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For the first time, scientists have been able to detect signs of Alzheimer’s disease 10 to 20 years before the onset of dementia. The study, presented Wednesday at the Alzheimer’s Association International Conference in Paris, focused on people with rare, inherited forms of the disease who develop it relatively young, with symptoms beginning in the patients’ 30s, 40s, and 50s. Researchers say the results will help them test drugs that could prevent or slow the progression of the disease, not only in these groups, but also in people with the more common late-onset variety.

It’s proven to be extremely difficult to develop effective treatments for Alzheimer’s. One possible reason is that new drugs are tested too late in the progression of the disease; by the time memory problems become evident, extensive brain damage has already taken place. In the last few years, scientists have renewed efforts to find ways to detect the disease earlier, including brain imaging, blood tests, and tests of cerebral spinal fluid (CSF).

Randall Bateman, a neurologist at Washington University School of Medicine, and collaborators have been searching for such predictors by studying families with inherited versions of Alzheimer’s. In these cases, a single copy of the mutated gene guarantees that the carrier will develop the disease. Scientists can estimate the age of the disease’s onset based on the affected parent; that allows them to look for physiological changes decades before memory impairments become evident. The research is part of a large, multicountry study called DIAN (for Dominantly Inherited Alzheimer’s Network).

While this type of Alzheimer’s is rare, accounting for about 1 percent of cases, both inherited and more common “sporadic” forms of the disease are characterized by excessive buildup of amyloid protein in the brain. (The mutations that cause early-onset Alzheimer’s are different from those that increase the risk of developing the disease.)

“We can see changes over time, which allows us to estimate the order and magnitude of changes that occur leading up to Alzheimer’s,” says Bateman. “This is a way to tell us potentially how long of a window we have to treat it, and how we can use these markers in sporadic disease if the timing is the same.”

Families in the DIAN study have mutations in three different genes, all of which are linked to the production or processing of amyloid. Researchers found that family members who carried the disease gene showed an increase amyloid beta protein in the blood and CSF about 30 years prior to the expected onset of the disease compared to noncarrier family members. Within 10 to 15 years of the expected onset, that high level dropped to lower than noncarriers, while levels of tau, another protein associated with the disease, increased. The results come from the analysis of 150 family members with no outward symptoms and an average age of 37.

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Credit: Journal of Neuroscience

Tagged: Biomedicine, Alzheimer's, brain imaging, prediction markets

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