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Researchers Identify Plasma Biomarkers for Alzheimer’s Disease

Promising early indications for an Alzheimer's blood test.

Readers who follow Alzheimer’s disease research closely will know that the FDA hasn’t approved a new treatment in 15 years. A study published this week brings us one step closer to hopefully discovering new screening tools for Alzheimer’s so that patients can be treated early enough to make a difference.

A collaborative effort by scientists and doctors from 11 different universities and hospitals in Japan and Australia has identified a series of plasma biomarkers that could help detect and monitor Alzheimer’s disease. In a study published in Nature, the researchers found that ratios of certain amyloid-? (A?) proteins and their composites served to predict A? burden in the brain, which is thought to be a key factor in Alzheimer’s disease.

According to Adam Bonislawski of GenomeWeb, the results bolster previous findings that similarly demonstrated the potential of plasma markers for assessing brain A? levels and suggest that blood-based markers could prove useful for screening people for the disease, particularly in the context of trials looking at Alzheimer’s drugs and prevention.

The researchers measured levels of three different protein markers (APP669-711, an A? precursor protein, and A?40 and A?42, A? protein fragments) in a discovery set of 121 Japanese patients and a validation set of 252 Australian patients. Both sets included a mix of cognitively normal individuals, subjects with mild cognitive impairment, and subjects with clinically diagnosed Alzheimer’s disease with dementia. A composite marker corresponding to brain A? levels as assessed by positron emission tomography (PET) and cerebrospinal fluid (CSF) measurements.

All test biomarkers showed high performance when predicting brain amyloid-? burden. In particular, the composite biomarker showed very high areas under the receiver operating characteristic curves (AUCs) in both data sets (discovery, 96.7%, n = 121 and validation, 94.1%, n = 111) with an accuracy approximately equal to 90% when using PIB-PET (Pittsburgh compound B PET) as a standard of truth. Furthermore, test biomarkers were correlated with amyloid-?-PET burden and levels of A?1–42 in cerebrospinal fluid. These results demonstrate the potential clinical utility of plasma biomarkers in predicting brain amyloid-? burden at an individual level. These plasma biomarkers also have cost–benefit and scalability advantages over current techniques, potentially enabling broader clinical access and efficient population screening.

– Katsuhiko Yanagisawa, director general of Japan’s National Center for Geriatrics and Gerontology Research Institute and senior author on the study.

Dr. Yanagisawa said he and his colleagues hoped to develop the assay as a tool for screening patients for Alzheimer’s drug trials. This is a major goal of Alzheimer’s biomarker development work due to the challenges of identifying patients at risk for the disease who may benefit from treatment.

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