LITERATURE UPDATE The diagnostic performance of the
Lumipulse G plasma p-tau217/Aβ42 ratio was evaluated using Aβ and tau positron emission tomography (PET) as reference standards in a clinic cohort (n=391) and a community cohort (n=121).
Plasma p-tau217/Aβ42 exhibited
high performance for abnormal statuses of Aβ PET (area under the curve [AUC]: 0.963 to 0.966) and tau PET (AUC: 0.947 to 0.974), which were clinically equivalent to those of cerebrospinal fluid (CSF) p-tau181/Aβ42 and Aβ42/Aβ40 and higher than those of blood p-tau217, Aβ42/Aβ40, p-tau181, and p-tau181/ Aβ42 in both clinic and community cohorts. Applying a two-cut-off approach improved the specificity without reducing sensitivity. The p-tau217/Aβ42 ratio had a lower intermediate percentage than p-tau217 alone in both clinic (10.6% vs. 13.0%) and community (16.5% vs. 31.4%) cohorts.
Plasma p-tau217/Aβ42 has high
performance in detecting cerebral AD pathologies, thus offering a promising tool for clinical diagnosis and community screening of AD. Lumipulse G plasma p-tau217 and
the p-tau217/Aβ42 ratio accurately identified abnormal Aβ and tau PET statuses in both clinical and community cohorts. The performance of plasma p-tau217 and p-tau217/Aβ42 ratio were equivalent to CSF tests. Plasma p-tau217/ Aβ42 ratio outperformed p-tau217 alone in identifying Aβ PET positivity, and this superiority is more obvious in the community cohort, suggesting an advantage in the early diagnosis of AD. Two cut points of p-tau217/Aβ42 were established in the Chinese population for clinical laboratory and community screening uses.
The pTau217/Aβ1-42 plasma ratio: The first
FDA-cleared blood biomarker test for diagnosis of Alzheimer’s disease Hu S, Yu H, Gao J. Drug Discov Ther. 2025 Jul 4; 19 (3): 208–209. doi: 10.5582/ddt.2025.01055.
As the most prevalent form of dementia, Alzheimer’s disease (AD) represents a major public health challenge. Early diagnosis is crucial to delaying disease progression, and yet the gold standard for detection of biomarkers – cerebral positron emission tomography (PET) imaging and cerebrospinal fluid (CSF) biomarker analysis – is constrained by invasiveness, high costs, and limited accessibility. On 16 May 2025, the FDA granted
its first clearance to the Lumipulse G blood test, which utilises the plasma
pTau217/Aβ1-42 ratio, for the diagnosis of
amyloid plaques in symptomatic patients age 55 or older. In clinical validation, concordance rates with amyloid PET brain scans/the results of CSF biomarker detection were 91.7% (positive) and 97.3% (negative).
Similar blood-based assays have
previously been approved in Japan (HISCL Aβ42/40
), the United Kingdom
(PrecivityAD2), and China. While concerns regarding false-positive/false- negative rates necessitate continued attention and their role as adjunctive diagnostic tools requires integration with comprehensive clinical assessment and other tests, the rapid development and regulatory clearance of these blood- based biomarker assays undeniably offer promising prospects for transforming the diagnostic and therapeutic paradigm for AD.
Plasma phospho-tau217 for Alzheimer’s disease diagnosis in primary and secondary care using a fully automated platform Palmqvist S, Warmenhoven N, Anastasi F et al. Nat Med. 2025 Jun; 31 (6) :2036–2043. doi: 10.1038/s41591-025-03622-w.
Global implementation of blood tests for Alzheimer’s disease (AD) would be facilitated by easily scalable, cost- effective and accurate tests. In the present study, the authors evaluated plasma phospho-tau217 (p-tau217) using predefined biomarker cut-offs. The study included 1,767 participants with cognitive symptoms from four independent secondary care cohorts in Malmö (Sweden, n=337), Gothenburg (Sweden, n=165), Barcelona (Spain, n=487) and Brescia (Italy, n=230), and a primary care cohort in Sweden (n=548). Plasma p-tau217 was primarily measured using the fully automated, commercially available, Lumipulse immunoassay. The primary outcome was AD pathology defined as abnormal cerebrospinal fluid (CSF) Aβ42:p-tau181. Plasma p-tau217 detected AD pathology with areas under the receiver operating characteristic curves of 0.93–0.96. In secondary care, the accuracies were 89–91%, the positive predictive values 89–95% and the negative predictive values 77–90%. In primary care, the accuracy was 85%, the positive predictive values 82% and the negative predictive values 88%. Accuracy was lower in participants
aged ≥80 years (83%), but was unaffected by chronic kidney disease, diabetes, sex, APOE genotype or cognitive stage. Using a two-cut-off approach, accuracies increased to 92–94% in secondary and
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primary care, excluding 12–17% with intermediate results. Using the plasma p-tau217:Aβ42 ratio did not improve accuracy but reduced intermediate test results (≤10%). Compared with a high-performing
mass spectrometry-based assay for percentage p-tau217, accuracies were comparable in secondary care. However, percentage p-tau217 had higher accuracy in primary care and was unaffected by age.
In conclusion, this fully automated
p-tau217 test demonstrates high accuracy for identifying AD pathology. A two- cut-off approach might be necessary to optimise performance across diverse setings and subpopulations.
Predicting onset of symptomatic Alzheimer’s disease with plasma p-tau217 clocks Petersen KK, Milà-Alomà M, Li Y et al.; Alzheimer’s Disease Neuroimaging Initiative (ADNI); Foundation for the National Institutes of Health (FNIH) Biomarkers Consortium Plasma Aβ and Phosphorylated Tau as Predictors of Amyloid and Tau Positivity in Alzheimer’s Disease Project Team. Nat Med. 2026 Mar; 32 (3): 1085–1094. doi: 10.1038/s41591-026-04206-y.
Predicting not just if, but also when, cognitively unimpaired individuals are likely to develop onset of Alzheimer’s disease (AD) symptoms would be useful to clinical trials and, eventually, clinical practice. Although clock models based on amyloid and tau positron emission tomography (PET) have shown promise in predicting the onset of AD symptoms, a model based on plasma biomarkers would be more accessible. Using longitudinal plasma %p-tau217
(the ratio of phosphorylated to non- phosphorylated tau at position 217) from two independent cohorts (n=258 and n=345), clock models were used to estimate the age at plasma %p-tau217 positivity. The estimated age at plasma %p-tau217 positivity was associated with the age at onset of AD symptoms (adjusted R2
of 0.337–0.612)
with a median absolute error of 3.0–3.7 years. Notably, the time from %p-tau217 positivity to onset of AD symptoms was markedly shorter in older individuals. Similar models were constructed with data from one p-tau217/Aβ42 immunoassay and four plasma p-tau217 immunoassays. These findings suggest that the time
until onset of AD symptoms can be estimated using a single blood test within a margin of error that is acceptable for use in clinical trials.
PPi
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