In the Research Article entitled “Blood Biomarkers in Neurodegenerative Diseases: Implications for the Clinical Neurologist,” Dr. Alcolea et al.1 reviewed the medical literature and summarized a large and rapidly expanding area of research: the use of biomarkers in neurodegenerative diseases. These illnesses tend to progress very slowly over time and cause problems with thinking, memory, movement, language, and judgment. In the past few years, there have been great advances in the ability to consistently and accurately detect the abnormal proteins in the blood that occur in certain neurologic illnesses such as Alzheimer disease. These abnormal proteins are known as biomarkers. Biomarkers are measurable substances that signal the presence of an illness.
Biomarkers can be found with many kinds of tests. For instance, an MRI can measure changes in the brain that occur because of Alzheimer disease. These measurable changes, visible in the pictures of the brain taken during an MRI, are one kind of biomarkers. In another type of test, specialized radioactive (do not worry, it is safe) molecules are injected into the bloodstream. This highlights areas where a disease is most active. A measure of that activity is another form of biomarker. Some of these tests are easy to perform and to repeat, such as blood testing. Other tests such as a lumbar puncture (also called a spinal tap) are more difficult to perform and often need to be performed by a specialist. Recent research in Alzheimer disease has focused on testing for the presence of biomarkers in the blood. The reasons for this are simple: blood samples are relatively easy to collect, are minimally invasive, and can easily be used to follow-up an illness over time.
Although it may seem simple, measuring a biomarker of a brain disease can be difficult. This is because the brain is isolated from the blood by a structure called the blood-brain barrier (BBB). There are very few substances that can cross the BBB. This means that very little of the abnormal brain proteins that build up in the brain of a person with an illness such as Alzheimer disease can cross over from the brain into the bloodstream. This is where newer technologies become important. These technologies can measure extremely small quantities of these abnormal proteins in a person's blood.
Certain biomarkers in the blood are specific to Alzheimer disease, such as amyloid-beta (Aβ) and phosphorylated tau (p-tau) proteins. Other biomarkers occur in many neurologic diseases, including Alzheimer disease, but are not specific to Alzheimer disease. These nonspecific biomarkers include proteins such as neurofilament light (NfL) and glial fibrillary acidic protein (GFAP). But whether they are specific to Alzheimer disease or not, biomarkers such as these are known to be present in people who experience symptoms of Alzheimer disease. These symptoms include poor memory or problems with thinking. Scientists have also found these biomarkers in people who currently have no symptoms of Alzheimer disease, but who are at risk of developing it.
There is another challenge to measuring biomarkers in Alzheimer disease: namely, do other illnesses affect the test results? For instance, what if a person with Alzheimer disease also has kidney or liver disease? The kidneys and liver are organs that constantly clear abnormal substances from the blood. So, how might an illness of these organs affect the test results? Little is known about how other common illnesses such as diabetes, high blood pressure, and high cholesterol affect these tests. In addition, researchers have found that different groups of people have different outcomes from these tests. For example, biomarkers tend to be much harder to detect in Black patients than in White patients. Overall, much more research is needed to find out how the results of biomarker tests might differ among diverse patient populations.
Another limitation to current research is this: if these proteins can be detected in people at risk of developing Alzheimer disease, how does this knowledge affect the person themselves? Does it affect their ability to be employed? To obtain health insurance? Does this information affect a person's overall sense of well-being? Will an abnormal test be a motivation to tackle the problem, or will the test results cause anxiety, stress, and depression? To this last point, recent studies have so far shown that knowledge of the presence of biomarkers for Alzheimer disease does not increase a person's anxiety or depression about their condition.
Why Was the Study Conducted?
There has been a flurry of research on the usefulness of biomarkers in detecting neurodegenerative illness. In their study, Dr. Alcolea and colleagues reviewed the medical literature on this topic to crystallize the current thinking about the usefulness of testing for blood-based biomarkers. More specifically, they wanted to know how results from biomarker tests could be helpful to a general neurologist or primary care doctor in treating patients who may have a neurodegenerative condition. The article reviewed different biomarkers that showed promising results in the evaluation of these diseases. The research shown in this study supports the idea that, when performed using current technologies, blood biomarker tests are accurate, easily collected, and can be followed up as frequently as needed to monitor a person's illness.
What Did the Study Show?
The study reviewed the usefulness and effectiveness of blood-based biomarkers in several areas: disease diagnosis, disease progression, and following up a patient's response to treatment. Dr. Alcolea and colleagues discussed the types of biomarkers found in different neurodegenerative diseases. As previously stated, there are 2 major biomarkers for Alzheimer disease: amyloid-beta peptide (Aβ) and phosphorylated-tau protein (p-tau). There are different kinds of Aβ proteins as well. Research has shown that by measuring both types and comparing them, the testing accuracy is higher than when measuring either one alone. P-tau testing has shown high accuracy in detecting Alzheimer disease. Serum NfL biomarkers are less specific to Alzheimer disease and can be found in many other diseases that affect the central and peripheral nervous systems. Glial fibrillary acidic protein is also higher in Alzheimer disease but has been most studied as a biomarker of traumatic brain injury.
