Detecting two proteins in the blood could help predict a patient’s risk of developing Alzheimer’s disease. The protein P-tau181 indicates deposits in the brain, while the light neurofilament (NfL) is created when nerve cells die. Even in patients with minor cognitive problems, the blood level of these two proteins can provide information about the possible development of dementia. Should the method prove to be reliable in further studies, it could replace expensive and invasive early tests for Alzheimer’s in the future.
Around 50 million people worldwide live with dementia. The most common form is Alzheimer’s. Proteins are deposited in the brain, which gradually lead to the death of the nerve cells. So far there is no therapy that can cure Alzheimer’s or reverse the brain damage. Detecting it as early as possible could help slow down progress and test appropriate drugs. Previously established early tests, however, require either an examination of the liquor, which is removed from the spinal cord by lumbar puncture, or a complex and expensive brain scan. Costs, effort and risks limit the use of such early tests. Less expensive and invasive early tests would therefore make sense.
Blood markers as meaningful as CSF examinations
Researchers working with Nicholas Cullen from Lund University in Sweden have now developed such an early test. To this end, they used the data from a total of 573 patients and recorded both the level of various proteins in the blood and the results of CSF examinations. After two and four years, the researchers evaluated the patients who had developed Alzheimer’s during this time. On this basis, they developed computer models that use the blood results to predict the risk of Alzheimer’s disease.
Cullen and his colleagues identified two proteins as particularly meaningful biomarkers: the protein P-tau181, which indicates that the plaques typical of Alzheimer’s disease are forming in the brain, and the light neurofilament (NfL), a protein that is already used as a marker for neuronal Damage is known. If these two proteins are measured in the blood, the computer model created by the researchers calculates the risk of Alzheimer’s disease with a precision that was previously only possible on the basis of CSF examinations and brain scans – two significantly more expensive and more uncomfortable procedures for the patient. “Although the meaning of the biomarkers can vary depending on the context and the intended area of application, the biomarkers from blood plasma are very promising because they are easily available and the investigation costs little,” the researchers write.
Online tool predicts Alzheimer’s risk
To illustrate their results, the researchers offer an online tool. If you enter the patient’s age and gender as well as the results of a standardized test of cognitive abilities, the tool shows the probability that the patient will develop Alzheimer’s disease within two or four years. The results are made more precise if one also answers whether P-tau181 and NfL were detected in the blood. According to the researchers, if all the necessary data is entered, the model they have developed is able to correctly identify patients who will develop dementia (sensitivity) in 89 percent of cases. In 88 percent of the cases it is possible to correctly identify patients who will not develop Alzheimer’s disease within the next four years (specificity).
So far, the online tool has only been used for teaching and research purposes. Before it can actually be included in medical diagnostics, further tests on larger patient groups are required. “This study is an important step towards a blood test for Alzheimer’s, but it’s important to note that we haven’t got there yet,” commented Tara Spiers Jones, professor of neurodegeneration at the University of Edinburgh, who was absent from the study was involved.
Early detection for research purposes
Dementia researcher Tom Dening of the University of Nottingham also points out that the crucial question in early diagnosis is whether it is medically or socially beneficial for the patient. After all, there are currently no effective therapies for Alzheimer’s disease available and preventive measures can at best slow down cognitive decline. So far, early detection has been particularly helpful from a scientific point of view: If risk patients can be reliably identified at an early stage, they can be included in studies at an early stage of the disease and thus help to explore future possibilities for therapy and prevention.
“The hope is that one day people will have routine checks for their Alzheimer’s risk and, if necessary, receive treatment immediately, as is the case nowadays, for example, with high cholesterol levels,” says David Curtis of University College London. “As long as such therapies do not yet exist, such tests are only useful for research purposes.”
Source: Nicholas Cullen (Lund University, Malmö) et al., Nature aging, doi: 10.1038 / s43587-020-00003-5