Can a Single Blood Sample Close the Alzheimer’s Screening Gap for People With Down Syndrome?

People with Down syndrome face an extremely high risk of Alzheimer’s disease, yet they have long been excluded from the validation of many diagnostic technologies. An exploratory study led by the University of Southern California found that two blood tests already used in general Alzheimer’s research or clinical assessment may also identify amyloid pathology in the brains of people in this population from their blood, opening the door to more accessible initial screening.

The study included 39 adults without dementia from the U.S. National Institutes of Health’s Trial-Ready Cohort for Down Syndrome. Plasma phosphorylated tau 217 (p-tau217) was measured using the Lumipulse and PrecivityAD2 platforms and compared with amyloid positron emission tomography results. The researchers defined PET values above 18 centiloids as positive; the areas under the curve for identifying positive cases were 0.94 and 0.91, respectively.

Using cutoffs derived from these samples, Lumipulse and PrecivityAD2 achieved overall accuracies of 90% and 92%, respectively, with both reaching a negative predictive value of 97%. This indicates that the tests rarely missed PET-positive participants in the study. In the future, blood testing could potentially be used first to rule out cases with a low likelihood of amyloid pathology, followed by PET or cerebrospinal fluid testing to confirm positive results, reducing the burden of invasive procedures, radiation exposure, and travel to major medical centers.

### Background

Down syndrome is caused by an extra copy of chromosome 21, which also contains the APP gene encoding amyloid precursor protein. People with Down syndrome often begin accumulating amyloid in the brain at an earlier age, but the presence of plaques does not mean that dementia has already developed; conditions such as depression and sleep apnea can also cause cognitive or behavioral changes. The ability to reliably rule out Alzheimer’s therefore affects not only diagnosis, but also whether physicians should look for other treatable causes.

The findings could also change how participants are recruited for research. Participants came from an observational cohort that continuously collects cognitive assessments, imaging, biomarkers, and specimens, with one of its aims being to establish a population that can be rapidly enrolled in Alzheimer’s prevention trials. If blood tests can first identify people likely to have amyloid pathology, research teams could reduce their reliance on costly imaging during large-scale recruitment and give adults with Down syndrome, who have historically been less frequently included in trials, more opportunities to participate.

However, a sample of 39 people is insufficient to establish a clinical standard, and the optimal cutoffs used in the study were derived from the same dataset, potentially overestimating real-world performance. All participants were free of dementia, so the results also cannot directly determine whether the tests can diagnose symptomatic disease. The study authors also disclosed relevant financial relationships with testing companies and Alzheimer’s drug manufacturers. The thresholds must next be validated in larger, more diverse populations of people with Down syndrome spanning different disease stages. Until then, these figures should be viewed as a strong preliminary signal, not as a basis for independently determining diagnosis or treatment.