A blood test helps predict the risk of Alzheimer's disease, many years before symptoms such as memory problems occur, according to research by US scientists. An article on this topic is published in the journal “Nature Medicine”.
According to the authors of the study, the use of this test would allow for earlier implementation of preventive measures, delaying the development of memory disorders and other cognitive functions in Alzheimer's patients. It may also help better plan clinical trials of new drugs.
Alzheimer's disease is the most common cause of dementia. It is characterized by the presence of pathological structures in the brain of patients: extracellular deposits of the so-called amyloid plaques, consisting mainly of amyloid-beta 42, and intracellular deposits called neurofibrillary tangles, composed mainly of the phosphorylated form of tau protein.
As the authors of the latest study recalled, the amount of amyloid plaques, assessed using positron emission tomography (PET), increases for approximately 10–20 years in the preclinical phase of Alzheimer's disease, in which patients do not have cognitive impairment. It then stabilizes when symptoms of the disease appear. In turn, neurofibrillary tangles – as shown by PET studies – develop later, and their number increases with the severity of the symptoms of the disease.
Race against time – why is the preclinical phase crucial?
Recently, drugs have appeared that can slow down the development of Alzheimer's, provided that they are used in the early symptomatic phase of the disease. However, specialists estimate that better effects could be achieved if these therapies were used in the earlier, preclinical phase of Alzheimer's, before major neurodegenerative changes occur in the brain.
However, the use of brain imaging techniques (such as PET) to identify people who are in the preclinical phase of the disease and who may develop symptoms in a few years is expensive and burdensome, especially since these methods have limited availability. Therefore, scientists are striving to develop simpler and more economical blood tests.
Researchers from Washington University School of Medicine in St. Louis (USA) focused on measuring the concentration of tau protein phosphorylated at position 217 (p-tau217) in plasma, and specifically on the change in the concentration of p-tau217 in relation to the concentration of tau protein that was not phosphorylated at this position.
Previous studies have shown that plasma levels of p-tau217 closely mirror the accumulation of both tau and amyloid in the brain, as confirmed by PET scans.
To check whether an increase in the plasma level of p-tau217 compared to its unphosphorylated form can be an indicator used to predict the occurrence of Alzheimer's symptoms, scientists conducted research among 603 participants of two long-term studies on this disease – Knight ADRC and ADNI. In both groups, changes in p-tau217 levels were measured using different tests.
It turned out that based on changes in the level of p-tau217 in relation to the unphosphorylated form of this protein, it was possible to estimate the age at which the symptoms of Alzheimer's disease would appear with a margin of error of about three to four years.
How quickly these symptoms may appear after an increase in plasma p-tau217 levels is noted depends on the patient's age. For example, in people whose p-tau217 levels increased at the age of 60, the median time to onset of symptoms was 20.5 years, and in people whose p-tau217 levels increased at the age of 80, the median was only 11.4 years.
Patient's age and the rate of disease progression
According to the researchers, this pattern suggests that the brains of younger people may tolerate disease-related changes longer, while in older people symptoms may appear at lower levels of pathological changes.
– Our work shows that it is possible to predict the occurrence of Alzheimer's disease symptoms thanks to blood tests, which are much cheaper and more accessible than brain scans or cerebrospinal fluid tests – commented co-author of the work, Dr. Suzanne E. Schindler.
According to the scientists, the results of their analyzes may help design more targeted clinical trials of therapies aimed at preventing Alzheimer's disease or slowing its progression. Over time, this may also help identify those most likely to benefit from early therapeutic intervention.
Study co-author Dr. Kellen K. Petersen explained that the levels of tau and amyloid proteins can be compared to the rings of a tree trunk, based on which its age can be assessed. By taking into account the level of p-tau217 protein, which reflects the accumulation of both amyloid and tau protein in the brain, it can be possible to predict how long it will take for someone to develop symptoms of Alzheimer's disease.
Researchers emphasize that the p-tau217 test can now help doctors diagnose Alzheimer's disease in patients with cognitive impairment. However, these tests are not recommended for asymptomatic people, except in research or clinical trials.
Dr. Petersen added that other biomarkers present in the blood may also reflect the risk of cognitive decline in Alzheimer's disease. Taking them into account in future studies may further improve methods of predicting the time of onset of symptoms of this disease.
“If further refined, these methodologies have the potential to predict symptom onset accurately enough that we could use them in individual clinical care,” the researcher concluded. (PAP)
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