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Alzheimer's & dementia (Amsterdam, Netherlands)
Published

Inflammation biomarkers and Alzheimer's disease: A pilot study using NULISAseq

Authors

Guglielmo Di Molfetta, Ilaria Pola, Kubra Tan, Richard Isaacson, Kaj Blennow, Nicholas J Ashton, Andrea L Benedet, Henrik Zetterberg

Abstract

Alzheimers Dement (Amst). 2025 Jan 30;17(1):e70079. doi: 10.1002/dad2.70079. eCollection 2025 Jan-Mar.

ABSTRACT

INTRODUCTION: Increasing evidence links amyloid beta (Aβ) aggregation with inflammation. This pilot study investigated the use of an immunoassay panel to map biomarker changes in patients with Alzheimer's disease (AD). Furthermore, we evaluated the stability of protein quantification after multiple freeze-thaw cycles (FTCs).

METHODS: The nucleic acid-linked immuno-sandwich assay (NULISA) inflammation panel measured 203 proteins in serum samples of individuals with (n = 31) and without (n = 31) AD pathology. Linear models, adjusted for age and sex, contrasted protein expression across groups.

RESULTS: After multiple-testing adjustments, glial fibrillary acidic protein (p < 0.001) and S100A12 (p < 0.001) were significantly changed in the presence of AD pathology. Furthermore, they correlated with cerebrospinal fluid biomarkers (phosphorylated tau-181 [p-tau181], tau, and Aβ42). Additional markers were nominally changed between groups. Five FTCs caused minimal changes in measurements with the NULISA inflammation panel.

DISCUSSION: Monitoring of inflammation in AD, using the 200-plex NULISA panel, demonstrates changes in peripherally circulating inflammation-related proteins. Contrary to previous reports, FTCs had minimal impact on the quantification of inflammatory markers.

HIGHLIGHTS: The novel nucleic acid-linked immuno-sandwich assay (NULISA) inflammation panel, which includes 200 protein biomarkers, was used.The panel was used for the first time in serum from patients with Alzheimer's disease (AD).The protein S100A12 was identified as a potential biomarker for AD.Inflammation markers were stable in up to five freeze-thaw cycles.

PMID:39886321 | PMC:PMC11780250 | DOI:10.1002/dad2.70079

UK DRI Authors

Profile picture of Henrik Zetterberg

Prof Henrik Zetterberg

Group Leader

Pioneering the development of fluid biomarkers for dementia

Prof Henrik Zetterberg