In 2016, 5.4 million Americans were living with Alzheimer’s disease (AD), and a large majority of those people are over the age of 65. AD can often be difficult to distinguish from other types of dementia, which makes it hard for physicians to diagnose confidently even though it is is the most common type of dementia, accounting for 50-70 percent of total patients. The predicated rise in AD occurrence, in correlation with the rapidly aging population in the United States, is forcing the scientific and medical communities to take a closer look at more efficient and reliable ways to diagnose and manage AD.
Today there are three main methods through which Alzheimer’s disease can be detected and diagnosed. Traditional methods utilize brain-imaging studies like magnetic resonance imaging (MRI) and positron emission tomography (PET) scans. The major problem with these methods is that significant structural changes to the brain do not occur until the late stages of the disease when diagnosis is less helpful for the long-term prognosis of the patient. The most reliable method for AD diagnosis is through biomarkers detected in the cerebrospinal fluid (CSF). Proteins in the CSF derive from the brain itself. As a result the identified CSF biomarkers correlate with plaque pathology, neuroaxonal degeneration, and neurofibrillary tangle pathology in the brain, which all reflect the progression of AD. However, diagnosis through CSF is a very invasive process for the patient and requires expensive specialized facilities for the required diagnostic imaging, making it a less than ideal practice.
The inadequacy of PET and MRI scans and the expense and invasiveness of extracting CSF has spurred a growing interest in discovering and standardizing blood-based biomarkers for AD. If determined effective, plasma biomarkers would represent a less expensive, less invasive, and more efficient alternative to working with CSF biomarkers. Because of these benefits, identifying reliable blood biomarkers for AD is being given a very high priority in the bioanalytical community.
The challenge in defining a reliable protein biomarker in blood is that there are tens of thousands of different proteins housed in blood plasma. Interestingly, the widely accepted CSF biomarker shows up in blood tests, but at a significantly diluted level, making it almost impossible to detect among the mass of other proteins. Instead of attempting to utilize the CSF biomarkers in blood, scientists recently defined a new plasma protein biomarker called clusterin. Clusterin is involved with the clearance of cellular debris and apoptosis and has a positive correlation with the risk of conversion to AD as well as with cognitive decline. There are promising results utilizing clusterin as a biomarker in this context, and studies have been detecting AD with about 90% accuracy.
For other disease states biomarkers are generally employed to detect a process indicating the onset of a particular disease. Today no single biomarker is able to definitively accomplish this for AD. AD is a long and drawn out disease and has many different stages and different biomarkers may be more apparent than others at different points in the disease’s progression. As I see it, as we move forward in the study of reliable AD biomarkers it will be imperative to determine when in the disease lifecycle specific biomarkers need to be measured to provide the most effective treatment.
If the identification of a reliable AD biomarker can be accomplished, blood testing for measuring AD biomarkers will likely outpace the use of CSF testing and even the long-enduring MRI and PET scans. We can arrive at this destination more quickly through collaboration between groups of innovative scientists committed to increasing the availability and creation of large sample sets of data on which we can base future studies and levels of reliability. If collaborative studies continue to evolve at the rate they are today I predict a major reduction in the fragmentation of data across the industry. I think that it is very likely that we’ll see plasma biomarkers become a new and innovative, yet reliable, indicator for diagnosing AD.
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