New Assay Helps to Identify Elevated Dementia Risk

The approach relies on the detection of pathological alpha-synuclein proteins

Dresden (Germany), February, 27, 2026. Scientists from DZNE, University Hospital Carl Gustav Carus Dresden, and other research institutions have developed a technique that enables the quantitative measurement of pathological alpha-synuclein in cerebrospinal fluid. This protein is implicated in Alzheimer’s, Parkinson’s, and other neurodegenerative diseases. The new analytical approach may facilitate the identification of individuals at elevated risk of dementia. The related findings – based on data from more than 200 adults – have been published in the journal Alzheimer’s & Dementia. The method is still experimental and will now be further optimized.

In various neurodegenerative diseases, a protein called alpha-synuclein undergoes conformational changes and aggregates within the brain. This is a hallmark of Parkinson’s disease and other „synucleinopathies” such as Lewy body dementia. However, abnormal alpha-synuclein can also occur in Alzheimer’s disease. “Established laboratory tests can detect misfolded alpha-synuclein in cerebrospinal fluid, which is the liquid that surrounds the brain and spinal cord. However, these assays essentially only indicate whether the protein is present in a pathological form or not. They do not measure how much of it is there,” explains Prof. Björn Falkenburger, a DZNE scientist at and Deputy Director of the Department of Neurology at Dresden’s University Hospital.

Quantitative measurement

“We have now expanded the existing methodology to quantify the amount of pathological protein,” says Falkenburger. “We expect this will provide more precise information about disease stage and enable us to stratify patients according to severity. This is relevant for the development of new therapies, which ideally should be tailored to a patient’s individual health status.”

The researchers analyzed cerebrospinal fluid samples from more than 200 older women and men. In addition to cognitively healthy individuals, the cohort included people with subjective memory complaints, mild cognitive impairment, Alzheimer’s dementia, and Lewy body dementia. Participants were recruited from multicenter DZNE studies and from a study cohort at Technische Universität Dresden. Over a four-year period, they were typically examined at least twice, allowing for longitudinal data analysis.

Prognostic potential

The results showed that study participants with a high burden of misfolded alpha-synuclein at baseline had an increased risk of developing dementia during the observation period. Three out of four individuals in this group experienced cognitive decline over time. However, dementia also manifested among participants with lower levels of pathological protein. “These findings suggest that quantitative measurement of alpha-synuclein could help identify at least some patients at increased risk of dementia at an early stage. This would be an important step for diagnostics and for the selection of participants for clinical trials,” says Falkenburger. “Presently, I see the main application of our approach in research. However, before it can be used routinely, further studies are needed to validate and refine the methodology.”

 

Original publication
Alpha-synuclein quantitative seed amplification assay predicts conversion to dementia.
Stefan Bräuer et al.
Alzheimer’s & Dementia: the Journal of the Alzheimer’s Association (2026).
DOI: https://doi.org/10.1002/alz.71167