Dementia with Lewy bodies (DLB) is one of the leading causes of dementia, yet clear biomarkers for its diagnosis and monitoring are still lacking. The Lewy bodies in the brains of people with DLB are primarily composed of accumulations of the protein α-synuclein, which can cause synaptic dysfunction from the early stages of the disease. VAMP-2 and SNAP-25 proteins play a key role in synaptic function, facilitating neurotransmitter release. This recently published study in Alzheimer Research and Therapy suggests that the levels of these proteins in cerebrospinal fluid (CSF) could serve as useful tools to detect synaptic dysfunction in DLB.
What was done in this study?
In this study, the levels of VAMP-2 and SNAP-25 proteins in cerebrospinal fluid from DLB patients were evaluated and compared with healthy individuals and Alzheimer’s patients. The goal was to analyze the relationship between these protein levels and Alzheimer’s and neurodegeneration biomarkers, as well as their association with cognitive performance, to determine if they could help differentiate between pure DLB and DLB with Alzheimer’s pathology.
Main Results
- VAMP-2 and SNAP-25 levels were lower in pure DLB compared to controls but higher in DLB with Alzheimer’s pathology, helping to differentiate between these two conditions.
- Both proteins were associated with p-tau and total tau in CSF across all groups and with the Aβ42/40 ratio in Alzheimer’s pathology groups.
- Association with cognitive performance: VAMP-2 and SNAP-25 levels in CSF were associated with phonemic fluency in pure DLB, while SNAP-25 was associated with the clock drawing test and MMSE in DLB and DLB with Alzheimer’s groups.
Relevance of the Study
This study highlights that VAMP-2 and SNAP-25 levels in cerebrospinal fluid could be key biomarkers for detecting synaptic degeneration in DLB. Furthermore, it opens the door to future research to better understand how the processes causing synapse degeneration are interrelated in both DLB and Alzheimer’s disease.