Researchers from Missouri reveal that blood test screening may identify markers of Alzheimer's disease before individuals begin to experience memory loss and confusion. This finding is a significant step toward predicting disease risk.
The research was presented at the Alzheimer's Association International Conference, held in London, United Kingdom, and the findings were published in the journal Alzheimer's and Dementia.
For people with Alzheimer's disease, extensive neuronal loss occurs before symptoms of the disease begin to appear. As the brain engages in daily tasks, it repeatedly produces and clears away a sticky protein called amyloid beta. Some of the amyloid beta gets washed away in the blood and cerebrospinal fluid.
But if the protein begins to build up, it can accumulate into plaques in the brain, stick to neurons, and cause neurological damage, contributing to the development and progression of Alzheimer's disease.
For this reason, there is an urgent need for simple screening tests that can predict a person's risk for Alzheimer's disease long before plaque buildup occurs. At present, the only methods that are viable for detecting amyloid beta in the brain are using positron emission tomography (PET) scanning or a spinal tap.
However, PET scanning is expensive and "not widely available," and a spinal tap is invasive and requires a "specialized medical procedure" provided by very few practitioners.
Assessing blood test feasibility
To overcome these hurdles, researchers assessed measures of amyloid beta present in blood to find out whether a blood test could help to identify altered levels of the protein in an individual's brain and cerebrospinal fluid.
Blood screening implementation could be a cheap and less invasive way of selecting those people more likely to develop Alzheimer's disease, years before they would receive a diagnosis based on their symptoms. However, previous studies have not demonstrated a correlation between measures of amyloid beta in the blood and brain.
Senior study author Dr. Randall J. Bateman, the Charles F. and Joanne Knight Distinguished Professor of Neurology at the Washington University School of Medicine in St. Louis, MO, and team conducted a study involving 41 individuals aged 60 and older to assess blood concentrations of amyloid beta.
A total of 23 people were amyloid positive, which means that they had signs of cognitive impairment. These participants had PET scans or spinal taps to confirm the presence of amyloid plaques in the brain or amyloid alterations in their cerebrospinal fluid.
The remaining 18 participants involved in the study, none of whom had amyloid buildup, were also measured for subtypes of the protein.
The levels, production, and buildup of amyloid were measured by taking 20 blood samples from each individual over the course of 24 hours.
'Single sample' located amyloid plaques
The researchers discovered that in people with amyloid plaques, levels of amyloid beta 42 relative to amyloid beta 40 were consistently around 10 to 15 percent lower.
"Amyloid plaques are composed primarily of amyloid beta 42, so this probably means that it is being deposited in the brain before moving into the bloodstream," explains Dr. Bateman.
"The differences are not big, but they are highly consistent. Our method is very sensitive, and particularly when you have many repeated samples as in this study - more than 500 samples overall - we can be highly confident that the difference is real. Even a single sample can distinguish who has amyloid plaques."
Dr. Bateman and colleagues found that they could accurately classify people as either amyloid-positive or amyloid-negative by averaging the ratio of amyloid beta 42 to amyloid beta 40 over each of the participant's 20 blood samples.
By using the average of 20 samples, the team were able to correctly classify people 89 percent of the time, and, based on one sample, they were 86 percent accurate.
"Our results demonstrate that this amyloid beta blood test can detect if amyloid has begun accumulating in the brain. This is exciting because it could be the basis for a rapid and inexpensive blood screening test to identify people at high risk of developing Alzheimer's disease."
Dr. Randall J. Bateman
In addition to amyloid plaques, tangles of a brain protein called tau is a sign of Alzheimer's disease. Dr. David Holtzman, head of the Department of Neurology at the Washington University School of Medicine, is currently working on a blood test for tau. Blood screening for tau could complement the amyloid blood test for added accuracy.
"If we had a blood test for tau as well, we could combine them to get an even better idea of who is most at risk of developing Alzheimer's disease. That would be a huge step forward in our ability to predict, and maybe even prevent, Alzheimer's disease," Dr. Bateman concludes.