An observational study of 26 patients with suspected sepsis, conducted in the United Kingdom, has found that the Alzheimer’s disease biomarker, phosphorylated-tau-217 (p-tau-217), was elevated in people presenting with suspected infection compared to non-infected age and sex matched control subjects. In this study, blood samples from people with suspected sepsis (the body’s extreme, life-threatening response to an infection) and no history of dementia, were collected within 12 hours of their presentation to emergency departments in England and Scotland, and analysed for a range of markers of inflammation and biomarkers of disease pathology. Samples were also collected from 20 non-infected volunteer participants who were enrolled in the National Institute of Health and Care Research BioResource, and nine Alzheimer’s disease ‘positive’ controls.
The authors then used correlation analysis, a statistical method used to determine if a relationship exists between two or more variables (in this case suspected sepsis and p-tau-217 levels), and how strong that relationship is. Lastly, they categorized p-tau-217 levels across all of the samples, according to established thresholds or cut-points used to rule in/out an Alzheimer’s disease diagnosis in clinical practice (low <0.4 pg/ml, intermediate 0.4–0.63 pg/ml, and high >0.63 pg/ml). The authors reported that there was a significant difference in p-tau-217 levels between patients with suspected sepsis and healthy controls, but not between patients with suspected sepsis and Alzheimer disease positive controls. This relationship remained even when the authors controlled for certain confounding factors (characteristics that might play a role in the results) and when they removed participants from the analysis who might have another reason for elevated p-tau-217 (past history of stroke). Across all non-infected controls with p-tau-217 results, 90% had levels of p-tau-217 classified as low levels, 67% of Alzheimer’s disease controls had levels classed as high (>0.63 pg/ml) and 46% of suspected infection patients with no prior history of dementia had a p-tau-217 level classified as high (29%) or intermediate (17%).
The authors caution that these findings are exploratory and must be confirmed in larger samples, however they conclude they are nevertheless important given the current context of p-tau-217 research and its future clinical application as a diagnostic biomarker. They highlight that the findings might: 1) add weight to the infection hypothesis of neurodegenerative diseases; 2) contribute to our understanding of variability in p-tau-217 levels and the implications this has for the timing of testing, frequency of testing and interpretation of results.
More information on this study is available here: https://pubmed.ncbi.nlm.nih.gov/41822110/
