Senior Citizens’ Greatest Fear – Alzheimer’s – More Likely if Both Parents Have It

Risk of AD increased with age – affected 31% of those over age 60

March 10, 2008 - When it comes to disease, most Americans fear cancer the most, but not senior citizens. Many older people have witnessed the damage of brain-killing Alzheimer’s Disease in a friend or relative and it has become their number one fear. New research out today says adults whose parents - both parents - are AD victims appear to have as high as almost four times the risk of developing the disease.

“The majority of AD cases are late-onset, usually developing after age 65. Late-onset AD has no known cause and shows no obvious inheritance pattern, according to the National Institute on Aging.

	Related Stories
	SORL1 Gene Becomes Second Firmly Linked with Late-Onset Alzheimer’s Joins ApoE4 in list of key suspects for devastating disease Oct. 30, 2007 Alzheimer's, Parkinson's, Diabetes, Mad Cow Similar at Molecular Level Protein analysis may offer new diagnoses and treatment options April 30, 2007 New Gene Variant Found in Senior Citizens with Alzheimer's Disease SORL1 joins ApoE4 as genetic variant for late-onset Alzheimer's January 15, 2007 Senior Citizens Appear to Have Exclusive Claim on Alzheimer’s Disease Boomers, young adults thinking they have AD are probably wrong - higher risk with APOE4 gene January 8, 2007 Cold Sore Virus Suspected of a Role in Causing Alzheimer's Disease ApoE-4 gene, leading risk factor of Alzheimer's in senior citizens, linked with herpes January 3, 2007 Genetics Used to Learn How People Reach 90 with Good Mental Ability August 10, 2006 Researchers Uncover Genetic Clues to a Common Form of Age-Related Dementia Dementia with Lewy bodies is second most common after Alzheimer's July 17, 2006 New Genetic Cause of Alzheimer's Found Study says quantity of amyloid protein is key to early dementia April 19,2006 Clear Genetic Link Found for Alzheimer's in Study of Twins Genetics also play a role in the timing of the disease Feb. 6, 2006 Severe Alzheimer’s Reversed in Mice through Gene Therapy Sept. 21, 2005 Older People With the "Alzheimer's Gene" Find It Harder to "Remember to Remember" Jan. 24, 2005 Gene Vaccine for Alzheimer’s Shows Promising Results Dec. 14, 2004 New genetic risk factor for susceptibility to Alzheimer's disease is found  6/19/1 Read the latest news on Alzheimer's, Dementia & Mental Health

“However, in some families, clusters of cases are seen. Although a specific gene has not been identified as the cause of late-onset AD, genetic factors do appear to play a role in the development of this form of AD. Only one risk factor gene has been identified so far.” (Read more by NIA below this news report.)

The researchers, reporting in the March issue of Archives of Neurology, one of the JAMA/Archives journals, point out that AD is a common cause of dementia and the leading cause of cognitive-impairment in the U.S. elderly population.

"Because Alzheimer's disease is so common in the general population, it is not uncommon for both spouses to develop the disease,” they write. “Offspring of two such affected individuals would presumably carry a higher burden of these Alzheimer's disease-associated genes."

Older Americans Fear Alzheimer's the Most, While Most Adults Fear Cancer MetLife survey finds little planning for Alzheimer’s disease May 31, 2006 – Most Americans fear cancer the most and Alzheimer's disease second, but this flips for those age 55 and older, where Alzheimer's is the disease they most fear, according to a report issued this month - “MetLife Foundation Alzheimer’s Survey: What America Thinks,” conducted by Harris Interactive. Read more...

Suman Jayadev, M.D., of the University of Washington, Seattle, and colleagues studied the frequency of Alzheimer's disease in adult children of 111 families in which both parents had been clinically diagnosed with the disease. Ages at onset of dementia were also noted.

Of the 297 offspring who reached adulthood, 22.6 percent developed Alzheimer's disease compared with an estimated 6 percent to 13 percent of the general population.

The average age at onset for children of couples with the illness was 66.3.

The risk of developing the disease increased with age with 31 percent of those older than age 60 affected and 41.8 percent of those older than age 70 affected.

