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Could a blood test provide early prediction of Alzheimer’s progression?

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Researchers have demonstrated that a blood test could predict inherited Alzheimer’s disease (AD), over a decade before the clinical symptoms appear. These results give hope that the test could become part of routine medical check-ups, providing a cheap and efficient early warning system for AD.

It is believed that AD takes 10–20 years of slow neurodegeneration before clinical symptoms begins to appear, providing a window of opportunity in which preventative treatments could be most effective. The Dominantly Inherited Alzheimer’s Network (DIAN) study, published in Nature Medicine, describe a new blood test that detects a blood-based protein biomarker called neurofilament light (NfL) that is released into an individuals bloodstream as a result of brain cell damage.

“Normally, such proteins are rapidly degraded in the blood and are therefore not very suitable as markers for a neurodegenerative disease,” explained Mathias Jucker, German Center for Neurodegenerative Diseases (Tübingen, Germany). “An exception, however, is a small piece of so-called neurofilament that is surprisingly resistant to this degradation.”

Data from 405 individuals revealed a correlation between rising NfL levels and the onset of clinical AD symptoms. Interestingly, this becomes clearer as patients converted from pre-symptomatic disease to having clear cognitive and memory decline as NfL builds up in the blood at a faster rate. This suggests that there is no absolute NfL level to indicate the onset of AD but instead increasing rate of change is the vital factor, and biomarkers should be tracked over several years of blood testing for the most accurate diagnosis.

“NfL levels rise whenever the brain is damaged, and as AD affects 30% of people over the age of 80, we hope that NfL will become part of a GP’s standard battery, like annual cholesterol testing,” commented Colin Masters, The Florey Institute (Sheffield, UK). “We would send patients off for more specific Alzheimer’s tests if the results come back showing a cause for concern.”

One limitation of the study is that the results are only relevant to patients with a rare familial risk of developing AD and not the more common sporadic AD. Another concern is that NfL levels can be influenced by other age-related neurodegenerative conditions suggesting the test could be less effective for older patients than younger patients at risk of early-onset dementia. Looking forward, the test will need to be replicated in sporadic AD patients, who are older and often have other health issues.

“I could see this being used in the clinic in a few years to identify signs of brain damage in individual patients. We’re not at the point we can tell people, ‘In 5 years you’ll have dementia’. We are all working towards that,” concluded Brian Gordon, Mallinckrodt Institute of Radiology (MO, USA).

Sources: Preische O, Schultz SA, Apel A et al. Serum neurofilament dynamics predicts neurodegeneration and clinical progression in presymptomatic Alzheimer’s disease. Nat. Med. (2019); www.scimex.org/newsfeed/blood-test-predicts-genetic-alzheimers-disease-progression; https://medicine.wustl.edu/news/blood-test-detects-alzheimers-damage-before-symptoms/

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