Eva & Alex's Research Paper

Independent Research Paper Sources

Alzheimer's Disease Genetics Fact Sheet
http://www.nia.nih.gov/NR/rdonlyres/3C4B634E-A2D8-4415-927F-4B79BEC47EA6/11207/84206ADEARFactsheetGeneticsFINAL08DEC23.pdf

Identification of Novel Genes That Modify Phenotypes Induced by Alzheimer's β-Amyloid Overexpression in Drosophila
http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=2278065

A Cladistic Analysis of Phenotypic Associations with Haplotypes Inferred from Restriction Endonuclease Mapping or DNA Sequencing. V. Analysis of Case/Control Sampling Designs: Alzheimer's Disease and the Apoprotein E Locus
http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=1205505

Overexpression of ABCA1 reduces amyloid deposition in the PDAPP mouse model of Alzheimer disease
http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=2200302

The National Cell Repository for Alzheimer's Disease
http://ncrad.iu.edu/BackgroundInfo/index.asp
http://ncrad.iu.edu/forFamilies/genetics.asp
http://ncrad.iu.edu/forFamilies/autopsy.asp

Genetics, transcriptomics and proteomics of Alzheimer’s disease
http://www.pubmedcentral.nih.gov/picrender.fcgi?artid=2259384&blobtype=pdf

Risk and protective effects of the APOE gene towards Alzheimer’s disease in the Kungsholmen project: variation by age and sex
http://www.pubmedcentral.nih.gov/picrender.fcgi?artid=1739059&blobtype=pdf

Rapid cognitive improvement in Alzheimer's disease following perispinal etanercept administration
http://www.jneuroinflammation.com/content/5/1/2

*just a comparison of the brain of a healthy person versus someone with AD*
http://en.wikipedia.org/wiki/File:COMPARISONSLICE_HIGH.JPG

Genetic (Inherited) Factors—-Fisher center for Alzheimer's Research Foundation
http://www.alzinfo.org/alzheimers-genetic.asp

apoE isoform–specific disruption of amyloid β peptide clearance from mouse brain
http://www.jci.org/articles/view/36663/pdf

Genetics, transcriptomics and proteomics of Alzheimer’s disease
http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=2259384&tool=pmcentrez

ApoE promotes the proteolytic degradation of Aβ
http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=2493297&tool=pmcentrez

Reversal Of Alzheimer's Symptoms Within Minutes In Human Study
http://www.sciencedaily.com/releases/2008/01/080109091102.htm

The Association Between Genetic Variants in SORL1 and Alzheimer Disease in an Urban, Multiethnic, Community-Based Cohort
http://archneur.ama-assn.org/cgi/reprint/64/4/501.pdf

Protein Aggregation in the Brain: The Molecular Basis for Alzheimer’s and Parkinson’s Diseases
http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=2274891

~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~ Printed all up to this point~~~~~~~~~~~~~~~~~~~~

What is Alzheimer's
http://www.alz.org/alzheimers_disease_what_is_alzheimers.asp

*PRETTY GOOD ONE WITH BASIC/OVERALL INFORMATION**
basics of alzheimer’s disease What it is and what you can do
http://www.alz.org/national/documents/brochure_basicsofalz_low.pdf

*Conclusion*
-Make sure to address testing options for higher risk factors
-Make sure to address questions being addressed right now for the genetics of AD

PAPER

A Closer Look at the Genetics of Alzheimer’s disease; Focusing on APEO Alleles
Eva Mattox and Alex Weborg
Alzheimer’s disease (AD) is a brain affliction that was discovered by a German doctor, Alois Alzheimer in 1906 (*source here?* http://www.alz.org/alzheimers_disease_what_is_alzheimers.asp). Since then scientists have learned a great deal about the disease including symptoms, warning signs, treatments and potential genetic origins. Alzheimer’s is the sixth-leading cause of death in the United States and the most common form of dementia.
This disease is depicted by the formation of amyloid plaques and neurofibrillary tangles which