Why Is This Study Important?
This review shows how useful blood-based biomarkers could be in a clinical setting. They could be used to identify people at risk of disease, to make diagnosis more accurate, to follow-up disease progression, and to measure patient response to treatment. By identifying patients who are early in the course of their illness, treatment could be started earlier. Because of this, the use of biomarker testing could help prevent people from ever having the serious neurologic problems that occur in advanced Alzheimer disease.
About Alzheimer Disease
What Is Alzheimer Disease?
AD is a neurologic disease that typically affects the brain very slowly and over a long period of time. A gradual loss of memory is one of the main symptoms that a person with AD experiences. However, memory problems are just one of the symptoms of the disease. A person with AD may also have problems with language and changes in behavior, mood, or personality. The loss of neurologic function usually occurs over a period of 5–20 years A person with advanced AD might need help with daily tasks such as eating, grooming, and proper hygiene. In other words, AD is a disease that affects both the patient and their family.
Approximately 4 million people in the United States have AD. It is estimated that more than 360,000 new cases occur in the United States each year. This number will probably increase as the population ages, because aging itself is a major risk factor for the development of AD. AD is the fourth leading cause of death for adults. It kills more than 100,000 Americans each year.2
What Are the Symptoms of Alzheimer Disease?
The diagnosis of AD depends on the identification of specific criteria. Loss of recent memories (also called short-term memory) can be one of the earliest warning signs. For instance, the person might repeat stories in the same conversation. Or they may forget the details of the previous day, such as what they had for breakfast or lunch.
Because AD is gradual, many people with early AD do not realize something is wrong. They may assume that such forgetfulness is “just a sign of getting older.” By itself, forgetting things occasionally is common and is usually not serious. But if it becomes frequent, or if the forgetfulness worsens over time, it may be a sign of a more serious problem. As AD worsens, the person's family may begin to notice that the person can no longer perform their usual daily tasks. Things they performed previously, such as managing finances and paying bills on time, become increasingly difficult. The person may not be “forgetting” to pay the bills but may no longer be able to complete this complex task at all.
How Is Alzheimer Disease Diagnosed?
When AD is suspected, it is important to have a complete medical and neurologic workup. The purpose of this is to uncover the possible causes of the cognitive problems the patient is experiencing to rule out other possible diseases or conditions. An evaluation will include a complete health history and physical examination, screening for depression (which can also cause memory problems), and neurologic and mental status testing. Often, the next step is to obtain blood and urine tests. A picture of the brain from a CT scan or MRI is also helpful in reaching a diagnosis. In some people, more specific tests such as a PET scan or a single photon emission CT may be performed.
What Causes Alzheimer Disease?
Although the abnormalities in the brain that appear with AD are known, the cause of AD itself is not fully understood. It is important to know that AD is not contagious. And although genetic forms have been identified, the most common form of AD does not run in families.
What Are the Treatments?
AD treatment is also a rapidly growing area of research. There are many new treatments for both the symptoms of AD and its underlying cause. If you or a loved one has been diagnosed or is at risk of AD, ask your doctor about the newest treatments available for AD.
In addition to medications and medical treatments, studies have shown ways we can keep our brains healthy to avoid developing AD or other neurologic conditions:
Avoid harmful substances: Excessive drinking and drug abuse are believed to damage brain cells.
Exercise your brain: Read frequently and do crossword puzzles or other games that challenge your brain. Learn new skills to keep mentally active. Doing so can strengthen the brain's connections and promote the growth of new ones.
Stay socially active: We benefit from interactions with family, friends, and our community.
Exercise your body: Even low-to moderate-level activity such as walking or gardening 3 to 5 times per week can make you feel better and has been shown to help the brain stay active and alert.
Caregiver Health
AD affects both patients and their caregivers. To be able to take the best care of a person with AD, the primary caregiver must take care of themselves, too. They should take time to pursue the things that they find interesting and make them happy. Of most importance, they should not be afraid to ask the doctor questions or to ask others for help!
For More Information
Brain & Life
Alzheimer's Association
BrightFocus Foundation
Alzheimer's Foundation of America
Footnotes
References
- 1.Alcolea D, Schnaider Beeri M, Rojas J, et al. Blood biomarkers in neurodegenerative diseases: implications for the clinical neurologist. Neurology. 2023;101(4):172-180. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 2.Alzheimer's Association. Accessed May 16, 2023. alz.org/