gene causes abnormal forms of the amyloid protein. Mutations in the APP gene are insignificantly responsible for early onset cases of the disease. The most common case is a mutation that changes the amino acid valine to isoleucine. These mutations can lead to increased amounts of amyloid beta that can create amyloid plaques that accumulate in the brain leading to neurofibrillary tangles.(APP, 2011; Keller, 2010).
 * Early-Onset Alzheimer's (Familial Alzheimer's Disease)**

Gene presenilin 1, //PSEN1//, (Figure 4) is located on chromosome 14 and is responsible for the production of presenilin. Presinilin is a protein involved in maintaining neural survival and the transmission of chemical signals that activate genes for cellular growth and maturation. It has been roughly estimated that most cases of PSEN 1 mutations cause Alzheimer’s, because of the overproduction of amyloid beta peptide. In conclusion, APP and PSEN 1 mutations are believed to play the most crucial roles in developing early- onset Alzheimer’s. However, research has also linked PSEN 2 mutations the increases in amyloid beta peptide. Only one of these mutations needs to be present in a person’s DNA to possibly cause Alzheimer’s. (See Figure 3 -Genes //APP//, and //PSEN1//). (PSEN1, 2011; Sanchez, 2007).


 * Late-Onset Alzheimer's Disease (Sporadic Alzheimer's Disease)**

Most cases that fall under this category commonly affect individuals after the age of 60. T has only been one major gene believed to cause late-onset Alzheimers: The Alipoprotein E Gene, //APOE//, is very susceptible to mutations that can cause Alzheimer’s. //APOE// has three major alleles that are all liable in acquiring mutations: //APOE// 2, 3 and 4. Any one mutation on one of these three alleles can cause the disease, which is known to be much more progressive than early-onset Alzheimer’s. (Norihiro et. al, 2009).

====**Diagnosis and Treatment** Thanks to the development in research regarding Alzheimer's we have learned that the disease is in fact inherited. However, it is still important to realize that there are other factors that can play a role in the development of the disease or lead to the development of other diseases. If an individual knows that they are hereditarily more susceptible to the disease then it is important to seek a doctor for proper diagnosis, and discuss possible treatments since some Alzheimer's symptoms can be reversible if found early on. Along with that, the progression of the disease may be less severe if diagnosis is prompt. Also, finding the disease early will allow the family members to make responsible plans as well as providing the necessary support for the affected individual. ====

====Research done by Reisberg B., (2012) has found that there have been seven key stages that seem to be apparent in the progression of Alzheimer’s. (Figure 6) While not everyone experiences the same systems from the time they are diagnosed and throughout the progression of the disease, these seven stages all involve generalized symptoms that most have experienced: Stage 1 obviously just involved the time when an individual has no apparent symptoms at all, but little do they know, the defects within their genes are already present. Stage 2 (Extremely Mild Cognitive Decline) involves an individual first realizing they are forgetting common everyday things, such as words, or tasks that needed completed. While they might notice these changes, most often times when evaluated doctors still cannot recognize any impairment in cognition and symptoms are most often believed to be age related. Stage 3( Mild cognitive decline) is when others begin to notice the individual having challenges such as remembering names, commonly used words, or where they have placed things. At this stage generally doctor’s can detect some signs. (Reisberg, B., 2012).====

====Stage 4 (Moderate Cognitive Decline) is when medical doctors can noticeably detect symptoms. When checked by a medical doctor one may notice the individual being challenged by forgetting things such as personal history or recent events. Also the person has trouble completing problems that involved a lot of mental focus. Also with these challenges an individual may seem easily frustrated. Stage 5 ( Moderately Severe Cognitive Decline) involved individuals needing help with every day activities. Along with this they may be unable to recall things such as their address or phone number and may need help dressing. Some common activities, such as using the restroom are still attainable on their own. (Reisberg, B., 2012).====

====Stage 6 ( Severe Cognitive Decline) is when an individual begins to need extreme help. Most often times during this stage the sufferer will show noticeable signs of personality changes. Along with that they will start forgetting names of important people in their lives and have no understanding of their surroundings. Also during this stage some lose the ability to control their bladder or bowels. Many may wander and their sleep patterns may change dramatically. Stage 7 ( Extremely Severe Cognitive Decline) is known as the final stage of the disease. During this stage individuals have no understanding of their surroundings, their communication skills are absent, and control of body movements declines. (Reisberg, B., 2012).====

==== When looking at these stages it is important to note that some stages might not be completely apparent of match up exactly with what was proposed, due to the fact that every individual experiences are a little bit different. Also sometimes symptoms of these stages are impacted by things such medications the individual is taking. With all this in mind it is also crucial to remember that while Alzheimer’s is a progressively degenerative disease, it is not the disease itself that kills the individual. For example, things such as severe loss of body movement, mentioned in stage 7 could result in things such as the individual losing the ability to swallow, which could later lead to death. ====

