New blood biomarkers enable differentiation between the main neurodegenerative diseases that cause dementia

An international team has identified new blood biomarkers that could help distinguish between the main neurodegenerative diseases that cause dementia. The research, published in Nature Aging, analyses more than one thousand plasma proteins and develops a quantitative panel of 21 biomarkers to differentiate between Alzheimer’s disease, dementia with Lewy bodies and frontotemporal dementia.

The study was co-led by Dr Marta del Campo, Director of the Fluid Biomarkers Facility at the Barcelonaβeta Brain Research Center (BBRC), and senior and corresponding author of the study. Her contribution, together with that of Dr Giovanni Belomo from Link Campus University in Rome and Dr Charlotte Teunissen from Amsterdam UMC, focused on the development and validation of the biomarker panel.

In recent years, significant progress has been made in developing blood biomarkers to detect the amyloid and tau alterations characteristic of Alzheimer’s disease. However, few tools are currently available to distinguish Alzheimer’s from other causes of dementia, which may present with similar symptoms, particularly in the early stages.

“Alzheimer’s is not the only cause of dementia. There are also diseases such as dementia with Lewy bodies and frontotemporal dementia, for which we still do not have sufficiently specific blood biomarkers,” explains Dr del Campo. “In this study, we analysed the main forms of dementia together to understand which changes are specific to, or shared between, the different causes of cognitive decline and to identify biomarkers capable of distinguishing between them.”

A single panel for different types of dementia

The research was carried out as part of the international bPRIDE project — blood Proteins for early Discrimination of dEmentias — which aimed to discover and validate blood proteins capable of differentiating between types of dementia at an early stage. The project brought together samples and data from international cohorts and enabled the analysis of more than 1,000 proteins in people with Alzheimer’s disease, dementia with Lewy bodies and frontotemporal dementia. The findings provided the basis for selecting and validating the biomarker panel presented in this study.

In the first phase, the team analysed 1,318 plasma samples from six international cohorts and identified more than 200 proteins whose levels were altered in at least one of the diseases studied. Based on these results, the researchers selected 21 proteins and incorporated them into a single multiplex panel. This technology allows all the selected biomarkers to be measured simultaneously and quantitatively in a single blood sample.

The panel was subsequently validated in an independent multicentre cohort. The results showed that the identified protein combinations could distinguish dementia with Lewy bodies and frontotemporal dementia both from people without dementia and from people with Alzheimer’s disease.

“One of the most relevant aspects of this work is that we have not developed a separate test for each disease, but rather a single assay that integrates the biomarkers of interest,” says Dr del Campo. “The aim is to move towards an accessible and reproducible tool that can help guide the differential diagnosis of dementia.”

Biomarkers for diseases associated with alpha-synuclein

One of the study’s most notable findings relates to dementia with Lewy bodies, a disease characterised by the abnormal accumulation of alpha-synuclein in the brain. This protein also plays a central role in Parkinson’s disease.

The researchers also assessed these findings in an independent cohort of people with Parkinson’s disease. The alterations observed were similar, strengthening the potential association between these biomarkers and diseases linked to alpha-synuclein accumulation.

“These results are particularly relevant because we currently have no blood biomarkers for dementia with Lewy bodies or Parkinson’s disease,” explains Dr del Campo. “The identified candidates will require further validation, but they open up a promising avenue for detecting these conditions through a blood sample.”

Towards a more precise and accessible diagnosis

Correctly distinguishing between the different causes of dementia is essential, as each disease involves different biological mechanisms and may require specific treatments and monitoring strategies. A more precise diagnosis could also facilitate the selection of participants for clinical trials and improve the evaluation of new treatments.

The panel is still at the research stage and will need to be validated in larger and more diverse cohorts before it can be introduced into clinical practice. The next steps will include assessing its usefulness in the earliest stages of disease and optimising its ability to differentiate between diagnoses.

This line of research is aligned with the work of the BBRC’s Fluid Biomarkers Platform, led by Dr del Campo, which focuses on developing and validating accessible and minimally invasive blood tests to improve the detection and differential diagnosis of Alzheimer’s disease and other neurodegenerative diseases.

Reference article: Bellomo, G., Vermunt, L., in ’t Veld, S. et al. “Plasma proteome profiling identified biomarkers for the differential diagnosis and molecular staging of neurodegenerative dementias”. Nature Aging (2026). DOI: 10.1038/s43587-026-01162-7.