Saturday, 26 May 2012

Genetic factors in Alzheimer's


Degeneration in the language and memory centers
WebMD 2009

    Alzheimer’s disease is the most prevalent type of pre-senile dementia in the world. Patients suffering from Alzheimer’s can present symptoms of memory loss, deterioration in speech, comprehension, inability to concentrate, emotional outbursts and loss of coordination (WebMD 2009). Although the disease has been recognized for almost a century, the aetiology has not been clearly identified except for some significant revelation of facts recently. Thomas Bird from the University of Washington attempts to identify and justify the genetic causation in his article, Genetic factors in Alzheimer’s disease in the New England Journal of Medicine (year).

    In his paper Bird analyses new observations in the past 25 years that have greatly affected our understanding of Alzheimer’s. 

  • The accumulation and deposition of beta amyloid peptide plaques (Aβ peptide) in the brain is a major component in the clinical manifestation of the disease (GenScript 2012). 
  • This peptide is a fragment of the amyloid precursor protein, the gene for this protein (APP) is located on chromosome 21 (U.S National Library of Medicine 2008 & Bird 2005). 
  • According to recent observation the pathological changes in the brain caused by Alzheimer’s are also present in adults suffering from Down’s syndrome (trisome 21). 
  • When Alzheimer’s was first identified it was not related to inheritance, although now it is clear from the abundance of families that have multiple members suffering from the disease that it is has an autosomal dominant inheritance (Bird 2005). 
  • It has been found that ε4 allele of the apolipoprotein E (APOE) gene increases the risk of developing late onset (>65 years) Alzheimers which is the most common type (WebMD 2009 & Bird 2005).   
  • Mutations in specific genes related to the production of secretase proteins, which interacts with amyloid peptides, can also cause Alzheimers disease. 
   Point mutation, a single change in the base sequence of the gene, can result in an inheritable form of the disease that is identical to the non-genetic form but at a much younger age, typically in the 40s or 50s (Toland 2011). A change in the APP gene localised to the ß-, γ- and a-secretase sites where the Aβ peptide is fragmented from the amyloid precursor protein is also a mutation that can cause Alzheimer’s. In addition, a mutation in the gene coding for the proteins presenilin 1 and 2, which serves a role in the function of the γ-secretase can also be a cause. The ultimate result of these mutations is the accumulation of the pathogenic form of the amyloid protein in the brain, which leads to Alzheimer’s. However, gene mutations are only responsible for less than 2% of Alzheimer’s cases (Bird 2005).
(The University of Utah, 2012)

    Furthermore, the presence of the ε4 allele of the apolipoprotein E gene greatly increases the risk of developing Alzheimer’s, and the inheritance of homozygous ε4 allele further increases the risk. However, the allele is not essential for the disease to present and is not the only cause by itself. Further genetic linkage analysis studies are showing evidence supporting that there are additional genes influencing the risk, and the age at which the disease may appear (Bird 2005). 

    Bird highlights and explains the role genetics play in the identification of the causes of Alzheimer’s disease. This factor that was not considered as significant in the causation of Alzheimer’s 20 years ago is now recognized through the work of scientists such as Bird. Further observational and experimental investigations into the genetic component of Alzheimer’s disease and the interactions of amyloid proteins and genetic mutations are producing advanced data that is opening up possibilities for new treatment for this complex neurological disease.


Reference List


Bird, T.D 2005, ‘Genetic factors in Alzheimer’s disease’, The New England Journal of Medicine, vol. 352, no. 9, pp. 862-4.


GenScript 2012, Beta Amyloid Peptides, viewed 15th March 2012.


Toland, A.E 2011, DNA Mutations, Genetic Health, viewed 15th March 2012.


U.S National Library of Medicine 2008, Genetics Home reference, viewed 15th March 2012.
<http://ghr.nlm.nih.gov/gene>


WebMD 2009, Alzheimer’s Disease Health Center, viewed 15th March 2012.


 The University of Utah 2012, Alzheimer's Disease, viewed on 25th March 2012. 








1 comment:

  1. a drug was found to cure the alzheimer’s disease. Its drug called bexarotene. It was approved for a type of skin cancer since 1999. When experiment are conducted with mice the drug cleared away beta-amyloid in the brain that causes cognitive deficits in alzheimer’s disease. This is not the first time, there’s was alzheimer’s vaccine that cured the nerve destroying amyloid protein that deposits in animal brain. Later the scientists are disappointed when it failed to the same in humans. Another hope was found again enzyme, gamma secretase it efficiently decreased the formation of amyloid. It only worked in brain of mice but the disease got worse in human brain.

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