Currently, the diagnosis of Alzheimer’s disease involves the use of neuroimaging techniques such as MRI and PET scans. These tests can be costly and may have long wait times for appointments, leading to difficulties in access for some patients, even within the United States.

Accessibility is a very important concern.

Diagnosing Alzheimer’s disease currently involves following guidelines established in 2011 by the National Institute on Aging and the Alzheimer’s Association.

The guidelines, which are called the AT(N) Framework, say that the presence of amyloid plaques, tau tangles, and neurodegeneration in the brain must be found either through imaging or by analyzing CSF samples.

Both current approaches have economic and practical limitations, which highlights the need for the development of convenient and reliable biomarkers for Alzheimer’s disease in blood samples. Using blood samples for testing would be less invasive and require fewer resources compared to the current methods.

There has been a significant stride toward increased accessibility thanks to the introduction of inexpensive technologies that can identify symptoms of Alzheimer’s in the blood without sacrificing quality, as senior author Thomas Karikari pointed out.

Karikari added: “The most important utility of blood biomarkers is to make people’s lives better and to improve clinical confidence and risk prediction in Alzheimer’s disease diagnosis.”

The phosphorylated form of tau and plasma amyloid beta are two of the three criteria needed for an Alzheimer’s diagnosis, and both may be detected by current blood testing procedures. However, the main challenge in using the AT(N) Framework to analyze blood samples is the challenge of identifying neurodegenerative indicators that are unique to the brain and aren’t impacted by potentially deceptive contaminants produced elsewhere in the body.

For example, the protein neurofilament light, which shows that nerve cells are damaged, is found in higher amounts in the blood of people with Alzheimer’s, Parkinson’s, and other dementias. This makes it less useful when trying to tell Alzheimer’s from other neurodegenerative diseases. On the other hand, measuring the amount of total tau in the CSF was more helpful than measuring it in the blood.

By using what they knew about the molecular biology and biochemistry of tau proteins in different tissues, like the brain, Karikari and his team, which included scientists from the University of Gothenburg in Sweden, came up with a way to find the biomarker, called “brain-derived tau,” or BD-tau while avoiding “big tau” proteins made by cells outside of the brain that are free-floating.

To do this, scientists created a specialized antibody that attaches to BD-tau specifically, making it simple to find in blood. They tested their assay on over 600 patient samples from five different groups. This included samples from people whose Alzheimer’s diagnosis was confirmed after they died, as well as samples from people whose memory problems pointed to early-stage Alzheimer’s.

The results demonstrated that the novel assay successfully differentiated Alzheimer’s disease from other neurodegenerative illnesses by accurately measuring BD-tau levels in blood samples from AD patients. Analysis of brain autopsies showed a correlation between BD-tau levels and the extent of amyloid plaques and tau tangles in the brain tissue.

Scientists hope that keeping an eye on blood levels of BD-tau could improve the design of clinical trials and make it easier to screen and enroll patients from groups that haven’t been included in research cohorts in the past.

“There is a huge need for diversity in clinical research, not just by skin color but also by socioeconomic background,” adds Karikari. “To develop better drugs, trials need to enroll people from varied backgrounds and not just those who live close to academic medical centers. A blood test is cheaper, safer and easier to administer, and it can improve clinical confidence in diagnosing Alzheimer’s and selecting participants for clinical trial and disease monitoring.”

The results were published today in Brain.

Source: https://doi.org/10.1093/brain/awac407

Image Credit: Getty