====**Medications:** The Alzheimer's association has made clear that at this time there is no cure for Alzheimer’s, but the use of drugs can lessen the severity of symptoms. The U.S Food and Drug Administration (FDA) has approved only two types of medication for memory loss: cholinesterase inhibitors and memantine. Alzheimer's affects the brain by decreasing the levels of acetylcholine which normally plays a role in mental functioning. Cholinesterase inhibitors improve the effectiveness of acetylcholine by increasing the levels in the brain or strengthening the nerve cell's response to it. Memantine lessens abnormal brain functioning, which makes daily actions easier but it does not halt the progression of the disease (Figure 7). (Alzheimer’s Association, 2012). ====

====Since each individual affected can have different symptoms and progression of the disease, individuals are encouraged to participate in research programs and clinical studies because it can help to find the cure for the disease. Also, the clinical studies can provide a better care for the individual and a peace of mind to the family since they are doing the best they can for their loved one. The clinical trials occur in phases which allow the medicine to accumulate in the system of the affected individual and increase the effectiveness of the drug.====

====**Medication Information** Donepezil, Galantamine, Tacrine, and Rivastigmine: are oral medications that are acetylcholinesterase inhibitors used to treat symptoms of Alzheimer's (dementia for example). Acetylcholine guides messages between nerve endings. Acetylcholineserase reduces acetylcholine. Alzheimer's decreases the amount of acetylcholine being produced in the brain causing acetylcholineserase to inhibit the small amount of acetylcholine left in the brain. Inhibiting acetylcholineserase allows the low amounts of acetylcholine to function causing neuron messages to flow. Galantamine, Tacrine, and Rivastigmine are used to treat Mild to Moderate stages of Alzheimer’s, while Donepezil is used to treat all stages of Alzheimer’s. Side Effects of each medication are similar (refer to Figure 7) (National Center of Biotechnology, 2010; Saltiel, E., 2005)====

====Memantine is an N-methyl-D-aspartate (NMDA) receptor inhibitor. This type of receptor is located on the surface of nerve cells and accepts many chemicals including glutamate. The neurotransmitter glutamate is produced and released by nerve cells. Glutamate is the main excitatory neurotransmitter and is thought to be responsible for nerve degradation. Inhibiting NMDA receptors decreases the effects of glutamate on nerve degradation. Memantine is used to treat Moderate to Severe stages of Alzheimer's. Side Effects are headache, constipation, confusion and dizziness (Figure 7) (Omudhome, O, 2005).====

====// Alzheimer's disease [electronic resource] : hearing before a subcommittee of the Committee on Appropriations, United States Senate, One Hundred Fifth Congress, second session : special hearing //. (1998). Washington, D.C. : U.S. G.P.O., 1998-. ====

==== Alzheimer's Disease Education & Referral. (2011, June). Fact Sheet. In //Alzheimer's Disease Genetics//. Retrieved March 25, 2012, from [] ====

==== Keller, L., Welander, H., Huei-Hsin, C., Tjernberg, L. O., Nennesmo, I., Wallin, Å. K., & Graff, C. (2010). The PSEN1 I143T mutation in a Swedish family with Alzheimer's disease: clinical report and quantification of Aβ in different brain regions. //European Journal Of Human Genetics//, //18//(11), 1202-1208. doi:10.1038/ejhg.2010.107 ====

==== Leonard, C., & Loup-Huret, J. (Artist).(2012). //Chromosome 1: G-banding, diagram and R-banding//. [Image of painting]. Poitiers, France; University Hospital. Retrieved March, 2012, from [] ====

==== Leonard, C., & Loup-Huret, J. (Artist).(2012). //Chromosome 14: G-banding, diagram and R-banding//. [Image of painting]. Poitiers, France; University Hospital. Retrieved March, 2012, from [] ====

==== Leonard, C., & Loup-Huret, J. (Artist).(2012). //Chromosome 19: G-banding, diagram and R-banding//. [Image of painting]. Poitiers, France; University Hospital. Retrieved March, 2012, from [] ====

==== Leonard, C., & Loup-Huret, J. (Artist).(2012). //Chromosome 21: G-banding, diagram and R-banding//. [Image of painting]. Poitiers, France; University Hospital. Retrieved March, 2012, from [] ====

==== Morreale, B. (Artist). //How the Brain and Nerve Cells Change During Alzheimer's Disease//. [Image of painting]. Clarksburg, MD; American Health Assistance Foundation. Retrieved March, 2012, from [] ====

