Early Detection of Misfolded Amyoid-β in the Blood Implies Greater Risk of Later Alzheimer's Disease

In recent years, a great deal of effort has been put towards means of assessing risk of Alzheimer's disease as early as possible in aging individuals. The results here are an illustrative example of initiatives focused on amyloid-β in the blood: assays based on a blood sample are somewhat easier to develop than most of the other options; amyloid-β levels in the brain are known to increase slowly over time; and the presence of amyloid-β in the brain and bloodstream are in some form of dynamic equilibrium with one another.

There is currently still no effective treatment for Alzheimer's disease. For many experts, this is largely due to the fact that the disease cannot be clinically diagnosed until long after the biological onset of disease when characteristic symptoms such as forgetfulness appear. However, the underlying brain damage may already be advanced and irreversible by this stage. "Everyone is now pinning their hopes on using new treatment approaches during this symptom-free early stage of disease to take preventive steps. In order to conduct studies to test these approaches, we need to identify people who have a particularly high risk of developing Alzheimer's disease."

In patients with Alzheimer's disease, misfolding of the amyloid-β protein may occur 15-20 years before the first clinical symptoms are observed. The misfolded proteins accumulate and form amyloid plaques in the brain. A new technique can determine whether amyloid proteins are misfolded in blood plasma, and researchers have demonstrated that misfolded amyloid-β in the blood correlates with plaque formation in the brain.

Researchers reexamined blood samples collected as part of the ESTHER cohort study, looking at 150 ESTHER participants in whom dementia was subsequently diagnosed during the 14-year follow-up period. These samples were compared with those of 620 randomly selected control participants not known to have been diagnosed with dementia who correlated with the dementia participants in terms of age, sex, and level of education. Participants with amyloid-β misfolding had a 23-fold increased odds of Alzheimer's disease diagnosis within 14 years. In patients with other types of dementia, such as those caused by reduced blood supply to the brain, the study did not demonstrate an increased risk, supporting Alzheimer's disease specificity.

Link: https://www.dkfz.de/en/presse/pressemitteilungen/2019/dkfz-pm-19-46-Protein-misfolding-as-a-risk-marker-for-Alzheimers-disease-up-to-14-years-before-the-diagnosis.php

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