"Of the 240 unaffected individuals, 189 (78.8 percent) had not yet reached age 70 years, suggesting that the incidence of Alzheimer's disease (22.6 percent) is an underestimation of the final incidence rate of Alzheimer's disease in this population," the authors write.

Having additional family members with Alzheimer's disease did not increase the risk of developing the disease, but was associated with a younger age at onset for those who did develop the illness.

Children with no history of the disease beyond the parents had an older age at onset (72 years) compared with those who had one parent with family history of the disease (60 years) or both parents with family history of the illness (57 years).

"The role of family history and the specific genes involved in this phenomenon require a better definition," the authors conclude.

"Families with a significant Alzheimer's disease history may be more likely to be referred to an Alzheimer's disease research center and, thus, the present patients may be 'enriched' for a particularly Alzheimer's disease-prone subgroup. Following these families as the offspring continue to age will provide increasingly informative data."

Editor's Note: This study was supported by grants from the National Institute on Aging/National Institutes of Health and by Veterans Affairs research funds.

The Genetics of Alzheimer's Disease (AD)

By the National Institute on Aging

Scientists do not yet fully understand what causes Alzheimer's disease (AD). However, the more they learn about AD, the more they become aware of the important function genes* play in the development of this devastating disease.

Diseases such as cystic fibrosis, muscular dystrophy, and Huntington's disease are single-gene disorders. If a person inherits the gene that causes one of these disorders, he or she will usually get the disease. AD, on the other hand, is not caused by a single gene. More than one gene mutation can cause AD, and genes on multiple chromosomes are involved.

The two basic types of AD are familial and sporadic.

Familial AD (FAD) is a rare form of AD, affecting less than 10 percent of AD patients. All FAD is early-onset, meaning the disease develops before age 65. It is caused by gene mutations on chromosomes 1, 14, and 21. Even if one of these mutated genes is inherited from a parent, the person will almost always develop early-onset AD.

This inheritance pattern is referred to as autosomal dominant inheritance. In other words, all offspring in the same generation have a 50/50 chance of developing FAD if one of their parents had it.

Genes in Late-onset Disease

The majority of AD cases are late-onset, usually developing after age 65. Late-onset AD has no known cause and shows no obvious inheritance pattern. However, in some families, clusters of cases are seen. Although a specific gene has not been identified as the cause of late-onset AD, genetic factors do appear to play a role in the development of this form of AD. Only one risk factor gene has been identified so far.

Researchers have identified an increased risk of developing late-onset AD related to the apolipoprotein E gene found on chromosome 19. This gene codes for a protein that helps carry cholesterol in the bloodstream. The APOE gene comes in several different forms, or alleles, but three occur most frequently: APOE e2, APOE e3, and APOE e4.

People inherit one APOE allele from each parent. Having one or two copies of the e4 allele increases a person's risk of getting AD. That is, having the e4 allele is a risk factor for AD, but it does not mean that AD is certain. Some people with two copies of the e4 allele (the highest risk group) do not develop clinical signs of Alzheimer's disease, while others with no e4s do. The e3 allele is the most common form found in the general population and may play a neutral role in AD. The rarer e2 allele appears to be associated with a lower risk of AD. The exact degree of risk of AD for any given person cannot be determined based on APOE status. Therefore, the APOE e4 gene is called a risk factor gene for late-onset AD.

Scientists are looking for genetic risk factors for late-onset AD on other chromosomes as well. They think that additional risk factor genes may lie on regions of chromosomes 9, 10, and 12.

The National Institute on Aging (NIA) has launched a major study to discover remaining genetic risk factors for late-onset AD. Geneticists from the NIA's Alzheimer's Disease Centers are working to collect genetic samples from families affected by multiple cases of late-onset AD. Researchers are seeking large families with two or more living relatives with late-onset AD.

Families interested in participating in this study can contact the National Cell Repository for Alzheimer's Disease at 1-800-526-2839.

Information may also be requested through their website, http://ncrad.iu.edu.

>> Read more on Alzheimer’s genetics at the National Institute on Aging