==== Norihiro Takei, Akinori Miyashita, Tamao Tsukie, Hiroyuki Arai, Takashi Asada, Masaki Imagawa, & ... Ryozo Kuwano (a,. (2009). Genetic association study on in and around the APOE in late-onset Alzheimer disease in Japanese. //Genomics//, //93//441-448. doi:10.1016/j.ygeno.2009.01.003 ====

==== Palmer, K., Lupo, F., Perri, R., Salamone, G., Fadda, L., Caltagirone, C., & ... Cravello, L. (2011). Predicting Disease Progression in Alzheimer's Disease: The Role of Neuropsychiatric Syndromes on Functional and Cognitive Decline. Journal Of Alzheimer's Disease, 24(1), 35-45. doi:10.3233/JAD-2010-101836 ====

Reisberg, B. (2012). Seven Stages of Alzheimer's. In //Alzheimer's Assosiation//. Retrieved March 27, 2012, from []

Saltiel, E. (2005, April 11). Galantamine, Razadyne, Razadyne ER. In //MedicineNet.com//. Retrieved April 4, 2012, from []

Sánchez-Valle, R. R., Llad, A. A., Ezquerra, M. M., Rey, M. J., Rami, L. L., & Molinuevo, J. L. (2007). A novel mutation in the PSEN1 gene (L286P) associated with familial early-onset dementia of Alzheimer type and lobar haematomas. //European Journal Of Neurology//, //14//(12), 1409-1412. doi:10.1111/j.1468-1331.2007.01988.x

Stacy, K. M. (2008, April 15). Vitamin E May Up Alzheimer Survival. In //WebMD//. Retrieved April 4, 2012, from []

Is an uncommon form of dementia that affects people under 65 years of age. On recent researches three genes have been identified to cause the disease due to the defects in their structure. The gene amyloid precursor protein (APP) causes mutations due to formation of abnormal forms of the amyloid protein. The APP gene is located on the chromosome 21 at position 21.2 and it provides the instructions for the production of the protein amyloid precursor protein which is found in the brain and spinal cord. Mutations in the APP gene are responsible for 10-15% of all early onset cases of the disease. The most common case is a mutation that changes one of the building blocks- valine amino acid with isoleucine- at the position 717 of the gene. This mutations can lead to increased amounts of amyloid beta that can create amyloid plaques that accumulate in the brain leading to death of neurons (National Library of Medicine, 2012). Gene presenilin 1 (PSEN1) is located on chromosome 14 at base pairs 73,603,142 to 73,690,398 and it is responsible for the production of presenilin, a protein involved in the development of the brain and spinal cord and survival of neurons as well as the transmission of chemical signals from cell membrane to nucleus which activates genes for cell growth and maturation. Mutations in the PSEN1 gene is the most common cause of early onset Alzheimer's- a 70% of all cases. Another important function is that this gene is involved in the processing of the amyloid precursor protein and formation of soluble amyloid precursor protein (sAPP) which is involved in the formation of neurons. If only one of these mutations is to be present in the individual's DNA, it will develop to early onset Alzheimer's.

