Noninvasive Biomarkers of AD Will Soon Be Reality

Richard S. Isaacson, MD


March 23, 2018

Hi. I am Dr Richard Isaacson, a neurologist and director of the Alzheimer's Prevention Clinic at Weill Cornell Medicine and NewYork-Presbyterian Hospital in New York City.

You may have heard the news about a new blood test that can actually predict whether or not a person has amyloid in the brain. Wouldn't it be great if we could use something simple like a blood test to actually know whether a person is exhibiting symptoms of Alzheimer's disease (AD) rather than a different dementia or another medical condition?

Most people in clinical practice, including myself, rely on the simple things to diagnose AD—the clinical history, for example. If the patient comes in and reports a slowly progressive cognitive decline, most specifically with short-term memory and maybe changes in sleep or mood that are progressive over time, we will rule out a thyroid or B12 deficiency and other typical medical causes, and we use MRI or CT to make sure nothing funny is going on in the brain. Common things happen commonly; progressive short-term memory loss in an older person, especially a person with a family history, is most likely to be AD. However, this is not always the case.

Thus, everyone is looking for that one test that can prove whether or not a person has AD, to stratify that person and help decide whether to recommend a clinical trial or an FDA-approved drug for AD. Now we have a blood test. In February, a study was published in the journal Nature[1] from an excellent team of scientists from Japan and Australia. The goal was to correlate the presence of amyloid in the blood of participants with the presence of amyloid in their brains. The results were fascinating and very promising.

Currently, we do not have a perfect blood test. But you also may have heard about a recent study evaluating a saliva test.[2] Could we do a simple saliva test using proteomics or metabolomics? Actually, maybe we could. That is being hashed out as we speak. We are looking for a test that is simple and noninvasive. What about an eye test? Another recent study used a dye in the eye to see whether amyloid can be viewed on an eye exam.[3]

The field is moving toward using noninvasive clinical tests to predict whether or not a person has AD and then to figure out the most appropriate treatment for that person. Treatment for AD is pretty straightforward. Prevention of AD is much more exciting. A recent study[4] from the University of California, Los Angeles, showed that approximately 47 million Americans are walking around with no symptoms but have AD brain pathology or preclinical, presymptomatic, stage 1 AD.

What if a simple blood, eye, or saliva test could predict that a given person would develop symptoms in the future? We would probably get that person into an AD prevention clinical trial. Believe it or not, several AD prevention clinical trials are ongoing right now using a variety of drugs. Several other trials are looking at prevention in different subsets of people. For a person at higher risk who has two copies of the APOE4 gene, there is a clinical trial specifically for that person.

Using biomarkers that are noninvasive will be extremely important for the treatment of AD as well as the prevention of AD in the future.

For Medscape, I am Dr Richard Isaacson.


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