Genetic Testing for Alzheimer's Disease
DESCRIPTION
Alzheimer's disease (AD) affects approximately 4 million Americans. It is the leading cause of dementia and the fourth leading cause of death among people aged 65 years and older. The lifetime risk of Alzheimer's disease in the general population is estimated to be between nine and fifteen percent. Forty percent of individuals with Alzheimer's disease have at least one first-degree relative who also has the disease.
AD can be broken into two categories, late-onset and early-onset. Late-onset AD usually occurs after age 60 and is attributed to more than ninety percent of occurrences. It usually lasts longer than ten years and results in limited physical deterioration. Early-onset AD usually appears before age 60 and is less common. It usually results in a rapid decline with severe neurochemical and neuropathological changes.
Evidence seems to indicate that early-onset AD is associated with mutations in one of three genes: presenilin 1 (PS1) on chromosome 14, presenilin 2 (PS2) on chromosome 1, or amyloid precursor protein (APP) on chromosome 21. Together, these mutations may be responsible for thirty to fifty percent of the episodes of autosomal dominant AD and for approximately five percent of AD in general.
The more common late-onset form of AD may be associated with the presence of an apolipoprotein E (APOE) epsilon 4 allele found on chromosome 19. The three principle types of apolipoproteins in humans are epsilon 2, epsilon 3, and epsilon 4. These allele frequencies vary among ethnic groups. Among Caucasians, the allele frequency for epsilon 4 is fifteen percent. Among African-Americans, the frequency of the epsilon 4 allele is approximately nineteen percent. The presence of at least one epsilon 4 allele is associated with an increased risk of AD. For those homozygous for epsilon 4, the risk of AD is higher than for those that are heterozygous. About two percent of the population is homozygous for the epsilon 4 allele.
POLICY
Genetic testing for PS1, PS2 or APP gene mutations for the diagnosis or prediction of risk of Alzheimer's disease is considered investigational.
Genetic testing for the apolipoprotein E (APOE) epsilon 4 allele for the diagnosis of Alzheimer's disease is considered investigational.
Genetic testing for the apolipoprotein E (APOE) epsilon 4 allele in asymptomatic individuals is considered investigational.
See also: Biochemical Markers for Alzheimer’s Disease
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ADDITIONAL INFORMATION
Scientific evidence is not available to show that genetic testing for Alzheimer's disease can predict clinical events and therefore it has not been proven to be effective to alter treatment.
Other diagnostic tests for Alzheimer's disease include cerebrospinal (CSF) fluid biomarkers of the Tau protein or beta-amyloid precursor protein. Genetic testing for Alzheimer's disease may be performed along with the above-mentioned CSF tests. This group of tests may be collectively referred to as the ADmark™ Profile and is offered by Athena Diagnostic of Worcester, MA. This policy does not address the biomarkers for AD.
SOURCES
Alzheimer’s Association. (2008, April). Position statement on genetic testing. Retrieved June 13, 2008 from http://www.alz.org/national/documents/statements_genetictesting.pdf.
BlueCross BlueShield Association. Medical Policy Reference Manual. (12:2009). Genetic testing for familial Alzheimer's disease (2.04.13). Retrieved September 21, 2011 from BlueWeb. (14 articles and/or guidelines)
Goldman, J., Hahn, S., Catania, J., LaRusse-Eckert, S., Butson, M., Rumbaugh, M., et al. (2011) Gentic counseling and testing for Alzheimer’s disease: Joint practice guidelines of the American College of Medical Genetics and the National Society of Genetic Counselors. Genetics in Medicine, 13 (6), 597- 605.
Hort, J., O’Brien, J., Gainotti, G., Pirtilla, T., Popescu, B., Rektorova, I., et al. (2010) EFNS guidelines for the diagnosis and management of Alzheimer’s disease. European Journal of Neurology, 17 (10), 1236-1248.
Perry, R. T., Gearhart, D. A., Wiener, H. W., Harrell, L. E., Barton, J. C., Kutlar, A., et al. (2008). Hemoglobin binding to A beta and HBG2 SNP association suggest a role in Alzheimer's disease. Neurobiology of Aging, 29 (2), 185-193.
Third Canadian Consensus Conference on Diagnosis and Treatment of Dementia. (2007) Retrieved July 12, 2011 from http://www.cccdtd.ca/pdfs/Final_Recommendations_CCCDTD_2007.pdf.
U. S. Department of Health and Human Services. Public Health Service. U. S. National Institute of Health. National Institute on Aging. (2008, November). Alzheimer’s disease genetics fact sheet. Retrieved December 30, 2009 from http://www.nia.nih.gov/Alzheimers/Publications/geneticsfs.htm.
ORIGINAL EFFECTIVE DATE: 9/13/1999
MOST RECENT REVIEW DATE: 11/10/2011
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