Is an uncommon  ** Alzheimer's Disease **  Alzheimer's is a degenerative disease taking place within the brain that causes dementia by attacking nerve cells in the cortex area of the brain as well as areas surrounding it (Figure 1) This can lead to impairment of the individual's emotions, recognition, coordination, memory, and the loss of mental functioning. It is classified as a form of dementia (loss of cognitive functioning) in which an individual starts progressively  Early-onset Alzheimer’s is an uncommon form of dementia that affects people in their younger years. In recent studies two genes have been identified to cause early onset of the disease due to the defects in their structure. The gene amyloid precursor protein, //APP//, (Figure 3) is located on chromosome 21. When mutated, this gene causes abnormal forms of the amyloid protein. Mutations in the APP gene are insignificantly responsible for early onset cases of the disease. The most common case is a mutation that changes the amino acid valine to isoleucine. These mutations can lead to increased amounts of amyloid beta that can create amyloid plaques that accumulate in the brain leading to neurofibrillary tangles.(APP, 2011; Keller, 2010). Gene presenilin 1, //PSEN1//, (Figure 4) is located on chromosome 14 and is responsible for the production of presenilin. Presinilin is a protein involved in maintaining neural survival and the transmission of chemical signals that activate genes for cellular growth and maturation. It has been roughly estimated that most cases of PSEN 1 mutations cause Alzheimer’s, because of the overproduction of amyloid beta peptide. In conclusion, APP and PSEN 1 mutations are believed to play the most crucial roles in developing early- onset Alzheimer’s. However, research has also linked PSEN 2 mutations the increases in amyloid beta peptide. Only one of these mutations needs to be present in a person’s DNA to possibly cause Alzheimer’s. (See Figure 3 -Genes //APP//, and //PSEN1//). (PSEN1, 2011; Sanchez, 2007).  losing everyday abilities until they become completely dependent on someone else to care for them. . There are two types of Alzheimer's: early onset and late onset. Researchers of the disease also commonly refer to these two categories as familial Alzheimer's disease (early onset) or sporadic Alzheimer's disease (late onset). It is believed that the development of amyloid plaque, neurofibrillary tangles, no connection between nerve cells, death of nerve cells, and beta amyloid are what cause the development of Alzheimer’s. (Alzheimer’s Association, 2012; Alzheimer’s Disease Fact Sheet, 2011).  form of dementia that affects people under 65 years of age. On recent researches three genes have been identified to cause the disease due to the defects in their structure. The gene amyloid precursor protein (APP) causes mutations due to formation of abnormal forms of the amyloid protein. The APP gene is located on the chromosome 21 at position 21.2 and it provides the instructions for the production of the protein amyloid precursor protein which is found in the brain and spinal cord. Mutations in the APP gene are responsible for 10-15% of all early onset cases of the disease. The most common case is a mutation that changes one of the building blocks- valine amino acid with isoleucine- at the position 717 of the gene. These mutations can lead to increased amounts of amyloid beta that can create amyloid plaques that accumulate in the brain leading to death of neurons (National Library of Medicine, 2012). Gene presenilin 1 (PSEN1) is located on chromosome 14 at base pairs 73,603,142 to 73,690,398 and it is responsible for the production of presenilin, a protein involved in the development of the brain and spinal cord and survival of neurons as well as the transmission of chemical signals from cell membrane to nucleus which activates genes for cell growth and maturation. Mutations in the PSEN1 gene are the most common cause of early onset Alzheimer's- a 70% of all cases. Another important function is that this gene is involved in the processing of the amyloid precursor protein and formation of soluble amyloid precursor protein (sAPP) which is involved in the formation of neurons. Most PSEN1 mutations will result in the production of abnormal presenilin 1 which will disrupt the processing of amyloid precursor protein and overproduction of amyloid beta peptide that can build up in the brain which is a characteristic of progressive signs of the disease. If only one of these mutations is to be present in the individual's DNA, it will develop to early onset Alzh Alzheimer's is a degenerative disease of the brain that causes dementia by attacking nerve cells in the cortex area of the brain as well as those areas surrounding it. This leads to an impairment of the individual's emotions, recognition, coordination, memory, and the loss of mental functioning. It is classified as a form of dementia (loss of cognitive functioning) in which an individual starts by losing some abilities until it depends completely in another individual to perform daily tasks. There are two types of Alzheimer's- early onset and late onset and the individuals that are usually affected after the age of 60, but those who research the disease refers to two other categories familial Alzheimer's disease (early onset) or sporadic Alzheimer's disease(late onset). Alzheimer's disease is characterized by the development of amyloid plaque, neurofibrillary tangles, no connection between nerve cells, or death of nerve cells, and beta amyloid. A healthy individual contains 46 chromosomes, divided in 23 pairs. 23 obtained from the father and 23 obtained from the mother. There are two types of genes that can determine whether an individual develops a disease or not: risk genes and deterministic genes. Risk genes increase the possibilities of developing a disease but their presence does not guarantee it while deterministic genes directly causes a disease and anyone that inherits the disease will develop the disorder. The chromosomes numbered as 1, 14, 19, and 21 showed evidence that link them to the disease (Figure 1). Genetic research is currently focusing on heredity to find out the risks for families to develop the disease. Changes to structure or number of these chromosomes in the DNA can cause chromosomal conditions that can cause diseases such as Alzheimer's. Chromosome 1 is a non-sex chromosome, and the largest human chromosome that counts for 8% of the total human DNA. Changes in these chromosomes can result in birth defects, delayed growth, development difficulties, and change in facial features. Chromosome 14 has 106 million DNA building blocks that counts for 3-3.5% of total human DNA Changes to the chromosome 14 structure include delayed growth and development, and distinctive face features. Chromosome 19 contains around 64 million base pairs that represent more than 2% of the total human DNA. Chromosome 21 is the smallest chromosome in human DNA with about 47 million base pairs representing 1.5% of the total human DNA. Chromosome 21 can cause intellectual disability, delayed development, and change in facial features. Identified changes from this chromosomes include partial monosomy 21(missing segments) and ring chromosome 21(chromosome breaks in two places and ends of chromosome fuse to form a ring structure). (National Library of Medicine, 2012)