Blood Test Accurately Diagnoses Alzheimer’s, Reducing False Positives

A new blood test developed in Sweden offers a more precise way to diagnose Alzheimer’s disease in patients experiencing cognitive decline, significantly reducing false positive diagnoses. The test, spearheaded by Niklas Mattsson-Carlgren and his team at Lund University, distinguishes between advanced stages of the disease and earlier, preclinical signs, according to research published in The Lancet Neurology.

The breakthrough centers on combining measurements of two biomarkers in blood: p-tau217 and eMTBR-tau243. This combination reduced false positive diagnoses from 43% to 16%, according to data presented by Mattsson-Carlgren, who is a senior lecturer, consultant, and specialist in clinical memory research at Lund University and Skåne University Hospital.

Previous blood tests for Alzheimer’s have been able to detect brain changes up to two decades before symptoms appear, but struggled to pinpoint the disease stage or differentiate it from other disorders. The Lund University team’s approach addresses this limitation. By utilizing both biomarkers, researchers were able to identify individuals with established Alzheimer’s disease with approximately 80% accuracy. Of 350 patients with elevated p-tau217 levels, 199 already met the diagnostic criteria for the disease.

Though, the addition of the eMTBR-tau243 marker refined the diagnosis further. 194 cases (55% of those positive for p-tau217) also tested positive for eMTBR-tau243, substantially decreasing the number of false positives.

The p-tau217 biomarker is a modified form of the tau protein, which appears in the brain as Alzheimer’s progresses. Normally, tau protein helps stabilize nerve cells, but chemical alterations cause it to form neurofibrillary tangles, a process detectable in blood samples. Researchers found that 97% of the 350 individuals with high levels of p-tau217 also exhibited amyloid in their brains – a hallmark of Alzheimer’s pathology.

Mattsson-Carlgren explained that current tests can sometimes return positive results in individuals who do not yet meet all the clinical criteria for the disease, leading to false positives. “In some cases, a blood marker can be positive in people who do not yet meet the criteria for the disease; these are known as false positives,” he stated. The combined apply of eMTBR-tau243 reduced this rate to 16%, increasing clinical reliability.

Longitudinal patient data revealed that those with both biomarkers present in their blood experienced a more rapid cognitive decline and increased tau accumulation in the brain, offering both diagnostic and prognostic value. The study involved 572 individuals presenting with cognitive impairment and participating in the BioFinder2 project, with results validated against a separate cohort of American patients with similar symptoms.

“By combining blood markers, People can better identify who has Alzheimer’s disease and who is at a stage of the disease where symptoms are present,” Mattsson-Carlgren said. This advancement improves upon the challenges of distinguishing Alzheimer’s from other forms of dementia in early stages and aids in determining when to initiate specific treatments or enroll patients in clinical trials.

Currently, the new marker requires sophisticated analysis techniques, such as mass spectrometry, limiting its widespread use outside specialized centers. Mattsson-Carlgren indicated that future research will focus on simplifying the test and evaluating its potential for use in primary care settings, which would broaden access to early and accurate diagnosis.

Alzheimer’s disease is the most common cause of dementia, accounting for 60-70% of cases worldwide, according to the World Health Organization. Accurate identification of the disease stage and subtype is crucial not only for treatment but also for planning and delivering appropriate social and healthcare resources to patients and their families.