The term “blood marker” refers to any substance found in the blood that can indicate the presence or activity of a particular disease. Blood markers are a powerful diagnostic tool, often used to diagnose and monitor conditions like cancer. Researchers have long sought effective blood markers for neurodegenerative conditions like Alzheimer’s disease (AD), which affects millions worldwide. Not only would an effective AD blood marker increase the chances of early diagnosis, which could potentially improve patient outcomes when paired with prompt treatment, but it could also spare patients from more invasive diagnostic procedures. AD researchers have flagged two blood phosphorylated tau (phospho-tau) species as promising AD blood marker candidates: p-tau181 and p-tau217. However, these phospho-tau species aren’t just elevated in the blood of AD patients; they’re also elevated in the blood of individuals with amyotrophic lateral sclerosis (ALS), another neurodegenerative condition.
A new study explored the two phospho-tau species as potential diagnostic tools for AD, ALS, or both. The findings have complex, but potentially promising implications for neurological research.
Evaluating Blood Phospho-Tau in AD and ALS
As phospho-tau species, both p-tau181 and 217 are considered early markers of tau pathology, or the abnormal accumulation of the tau protein in neurons. This pathology is frequently observed in individuals with AD. However, as mentioned above, the markers are also observed in the blood of individuals with ALS. Recent AD research has focused on p-tau217, which is generally considered a more specific marker for AD when compared with p-tau181. P-tau181, on the other hand, has been more closely associated with ALS.
The research team behind the study, published in March 2025, wanted to answer an intriguing question: Could p-tau217 and 181 serve as effective diagnostic markers for AD or ALS, even though the markers aren’t exclusive to one condition or the other?
Could Phospho-tau Be a Reliable Diagnostic?
To evaluate p-tau181 as a blood marker for both AD and ALS, the researchers began by testing the blood and cerebrospinal fluid (CSF) of individuals at several health care centers in Europe. Of the 362 volunteers, 152 had ALS, 111 had AD, and 99 were controls who did not have neurodegenerative or muscular diseases.
As expected, the team observed high levels of serum p-tau181 in both individuals with AD and individuals with ALS. Serum p-tau217 was also found to be elevated in both types of patients, although it was higher in patients with AD. Ultimately, the scientists were able to distinguish between AD and ALS based on serum p-tau217 levels with moderate accuracy. Ultimately, though, p-tau217 may not offer enough of a distinction between the two diseases to be a reliable diagnostic.
Clinical Implications for AD and ALS Patients
While these blood markers may not be as distinct as researchers hoped, the study revealed several other interesting biomarker clues. For example, the team compared the muscle fibers of people with ALS, evaluating muscle fibers that showed signs of atrophy against muscle fibers that still appeared healthy. They found that there were far more p-tau isoforms in the atrophying muscle fibers. This could help researchers determine how p-tau181 and 217 are released into the blood in ALS patients.
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Have scientists confirmed phospho-tau as a blood biomarker for AD or ALS? Not quite. However, there is hope that these markers could serve as general population screening tools for AD, particularly for early screening to identify at-risk individuals. With early detection and treatment, patient outcomes could be vastly improved.
To study p-tau in AD and ALS, Scantox Neuro offers several preclinical in vitro and in vivo models. Levels of p-tau and its different isoforms can be evaluated using biochemical and histological methods. Furthermore, other biomarkers of neurodegeneration, such as neurofilament light chain levels, can be assessed.
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