Biomarkers

Neuroinflammation is involved in the pathophysiology of several neurodegenerative diseases and has been linked to faster clinical decline. This study evaluates a novel multiplex proteomic method to assess blood-based inflammation patterns in patients with neurodegenerative diseases, including Alzheimer's disease (AD), Lewy body dementia (LBD), frontotemporal dementia (FTD) and progressive supranuclear palsy (PSP).

Serum samples from n = 137 patients (AD/MCI+=36, LBD=33, FTD=35, PSP=33) and n = 29 age-matched controls were analysed with the NUcleic acid Linked Immunosorbent Assay (NULISA) Inflammation 250 panel. The panel measures ∼250 analytes, including Glial fibrillary acidic protein (GFAP) and other biomarkers of inflammation and immune response. GFAP levels were comapared across groups with a Kruskal-Wallis test. All 250 biomarkers were compared across groups with Linear Models for Microarray and RNA-Seq Data Analyses (LIMMA), correcting for age and sex.

Serum levels of GFAP were increased especially in patients with AD/MCI+ and LBD and to a lower extent in patients with PSP (Figure 1). Considering all 250 markers, patients with AD/MCI+ showed increased GFAP levels as compared to controls over and above other markers (Figure 2A). Comparing each patient group to the AD/MCI+ cohort, patients with LBD had a larger number of markers being upregulated than AD/MCI+ (Figure 2B), including Granzyme Β (GZMB) and Lysosome-associated membrane glycoprotein 3 (LAMP-3). Patients with FTD (Figure 2C) and PSP (Figure 2D) had higher levels in several inflammation markers as compared to AD/MCI+, including Matrix metalloproteinase-9 (MMP9) and Hepatocyte Growth Factor (HGF).

The NULISA Inflammation 250 panel demonstrates high sensitivity for detecting inflammatory patterns across neurodegenerative disorders. It revealed distinct condition-specific profiles. Patients with LBD, FTD and PSP showed upregulation of many inflammation markers, as compared to controls and patients with AD.