Biomarkers Used To Assess Risk of Alzheimer’s Disease Before Symptoms Occur

Biomarkers are defined as a biological marker which indicates that a biological or pathogenic process or pharmacologic response in the body has taken place.

Many diseases that develop over decades, such as cancer and heart disease can be measured and tracked by certain biomarkers. Up until recently, this approach has not been utilized for predicting Alzheimer’s disease.

Scientists are researching the use of blood tests, PET scans, eye tests, genetics and even sniff tests to identify the earliest stages of cognitive decline before symptoms occur.

Cerebrospinal fluid tests may predict Alzheimer’s disease the earliest. This test can reveal the presence of the tau protein up to 30 years before the symptoms of cognitive decline appear and it can also reveal the presence of amyloid beta 10-15 years before symptoms appear.

There are several ongoing clinical studies testing the accuracy of blood tests in predicting cognitive decline and Alzheimer’s disease. The studies focus on detecting the changes in RNA and analyzing and measuring the response in blood samples. This is accomplished by using DNA sequencing technology. These blood tests have proven to be highly accurate in predicting Alzheimer’s disease and will soon be available for use as a screening tool. They detect pathology at a much earlier stage (pre-plaque formation) and will be less expensive, more accessible and less intrusive than current diagnostic and screening tools like PET scans. The hope is that similar to having your cholesterol measured at a regular doctor’s appointment and being prescribed statins for less than optimal numbers, the same approach will be available in the future for Alzheimer’s disease. As with most health care issues, one will be faced with some difficult decisions. Since there is no meaningful treatment currently available for Alzheimer’s disease, some people may not want to know their risk profile. There is also the issue of the conflict between public health and individual choice. I will leave this for future discussion! While the blood test is scheduled to be available in Europe in 2021 and in the U.S. in2022, the following highlights a few interesting clinical studies:

Recently a study conducted in Sweden concluded that the specific biomarkers of Alzheimer’s disease are detectable in blood. The particular biomarker studied is the Neurofilament light (NfL). This protein indicates neuroaxonol injury and is released by the brain neurons when they are damaged or dying and then leaks into cerebrospinal fluid and blood. This study will be useful to monito effects of disease modifying drugs.

Another study completed at the Mayo Clinic set out to evaluate the association between amyloid, tau and neurodegeneration (ATN) biomarker profiles and memory decline. The study concluded that these ATN biomarkers provided “modest but significant” incremental information beyond clinical and genetic information in predicting memory decline.

Another study done at Washington University School of Medicine focused on 158 adults over the age of 50 who were “cognitively normal”. They used mass spectrometry to measure amyloid beta 42 and amyloid beta 40. the ratio of these two forms declines as amyloid deposits in the brain increase. The study participants underwent PET scans which correlated 88% of the time with blood draws.

While so many drugs aimed at removing the amyloid plaques in the brain have failed, it seems as if the approach should shift to looking downstream for the cause of the plaques.

https://newatlas.com/alzheimers-dementia-biomarkers-early-diagnosis/59704/

https://www.ncbinlm.nih.gov/pubmed/3084229

https://www.ncbi.nlm.nih.gov/pubmed/31009028/

https://www.ncbi.nih.gov/pubmed/31371569/

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