Is this gene causing the Alzheimer's?

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A new study has identified the cause of late-onset Alzheimer's disease in several large families in which many siblings suffer from the disease. The gene, known as TRPC4AP on chromosome 20, is involved with calcium regulation. It is known that when calcium levels are not carefully controlled, cells can die, leading to the onset of disease.

Alzheimer's disease is a complex progressive neurodegenerative disorder in which patients suffer from profound cognitive decline. There is no known cure for the disease, but treatment delays its progression. Its cause is currently unknown, though family history has been identified as an important risk factor. Heritability for the disease has been estimated at 79 percent, with no susceptibility difference found between men and women. Many genetic variants of the disease have been identified; however replication in other samples of Alzheimer's patients has been limited.

In research conducted at the Medical College of Georgia and the VA Medical Center in Augusta, Ga., two large families with late-onset Alzheimer's disease were enrolled in a DNA Bank. Both families had 15 siblings, five of whom were affected with the disease. Moreover, in one family, several of the father's siblings also were affected and were still living, a rarity among study populations of late-onset Alzheimer's patients. Blood samples were collected from all siblings, the parent's siblings, as well as the spouses and children for genetic study.

Dr. Shirley Poduslo and her staff used high-tech SNP microarrays, which display the genetic structure of DNA, with the patients and control spouses to identify the location of the gene causing the disease in these families. SNPs, or single nucleotide polymorphisms, are single base changes in gene structure which are found throughout DNA. Next they analyzed additional SNPs in the DNA from each family member. They found that all of the affected patients from both families had the same pattern of SNPs, which were different from the control spouses. Dr. Poduslo and her lab then analyzed DNA from the Alzheimer's patients and controls in the DNA Bank. They found that 36 percent of the patients had the same pattern of SNPs as found in the patients in the families. "The use of extended pedigrees is vital for genetic studies. The next step will be to identify the exact mutation in this gene which is causing the disease," says Poduslo. "The DNA is currently being sequenced to find this mutation."

These findings have opened a new line of research that may potentially lead to understanding what causes Alzheimer's. Future studies of this protein may potentially lead to new drug treatments. "The long term significance will be to understand the mechanism of the disease so that more effective drugs can be designed to slow the progression of the disease, delay the onset, identify patients early in the disease course and, hopefully, someday to keep this dreadful disease from occurring," says Poduslo. ...http://www.medicalnewstoday.com

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