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Genetic Alteration Predisposes some Hispanics to Early-onset Alzheimer's Disease

  [ 82 votes ]   [ Discuss This Article ] • December 5, 2001

A unique genetic change associated with the development of early-onset Alzheimer's disease in Caribbean Hispanics has been identified by Columbia University College of Physicians & Surgeons researchers. This newly recognized variation in the presenilin 1 gene also seems to trace back to a common ancestor.

The findings, published in the Nov. 14 issue of the Journal of the American Medical Association should allow physicians to use mutation analysis to better diagnose the neurodegenerative disease in certain families of Caribbean Hispanic heritage, and to genetically counsel family members with a familial risk for the disorder.

"This is the first genetic alteration characterized for early-onset Alzheimer's disease in the Caribbean Hispanic population," said Dr. Richard Mayeux, director of the Gertrude H. Sergievsky Center and co-director of the Taub Institute on Alzheimer's Disease. "The mutation should help us diagnose early-onset Alzheimer's disease in this population group. And Caribbean Hispanics under age 60 who have a history of Alzheimer's disease may consider getting screened for this mutation."

Clinicians recognize two types of Alzheimer's disease: familial, in which multiple family members are affected, and sporadic, when only one member in a family has the disease. They further distinguish early-onset Alzheimer's, which affects people between the ages of 30 and 60, and late-onset disease, which is usually diagnosed in people who are at least 65.

Early-onset disease, which accounts for only 10 percent to 15 percent of the cases, is strongly hereditary. Late-onset is the more common form of the disease, which can be both genetic and sporadic.

In the study, the researchers analyzed the DNA of 44 individuals in 19 families of Caribbean Hispanic descent who had been diagnosed with early-onset Alzheimer's disease. They looked for the presence of genetic changes or mutations in two genes, presenilin 1 and amyloid precursor protein.

Scientists already had found an association between early-onset Alzheimer's disease and these two genes in other populations. The investigators focused on Caribbean Hispanics because the frequency of Alzheimer's disease is higher among Hispanics in general and in this population in particular, compared with non-Hispanic whites. Columbia researchers reported the increased risk of Alzheimer's disease among Caribbean Hispanics earlier this year in Neurology.

"But Caribbean Hispanic families have not typically been included in comprehensive studies of the genetic determinants of early-onset Alzheimer's disease," Dr. Mayeux says.
The investigators performed the genetic analysis on families living in Northern Manhattan, many of whom emigrated from the Dominican Republic to the United States, and on families currently living in the Dominican Republic.

They found 18 unrelated families had the exact same genetic mutation at a specific location in the presenilin 1 gene. The mutation results in the amino acid alanine to be put into the presenilin protein instead of glycine.

Experiments with cultured cells containing the mutated gene revealed the alteration causes an increase in the expression of the toxic form of beta amyloid, a substance usually found in the brains of Alzheimer's patients. The researchers also found that all the families shared certain unique genetic similarities in a region of DNA that flanked the gene, indicating that these families had all shared a common ancestor at some point in history.

Not every Caribbean Hispanic family with early-onset Alzheimer's disease in the study had the mutation, however. The Columbia researchers currently are screening more than 200 Caribbean Hispanic families that have at least two individuals affected by all types of Alzheimer's disease for a wide range of genetic markers. One or several of these may someday be shown to be associated with the devastating disease in this population and in others.

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