Genetic Background of Alzheimer’s Disease

Alzheimer’s disease, the well known progressive neurologic disease of the brain, leading to irreversible loss of neurons and the loss of intellectual abilities, including memory and reasoning, which become severe enough to impede social or occupational functioning. There are multiple researchers and also it has carried an importance of current research which carried an important understanding about the genetical background of Alzherimer’s. [Know more about Alzheimer’s here: http://www.medicalnewstoday.com/articles/159442.php]

Here in this article I would like to highlight some major understanding about Alzheimer’s disease, especially the genetical research and understanding.

A research published in Journal of Neuroscience where the UK researchers, University of Kentucky identified several variations in DNA sequence, where each can modify Alzheimer’s risk. They identified a potential genetic variation near the gene CD33, which is thought to inhibit clearance of amyloid beta (a hallmark of Alzheimer’s disease, know more here http://med.stanford.edu/ism/2013/september/alzheimers.html). The results obtained, indicating the inhibition of CD33 may reduce Alzheimer’s disease. A drug was tested for acute myeloid leukemia targets CD33, suggesting the potential for treatments based on CD33 to mitigate the risk for Alzheimer’s disease. Although they suggested that further studies must be conducted before this treatment approach could be tested in humans.

Another research where four new genes have been identified where researchers from a consortium of 44 universities and research institutions in the United States, including Rush University Medical Center, identified four new genes linked to Alzheimer’s disease. The research was published in the journal Nature Genetics. The genetic analysis was performed with more than 11,000 people with Alzheimer’s disease, along with the same number of elderly people with no symptoms of dementia. Earlier a gene of apolipoprotein E-e4, APOE-e4, identified over 15 years ago, has the largest effect on risk. Then more additional genes was identified, CR1, CLU, and BIN1. But in through this research adds more four genes MS4A, CD2AP, CD33, and EPHA1 — and contributes to identifying and confirming two other genes, BIN1 and ABCA7, thereby doubling the number of genes known to play a role in Alzheimer’s disease.

The above two research investigates that CD33 plays major role in Alzheimer’s disease. Hence it allows easy focus that some cell signaling ability takes up a major role behind the unrevealed story behind this disease.

In the next recent research in 2013, researchers from Washington University School of Medicine in St. Louis identified several genes linked to the tau protein, which is found in the tangles that develop in the brain as Alzheimer’s progresses and patients develop dementia. APOE, had been identified as a risk factor for Alzheimer’s appears to be connected to elevated levels of tau. Researchers in an article said “Some of the effects are mediated through amyloid-beta and others by tau. That suggests there are at least two ways in which the gene can influence our risk for Alzheimer’s disease.” [Read More here: http://news.wustl.edu/news/Pages/25203.aspx]. Finally in addition to their research along with APOE, the researchers found that a gene called GLIS3, and the genes TREM2 and TREML2 also affect both tau levels and Alzheimer’s risk.

Regarding tau protein early research was carried out in 2009, published in The American Journal of Pathology based on the hypothesis that an unfolded protein response contributed to neurodegeneration in Alzheimer’s disease partially though its effects on the accumulation of hyperphosphorylated tau, a major component of tangles in Alzheimer’s disease patients. They identified that markers of the unfolded protein response were expressed in areas of tau accumulation in patients with Alzheimer’s disease.

So in conclusion of this report, it is obvious to understand that for any genetic analysis signaling pathway and protein modification towards a disease is important. Alzheimer’s disease which allows researchers to reach a proper research finding that Alzheimer’s disease are caused due to multiple gene involvement. Initially CD33 was identified which holds a major role on amyloid beta, followed by other genes too. “tau” protein also been identified to have some major impact on Alzheimers, hence amyloid beta along does not always play the role alone. Even in this story I pushed back a little from the solutions identified from the genetic analysis but the better understanding of correlation highlights major importance toward the disease.

References:

M. Malik, J. F. Simpson, I. Parikh, B. R. Wilfred, D. W. Fardo, P. T. Nelson, S. Estus. CD33 Alzheimer’s Risk-Altering Polymorphism, CD33 Expression, and Exon 2 Splicing. Journal of Neuroscience, 2013; 33 (33): 13320

Naj et al. Common variants at MS4A4/MS4A6E, CD2AP, CD33 and EPHA1 are associated with late-onset Alzheimer’s disease. Nature Genetics, 2011

Carlos Cruchaga, John S.K. Kauwe, Oscar Harari, Sheng Chih Jin, Yefei Cai, Celeste M. Karch, Bruno A. Benitez, Amanda T. Jeng, Tara Skorupa, David Carrell, Sarah Bertelsen, Matthew Bailey, David McKean, Joshua M. Shulman, Philip L. De Jager, Lori Chibnik, David A. Bennett, Steve E. Arnold, Denise Harold, Rebecca Sims, Amy Gerrish, Julie Williams, Vivianna M. Van Deerlin, Virginia M.-Y. Lee, Leslie M. Shaw, John Q. Trojanowski, Jonathan L. Haines, Richard Mayeux, Margaret A. Pericak-Vance, Lindsay A. Farrer, Gerard D. Schellenberg, Elaine R. Peskind, Douglas Galasko, Anne M. Fagan, David M. Holtzman, John C. Morris, Alison M. Goate. GWAS of Cerebrospinal Fluid Tau Levels Identifies Risk Variants for Alzheimer’s Disease. Neuron, 2013

Hoozemans JJM, van Haastert ES, Nijholt DAT, Rozemuller AJM, Eikelenboom P, Scheper W. The Unfolded Protein Response Is Activated in Pretangle Neurons in Alzheimer’s Disease Hippocampus. American Journal Of Pathology, 2009

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Updated Story:

This is a little update of what I have mentioned earlier in this article. A new research analyzed and published in the journal Nature Genetics revealing eleven new genetic susceptibility factors for Alzheimer’s Disease. An article published on 27th October 2013 at Science Daily news blog here: http://www.sciencedaily.com/releases/2013/10/131027185319.htm

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About Saumyadip

Science Communicator and Biologist. Keep interests in host-pathogen interaction research. Specifically bacterial infection mechanism, host infection evasion and immune susceptibility of host. Working as Senior Research Fellow at Thrombosis Research Institute, Bangalore.
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