UCLA researchers have provided the first evidence that a simple blood test could be developed to confirm the presence of beta amyloid proteins in the brain, which is a hallmark of Alzheimer’s disease.
Although approximately 5 million Americans are living with Alzheimer’s, no reliable blood-based test currently exists for the neurodegenerative disorder that is the sixth-leading cause of death in the United States. Using blood-based biomarkers - a signature of proteins in the blood that indicate the presence of a disease - to diagnose Alzheimer’s could be a key advance.
“Blood-based biomarkers would have the important advantage of being safe, affordable and easy to administer in large groups or in rural areas, and therefore could have an enormous impact on clinical care and clinical trials alike,” said Dr. Liana G. Apostolova, director of the neuroimaging laboratory at the Mary S. Easton Center for Alzheimer’s Disease Research at UCLA and head of the research team. Results of the study appeared in the journal Neurology.
Alzheimer’s disease can be diagnosed definitively only by examining brain tissue after death. While people are alive, physicians must rely on proxy measures, or biomarkers, along with cognitive symptoms such as memory loss.
Two current methods for determining the beta-amyloid formation characteristic of Alzheimer’s disease both have drawbacks. Cerebrospinal fluid can be obtained from patients, but that requires a spinal tap, an invasive procedure that carries the risk of nerve damage and other serious side effects. Another method, the amyloid PET scan, while effective, exposes subjects to radiation. The PET scan is also expensive and is not typically covered by insurance as a diagnostic test. Also, few medical centers have the technology.
For their study, the UCLA researchers developed a simple signature for predicting the presence of brain amyloidosis - the build-up of amyloid in the brain - including several blood proteins known to be associated with Alzheimer’s disease, along with information routinely obtained in the course of a clinical work-up for patients suspected to have the disease, such as results of memory testing and structural magnetic resonance imaging.
What is Alzheimer’s disease?
Alzheimer’s disease is the most common form of dementia, a serious brain disorder that impacts daily living through memory loss and cognitive changes. Although not all memory loss indicates Alzheimer’s disease, one in ten people over 65 years of age, and over half of those over 85 have Alzheimer’s disease. Currently, 26 million people worldwide have this dementia, and over 15 million Americans will be affected by the year 2050.
Symptoms of Alzheimer’s disease usually develop slowly and gradually worsen over time, progressing from mild forgetfulness to widespread brain impairment. Chemical and structural changes in the brain slowly destroy the ability to create, remember, learn, reason, and relate to others. As critical cells die, drastic personality loss occurs and body systems fail.
Using blood samples and other data from patients with mild cognitive impairment from the Alzheimer’s Disease Neuroimaging Initiative - a large public-private partnership that began in 2004 - the UCLA researchers found that their method could be used to predict the presence of amyloid in the brain with modest accuracy.
“Our study suggests that blood protein panels can be used to establish the presence of Alzheimer’s-type pathology of the brain in a safe and minimally invasive manner,” Apostolova said. “We need to further refine and improve on the power of this signature by introducing new disease-related metrics, but this indicates that such a test is feasible and could be on the market before long.”
Although there is no treatment that can halt or reverse the progression of Alzheimer’s disease, a non-invasive, inexpensive and reliable test for diagnosing the disease could spare people with dementia and their families the anxiety associated with uncertainty, direct them to support services earlier, and improve their likelihood of benefiting from current and future advances in treatment.
Memory problems are typically one of the first signs of Alzheimer’s disease. People with Alzheimer’s have trouble doing everyday things like driving a car, cooking a meal, or paying bills. They may ask the same questions over and over, get lost easily, lose things or put them in odd places, and find even simple things confusing. Some people become worried, angry, or violent.
Not all people with memory problems have Alzheimer’s disease. Mild forgetfulness can be a normal part of aging. Some people may notice that it takes longer to learn new things, remember certain words, or find their glasses.
Sometimes memory problems are related to health issues that are treatable. For example, medication side effects, vitamin B12 deficiency, or liver or kidney disorders can lead to memory loss or possibly dementia. Emotional problems, such as stress, anxiety, or depression, can also make a person more forgetful and may be mistaken for dementia.
Such a test would also have a major impact on research. “With the advent of the amyloid PET scan we are learning that as many as 25-30 percent of subjects who enroll in Alzheimer’s disease clinical trials turn out not to have the disease,” said Apostolova. “That makes it difficult to measure the effects of the treatment being tested.”
Other authors of the study include Kristy Hwang, David Avila, Omid Kohannim, David Elashoff and Sophie Sokolow, all of UCLA; Edmond Teng from UCLA and Veterans Affairs Greater Los Angeles Healthcare System; Paul Thompson from the University of Southern California; Clifford Jack from the Mayo Clinic; William Jagust from the UC Berkeley; Leslie Shaw and Dr. John Trojanowski from the University of Pennsylvania School of Medicine; and Dr. Michael Weiner from the University of Pittsburgh and Department of Veterans Affairs Medical Center in San Francisco.
There were multiple funders for the study including the UCLA Easton Consortium for Alzheimer’s Drug Discovery and Biomarker Development, the National Institute of Mental Health (U01 AG024904), and the Alzheimer’s Disease Neuroimaging Initiative. Please see paper for complete list.
University of California - Los Angeles