Alzheimer’s disease (AD) is a neurodegenerative disorder that usually affects individuals over 60 years of age and steadily increasing as the individual ages. (1) It is also irreversible, progressive brain diseases that slowly impares the cognitive skills and memory. (2) There are two types of AD which are early-onset and late-onset. (3) Early-onset AD has found a risk factor to deal with the є2 allele while the late-onset AD has found that the є4 allele of the apolipoprotein E gene (APOE) has been a genetic risk factor in many studies. (4)
є4
The APOE є4 has a more specific risk on late-onset AD and tends to be more pronounced in men than women. (4) The Kungsholmen project gave a specific equation in order to estimate the potential contribution of APOE є4 allele to AD which is called the population attributable risk percentage. (4) PAR%={p(r-1)/[1+p(r-1)]} where p is the proportion of є4 allele in the population and r is the relative risk estimated from another multiple model. Numerous studies have reported that the APOE є4 allele specific risk for Alzheimer’s disease increases with age until around 70 and declines after that. (4)

Є2
A few population studies have noted that the association between the є2 allele and a decrease risk in AD. (4) Subjects that had the є2 allele were found to have a lower risk of dementia. (4)


The Aβ has many plaques that are arranged into high β-pleated sheet fibrils. (6)
Diagnosis
The diagnosis of AD required gradual onset, progressive deterioration, and lack of any other specific causes of dementia. (4)

Random (mice experiment)
Poorly lapidated apoE is highly amyloidogenic. (6) The role of apoE in the aggregation, deposition, and conformation of Aβ in the brain in vivo was first shown when APP Tg mice were crossed to apoe-/- mice. The mice strongly argue the effect of ABCA1 on Aβ related pathology is via altering properties of apoE. It is possible the highly libidated apoE may increase Aβ transport from brain to blood to decrease the probability of Aβ aggregation.
Conclusion Stuff
These mutations on the chromosomal region may increase or decrease the risks of AD. But in order to better understand this disease it is required to get a larger sample size with increased genetic resolution in the region. (5)

References
Risk and Protective Effects of the APOE gene towards Alzheimer’s Disease in the Kungsholmen Project: Variation by Age and Sex. Qui, C., Kivipelto, M., Aguero-Torres, H., Winblad, B., Fratiglioni, L. J Neurol Psychiatry 2004; 75: 828-833.
A Cladistic Analysis of Phenotypic Associations with Haplotypes Inferred from Restriction Endonuclease Mapping or DNA Sequencing. V. Analysis of Case/Control Sampling Designs: Alzheimer’s Disease and the Apoprotein E Locus. Templeton, A.R. Genetics Society of America.
Protein Aggregation in the Brain: The Molecular Basis for Alzheimer’s and Parkinson’s Diseases. Irvine, G.B., El-Agnaf, O.M., Shankar, G.M., Walsh, D.M. Molmed.
Rapid Cognitive Improvement in Alzheimer’s Disease Following Perispinal Etanercept Administration. Tobinick, E.L., Gross, H. Journal of Neuroinflammation. 2008, 5:2.
Genetic (Inherited) Factors. Fisher Center for Alzheimer’s Research Foundation.
Alzheimer’s Disease Genetics; Fact Sheet. Alzheimer’s Disease Education & Referral Center; NAI.
Genetics, Transcripitomics and Proteomics of Alzheimer’s Disease. Papassotiropoulus, A., Fountoulakis, M., Dunckley, T., Stephan, D.A., Reiman, E.M. Journal of Clinical Psychiatry.
Reversal of Alzheimer’s Symptoms Within Minutes In Human Study. Science Daily. Jan. 9,2008.
APOE Promotes the Proteolytic Degradation of Aβ. Jiang, Q., Lee, C.Y.D., Mandrekar, S., et. al. PMC; Neuron. 2008 June 12; 58(5): 681-693.
Identification of Novel Genes that Modify Phenotypes Induced by Alzheimer’s β-Amyloid Overexpression in Drosophila. Cao, W., Song, H., Gangi, T., Kelkar, T., Antani, I., Garza, D., Konsolaki, M. Genetics Society of America 178: 1457-1471, March 2008.
APOE Isoform-Specific Disruption of Amyloid β Peptide Clearance from Mouse Brain. Deane, R., Sagare, A., Hamm, K., Parisi, M., Lane, S., Finn, M.B., Holtzman, D.M., Zlokovic, B.V. Journal of Clinical Investigations.
Overexpression of ABCA1 Reduces Amyloid Deposition in the PDAPP Mouse Model of Alzheimer’s Disease. Wahrle, S.E, Jiang, H., et. al. Journal of Clinical Investigation.

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