Blood biomarkers can rule out Alzheimer’s disease in people with subjective memory complaints

A new study led by researchers at the Barcelonaβeta Brain Research Center (BBRC), published in the journal EBioMedicine, provides relevant evidence to improve the clinical management of people with subjective cognitive decline (SCD). These are the first results from the Beta-AARC cohort, an ongoing study launched in 2021 that follows people aged between 55 and 80 with this profile. SCD refers to people who perceive a worsening of their memory or other cognitive abilities but do not show impairment on objective neuropsychological tests.

Subjective memory complaints are a common reason for consultation in both specialised neurology and primary care. However, it is often difficult to provide a precise answer to people who report these complaints, as most clinical guidelines do not initially recommend the use of biomarkers in this population.

A pioneering cohort to study Alzheimer’s disease at its earliest stages

The Beta-AARC cohort is a unique scientific resource, as it focuses exclusively on people with SCD, a group that is particularly underrepresented in the scientific literature. These individuals are at a very early stage of the disease, potentially before biological pathology can be detected using conventional methods, making them an ideal population in which to study the earliest mechanisms of Alzheimer’s disease.

For this first study, the research team analysed data from 142 cohort participants. The study assessed an extensive panel of biomarkers, both in cerebrospinal fluid (CSF) and blood plasma, with the aim of detecting the accumulation of amyloid-beta protein, one of the earliest biological markers of Alzheimer’s disease.

A tool to rule out, not to confirm

The results confirm the utility and accuracy of cerebrospinal fluid biomarkers in identifying the presence of amyloid pathology. In plasma, the biomarkers p-tau217, p-tau217/Aβ42 and p-tau181/Aβ42 demonstrated strong discriminatory performance and high negative predictive value; in other words, they are highly effective in ruling out the presence of amyloid pathology. Given that the prevalence of this pathology is low in people with SCD, their ability to confirm the diagnosis (the positive predictive value) is more limited.

“People with subjective memory complaints represent a unique opportunity to study Alzheimer’s disease before symptoms appear, but they are also the group in which there is the greatest diagnostic uncertainty in clinical practice. This first study from the Beta-AARC cohort shows that blood biomarkers, especially p-tau217, can help clinicians rule out Alzheimer’s disease quickly and accessibly, which may help relieve patients’ anxiety and better guide their follow-up,” says Dr Marc Suárez-Calvet, group leader of the Fluid Biomarkers and Translational Neurology Research Group at the BBRC and corresponding author of the study.

The study, led by researchers José Contador, and Federico E. Pozzi (both BBRC collaborators), clinical neurologist and head of the Brain Health Service at IRCCS Policlinico San Donato, also examined biomarkers related to other pathological pathways that are activated even before cognitive decline, such as glial reactivity, neurodegeneration and synaptic dysfunction. Although some changes were observed, they could not be robustly detected with the plasma biomarkers analysed at this stage.

Overall, the results support the potential of blood biomarkers as screening and risk-stratification tools in people with subjective cognitive decline. Their use could help prioritise which individuals require more invasive or specialised diagnostic tests, as well as facilitate the selection of candidates for prevention studies, clinical trials or future disease-modifying therapeutic strategies.

“This study shows that blood biomarkers can help us provide a more accurate first answer to people who come to the clinic with subjective memory complaints. Their main value in this population is that they may help rule out the presence of Alzheimer’s disease pathology. But the results are also clear: when the aim is to confirm the disease, more specific tests, such as cerebrospinal fluid analysis, remain necessary,” explains Dr. Marc Suárez-Calvet.

Reference article: Contador, J., Pozzi, F. E., Sánchez-Benavides, G., Fernández-Arcos, A., Lantero-Rodríguez, J., Montoliu-Gaya, L., Minguillon, C., Fauria, K., González-Escalante, A., Ortiz-Romero, P., Blasco-Forniés, H., de Diego-Osaba, M., Jiménez Moyano, E., Quijano-Rubio, C., Kollmorgen, G., Le Bastard, N., Nadal, A., Vanmechelen, E., Jeromin, A., Torres-Torronteras, J., … β-AARC Study collaborators (2026). Detecting amyloid-β pathology in subjective cognitive decline using plasma and CSF biomarkers. EBioMedicine, 129, 106331. Advance online publication. https://doi.org/10.1016/j.ebiom.2026.106331