Genetic biomarkers may spotlight Alzheimer's years ahead of symptoms

Courtesy Indiana U. School of Medicine

As investigators focused on Alzheimer's try to address the disease as early as possible, new research on a prime biomarker for the disease helps shed some light on early indications of developing cases--as well as just how devilishly difficult this field is.

Working with data collected as part of the national Alzheimer's Disease Neuroimaging Initiative, investigators at Indiana University School of Medicine determined that a variant of APOE--ε4--could be linked at an early point to increased levels of amyloid plaque, clusters of toxic protein believed by many to be a cause of the disease. There were also increased levels of tau--another culprit--as well as signs that the brain was recruiting a precursor of amyloid to help spur new clusters.

What they didn't find were reduced levels of glucose metabolism and brain atrophy, two markers for late-stage disease.

Shannon Risacher, an assistant professor of radiology and imaging sciences, and Andrew Saykin, director of the Indiana Alzheimer Disease Center and IU Center for Neuroimaging, note that it's important to identify biological processes that are occurring years before symptoms of the disease begin to appear.

"These are the individuals who are the logical target for the next wave of clinical trials," said Saykin, who also leads the ADNI Genetics Core. "There are many potential interventions, and not only on the pharmaceutical side. There are intensive studies now of exercise, diet modification, cognitive stimulation, sleep and other lifestyle factors that could lead to an improvement."

But the investigators also note just how difficult this field is.

APOE ε4 has already been linked to an increased risk of developing Alzheimer's disease among older people, but not all Alzheimer's patients have APOE ε4 alleles, or variants "and not all those who do will develop Alzheimer's disease. APOE ε4 is common, found in about 25% of the population. Patients with Alzheimer's disease who also have APOE ε4 tend to have an earlier age of onset of symptoms."

But step by step, investigators continue to hammer away at the challenge, looking to guide a new generation of drugs that could make a difference.

- here's the release

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