Tacrolimus immunoassay correlates well with mass spectrometry

An updated tacrolimus immunoassay on whole blood samples shows good agreement with an in-house liquid chromography-tandem mass spectrometry assay (MS), a recent study found (J Appl Lab Med 2026; doi.10.1093/jalm/jfaf199).  

Changing from the MS assay to the immunoassay substantially improved turnaround time (TAT) and workflow, the researchers noted.

MS quantifies tacrolimus accurately and with minimal metabolite interference. But it requires expensive analyzers, highly trained staff, and a manual process. In comparison, immunoassays have faster, simpler workflows but have been prone to cross-reaction with metabolites from tacrolimus and other drugs, leading to falsely elevated results.

The researchers compared their in-house MS tacrolimus assay to another tacrolimus immunoassay and performed a comparative analysis. The researchers also evaluated within-individual imprecision and total imprecision after implementing the immunoassay, plus changes and improvement to workflow and TATs.

The updated immunoassay correlated well with the in-house MS method, with a bias of 0.52 ng/mL. With the switch to the newer one, researchers saw a 42%–51% improvement in TATs across the median, 75th, and 90th percentiles, respectively.

After the switch to the immunoassay, the researchers determined that similar TATs could be achieved with three daily batches instead of four. After reviewing a week’s worth of time studies, a batch took an average of 2.3 hours to complete, with most variability based on batch size. Improvement was partly due to using automated analyzers and aligning number and timing of batches with volume and time of sample receipt.

The immunoassay’s limitations include a need for some manual preparation and varied pipetting skills among automated lab staff. Study limitations include the lack of a formal interference study to determine cross-reactivity of metabolites or interferents, the researchers noted.

Circular RNAs predict Alzheimer’s disease risk

Recent research proposed 34 circular RNAs (circ-RNAs) in the blood as potential Alzheimer’s disease (AD) biomarkers whose combined expression patterns accurately distinguished Alzheimer’s disease from healthy aging (Nat Med 2026; doi: 10.1038/s41591-026-04485-5).

Current AD blood tests offer reliable diagnoses by detecting markers of amyloid plaques that can yield positive results potentially decades before cognitive impairment, but provide little information about disease progression. CircRNAs, on the other hand, resist degradation, are plentiful in the brain, and reflect changes occurring there.

To explore circRNAs as markers of patterns associated with future cognitive impairment before symptoms appear, researchers analyzed cross-sectional blood samples from 1,221 people, including healthy individuals and those with AD. They looked for circRNAs associated with AD clinical status, Aβ and Tau stages, and progression to symptomatic AD. To develop and validate predictive models of AD diagnosis and disease progression, the researchers replicated their findings in independent samples from two cohorts.  

After identifying a set of 34 circRNAs that were associated with AD, the researchers developed predictive models based on these associations that successfully identified individuals with AD pathology. These models performed similarly to those trained on data regarding the leading clinical blood-based biomarker for AD, the protein pTau217.

The researchers compared their predictive model, including these 34 circRNAs, amyloid-β, and Tau status, and replicated the model in 51 independent samples. Seventy-six were from AD patients and 475 were from patients without cognitive impairment. They also used the model in 1,767 samples from preclinical AD patients. Classification of biomarker-confirmed status by blood circRNAs had a higher predictive ability with area under the curve (AUC) of 0.945, versus plasma pTau217, with an AUC of 0.877.  

The researchers also found evidence that circRNA changes begin approximately 2–4 years before the onset of clinical symptoms, which suggests that these molecules may capture biological processes closely linked to the transition from silent pathology to cognitive decline.  

The researchers called for prospective validation in larger cohorts.  

apoB testing may be a cost-effective prevention strategy

Apolipoprotein B (apoB) might be used as a cost-effective marker to guide primary prevention lipid-lowering therapy (LLT) and improve population health, a computer simulation study suggests (JAMA 2026; doi:10.1001/jama.2026.2986).

Unlike standard cholesterol tests, apoB measures the number of cholesterol carrying particles that can contribute to plaque buildup. Researchers say that makes it a more direct indicator of cardiovascular risk. Even with growing evidence supporting apoB, the test still is not commonly used in routine care, partially because measuring apoB generally requires an additional blood test beyond the standard cholesterol panel, increasing both cost and inconvenience.

The study examined whether it is worth spending extra money to use apoB instead of low-density lipoprotein cholesterol (LDL-C) or non–high-density lipoprotein cholesterol (non–HDL-C) to guide treatment intensifications as a means of primary prevention.

In a computer simulation and economic evaluation study, the researchers compared cost-effectiveness of using LDL-C, non–HDL-C, and apoB goals in a cohort of 250,000 atherosclerotic cardiovascular disease–free and statin-eligible U.S. adults, constructed from 4,149 National Health and Nutrition Examination Survey participants in the years 2005–2016.  

Individuals started the simulation after lipid screening and received statin therapy based on 2018 American Heart Association and American College of Cardiology guidelines. The researchers intensified lipid-lowering therapy for patients who did not achieve these goals: LDL-C level less than 100 mg/dL, non–HDL-C level less than 118 mg/dL, or apoB level less than 78.7 mg/dL. The primary outcome was the incremental cost-effectiveness ratio. Strategies were considered cost-effective if they cost less than $120,000 per quality-adjusted life year (QALY) gained in 2025 dollars, adjusted for inflation.

Compared with a non–HDL-C goal, 1,324 QALYs would be gained with an apoB goal, alongside a $40.2 million increase in costs, yielding an incremental cost-effectiveness ratio of $30,300 per QALY gained. Compared with an LDL-C goal, 965 QALYs would be gained with a non–HDL-C goal, alongside a $2.1 million reduction in costs, the researchers found.

At a willingness-to-pay threshold of $120,000 per QALY gained, an apoB goal was optimal in 65% of probabilistic analyses, and a non–HDL-C goal was optimal in 25%.  

The cost of apoB testing was marginal. Higher costs reflected longer life expectancy and prolonged preventive treatment, the researchers noted.

Read the full September-October issue of CLN.