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Biomarkers that may help check early Alzheimer's identified
19 Jul 2008, 1344 Hrs

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Washington, July 19 (ANI): Researchers from University of California, Los Angeles have identified certain biomarkers that may help check early onset of Alzheimer's in the elderly.

A team led by UCLA associate professor of neurology John Ringman have revealed that levels of specific proteins in the blood and spinal fluid begin to drop as the disease progresses, making them potentially useful as biomarkers to identify and track progression long before symptoms appear.

Familial Alzheimer's and sporadic Alzheimer's are two of the basic types of the disease.

The majority of Alzheimer's cases are sporadic and late-onset, developing after the age of 65 but the cause of this disease is not completely understood.

Familial Alzheimer's (FAD) is a rare form of the disease caused by certain gene mutations that affects less than 2 percent of Alzheimer's patients. FAD is early-onset, meaning the disease develops before age 65, and it is inherited; all offspring in the same generation have a 50-50 chance of developing FAD if one of their parents had it.

The biomarkers that the researchers studied came from patients with FAD mutations.

"Since we knew that 50 percent of first-degree relatives will inherit the same rare mutations, we were able to study the biochemical changes occurring in the cerebrospinal fluid and blood as long as 30 years before the subjects were likely to develop the disease themselves," said Ringman, who is the assistant director of the Mary S. Easton Center for Alzheimer's Disease Research at UCLA.

"This allowed us to identify markers that might be used to diagnose the disease prior to the development of overt symptoms, and also tells us a lot about the chain of events that cause the disease," he added.

During the study the research team looked at several proteins that exist in the cerebrospinal fluid and plasma in 21 FAD mutation carriers and compared them to noncarriers.

Since extracellular plaques characteristic of Alzheimer's that form in the brain consist largely of a fibrous beta-amyloid protein called AB42, the researchers looked at that protein and found that it was elevated in the plasma of FAD mutation carriers, appearing long before the development of obvious dementia.

The level then appears to drop as the disease progresses. Moreover the ratio of AB42 to another protein, AB40, was reduced in the cerebrospinal fluid of FAD mutation carriers and, further, that the levels of two other proteins, called t-tau and p-tau181, were elevated prior to the symptoms.

"The presence of cerebrospinal fluid biomarkers of Alzheimer's disease prior to any clinical symptoms suggests the pathology of Alzheimer's precedes the clinical symptoms and further demonstrates that it may be possible to detect those changes prior to the appearance of cognitive dysfunction," said Ringman.

The study appears in the current issue of the journal Neurology. (ANI)




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