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Study Shows Genetic Alzheimer's Detectable 20 Years Before Onset

An inherited form of Alzheimer's disease is likely detectable up to 20 years before loss of memory and impaired thinking appear, according to a study released Wednesday.

Measurable changes in brain chemistry show up years before these signature symptoms of the degenerative brain disease set in, researchers reported at the Alzheimer's Association International Conference in Paris.

The findings only apply to a small fraction -- less than one percent -- of Alzheimer's patients afflicted with a rare variant that generally strikes at a comparatively young age.

But the ability to identify early chemical warning signs in the brain holds out the prospect of preventative treatment not just for these patients, but possibly those struck with more common forms of Alzheimer's as well, the researchers said.

"We want to prevent damage and loss of brain cells by intervening early in the disease process, even before outward symptoms are evident because by then it may be too late," said lead research Randall Bateman, a professor at Washington University School of Medicine.

The type of Alzheimer's examined in the study arises from a genetic mutation that guarantees a person will develop the disease, even if only one parent transmits it.

In the vast majority of Alzheimer's cases, however, the disease arises through a complex interaction of genetic and environmental factors that remains poorly understood.

Worldwide, more than 35 million people are afflicted with the full spectrum of the disease's variants, a figure that is expected to triple by mid-century as populations age.

For the new study, Bateman and colleagues analyzed data from a battery of tests given to carriers of the rare mutation.

The same tests -- cognitive evaluations, positron emission tomography (PET) and magnetic resonance imaging (MRI) scans, searches for telltale markers in cerebro-spinal fluid and blood -- were also done on siblings who did not carry the fateful genetic variant.

Participants destined to develop Alzheimer's not yet exhibiting symptoms were mostly in their mid-to-late 30s, while those who did show the first signs of the disease were in their mid-40s, the age at which the genetic form usually sets in.

Because the disease is so rare, the data had to be gathered by an international network of 11 research centers in the United States, Britain and Australia, known as the Dominantly Inherited Alzheimer Network, or DIAN.

Researchers presented results in Paris for the first 150 volunteers enrolled in the program, which will eventually include 250 more subjects, they said.

The study looked, in particular, for signature changes in brain chemistry related to two kinds of proteins, common to all forms of Alzheimer's.

One is a decreased level in spinal fluid of a protein called amyloid-beta42. Conversely, this indicates a dangerous build up of the same protein in some areas of the brain that ultimately destroys neurons and leads to irreversible brain damage.

The other marker was an increase in tau, the main component of the neuro-fiber tangles that also contribute to cell death.

As suspected, the DIAN subjects in their 30s who carried the genetic mutation showed both characteristics, whereas their non-carrying siblings did not.

"This suggests that we can measure brain chemistry abnormalities in the Alzheimer's gene carriers that begin at least 10 years, maybe even 20 years, before the age that their parents saw Alzheimer's symptoms and when they too would be expected to see them," Bateman said.

The results had broader implications for the treatment of the disease, noted William Thies, Chief Medical and Scientific Officer of the Alzheimer's Association.

"We believe we can learn a great deal more about the vast majority of people whose Alzheimer's develops as a result of complex interactions among their genes, life experiences and other factors," he said.

"Early detection and treatment are crucial if we are to curb the growing epidemic."

Source: Agence France Presse


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