Abstract
Alzheimers Dement. 2025 Dec;21 Suppl 7:e108554. doi: 10.1002/alz70861_108554.
ABSTRACT
BACKGROUND: Given the clinical and pathological heterogeneity of frontotemporal dementia (FTD), there remains a critical need for tools that support the development and implementation of sensitive and specific fluid biomarkers. Emerging technologies, such as NULISA (Nucleic Acid Linked Immunosorbent Assay), offer the potential for improved detection capabilities. In this study, we evaluated the NULISA CNS panel in plasma samples from participants in the Genetic FTD Initiative (GENFI) cohort to explore its utility in the context of FTD.
METHOD: We used the CNS NULISA panel containing 124 targets in plasma samples from the GENFI cohort. We measured a total of 743 participants including 238 C9orf72 expansion carriers (151 presymptomatic and 87 symptomatic), 166 GRN mutation carriers (113 presymptomatic and 53 symptomatic), 100 MAPT mutation carriers (63 presymptomatic and 37 symptomatic), and 239 non-carriers as controls. Linear mixed models were used to identify protein changes between the groups.
RESULT: Preliminary analysis reveals several significant differences between clinical groups and controls. As expected NEFL and GFAP show strong association with symptomatic individuals versus controls (adjusted p <0.001 for both). Notably, NPTXR and SNAP25 are significantly reduced in symptomatic participants compared to controls (FDR adjusted p <0.001 and p =0.003, respectively) and appear to have a genotype specific effect. NPTXR was reduced in GRN, C9orf72 and MAPT positive symptomatic individuals versus controls, whilst SNAP25 reduction appears more specific to GRN mutation carriers. Further analyses are underway to elucidate group differences and changes at presymptomatic stages as well as within pathology specific groups.
CONCLUSION: Our preliminary results show promising potential for the NULISA technology in the context of frontotemporal dementia and further analysis underway will provide useful information for the biomarker field.
PMID:41433632 | DOI:10.1002/alz70861_108554
UK DRI Authors
