HAI Book 2025 - Flipbook - Page 708
Malpetti, Maura
Novel blood-based proteomic signatures across neurodegenerative
diseases
Robert Durcan1, Amanda Heslegrave2, Peter Swann1, Henrik Zetterberg2, John T O9Brien1,
James B Rowe1, Maura Malpetti1
1
University of Cambridge, Cambridge, GB
University College London, London, GB
2
Blood-based biomarkers offer a promising avenue for early and differential diagnosis in neurodegenerative
diseases. However, biomarkers are needed that bring together markers of proteinopathy with concomitant
pathophysiological processes, such as neuroinflammation and synaptic loss. This study evaluates a novel
multiplex proteomic method to identify differential diagnostic and prognostic markers in patients with
neurodegenerative diseases, including Alzheimer9s disease (AD), Lewy body dementia (LBD), frontotemporal
dementia (FTD) and progressive supranuclear palsy (PSP).
Serum samples from n=141 patients (MCI/AD=36, LBD=34, FTD=36, PSP=35) and n=29 age-matched controls were
analysed with the NUcleic acid Linked Immunosorbent Assay (NULISA) CNS panel. The panel measures ~120
analytes, including A´ peptides, p-tau isoforms, and markers of neurodegeneration, inflammation and vascular
health. NULISA markers were compared to p-tau217, p-tau231, GFAP, and NEFL measured using Single Molecule
Array (Simoa, n=158). Biomarkers were compared across groups with Linear Models for Microarray and RNA-Seq
Data Analyses (LIMMA) and finally used as predictors of survival in a Cox regression model, correcting for age and
sex.
NULISA markers were detected with high sensitivity (~94.1% target detectability), and like-for-like proteins
significantly correlated with Simoa counterparts (r=0.6-0.9, p
LBD). LBD showed higher
levels of neuropentraxins (NPTX1/2) than AD/MCI (Fig.2A). NEFL was most elevated in FTD and PSP compared to
controls, alongside multiple cytokines and chemokines. PSP showed higher levels of inflammation-related
markers, including IL7, CX3CL1, and periostin than FTD, where higher levels of fibroblast growth factor 2 were
observed. NEFL predicted survival (Fig.2B).
The NULISA CNS-panel demonstrates high sensitivity and reliability for detecting multiple biomarkers across
neurodegenerative disorders. It revealed distinct condition-specific profiles, with NEFL emerging as a key
outcome predictor. This multiplex approach offers potential for differential diagnosis and targets identification,
beyond commonly used dementia-related markers.
HAI2025 - 708
