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

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 af...

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Main Authors: Guglielmo Di Molfetta, Ilaria Pola, Kubra Tan, Richard Isaacson, Kaj Blennow, Nicholas J. Ashton, Andrea L. Benedet, Henrik Zetterberg
Format: Article
Language:English
Published: Wiley 2025-01-01
Series:Alzheimer’s & Dementia: Diagnosis, Assessment & Disease Monitoring
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Online Access:https://doi.org/10.1002/dad2.70079
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author Guglielmo Di Molfetta
Ilaria Pola
Kubra Tan
Richard Isaacson
Kaj Blennow
Nicholas J. Ashton
Andrea L. Benedet
Henrik Zetterberg
author_facet Guglielmo Di Molfetta
Ilaria Pola
Kubra Tan
Richard Isaacson
Kaj Blennow
Nicholas J. Ashton
Andrea L. Benedet
Henrik Zetterberg
author_sort Guglielmo Di Molfetta
collection DOAJ
description 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.
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spelling doaj-art-4a413300f53a4b6d8f5cf818da66384a2025-08-20T02:49:22ZengWileyAlzheimer’s & Dementia: Diagnosis, Assessment & Disease Monitoring2352-87292025-01-01171n/an/a10.1002/dad2.70079Inflammation biomarkers and Alzheimer's disease: A pilot study using NULISAseqGuglielmo Di Molfetta0Ilaria Pola1Kubra Tan2Richard Isaacson3Kaj Blennow4Nicholas J. Ashton5Andrea L. Benedet6Henrik Zetterberg7Department of Psychiatry and Neurochemistry Institute of Neuroscience & Physiology The Sahlgrenska Academy at the University of Gothenburg Mölndal SwedenDepartment of Psychiatry and Neurochemistry Institute of Neuroscience & Physiology The Sahlgrenska Academy at the University of Gothenburg Mölndal SwedenDepartment of Psychiatry and Neurochemistry Institute of Neuroscience & Physiology The Sahlgrenska Academy at the University of Gothenburg Mölndal SwedenDepartment of Neurology Weill Cornell Medicine and New York‐Presbyterian New York New York USADepartment of Psychiatry and Neurochemistry Institute of Neuroscience & Physiology The Sahlgrenska Academy at the University of Gothenburg Mölndal SwedenDepartment of Psychiatry and Neurochemistry Institute of Neuroscience & Physiology The Sahlgrenska Academy at the University of Gothenburg Mölndal SwedenDepartment of Psychiatry and Neurochemistry Institute of Neuroscience & Physiology The Sahlgrenska Academy at the University of Gothenburg Mölndal SwedenDepartment of Psychiatry and Neurochemistry Institute of Neuroscience & Physiology The Sahlgrenska Academy at the University of Gothenburg Mölndal SwedenAbstract 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.https://doi.org/10.1002/dad2.70079freeze–thaw cyclesGFAPinflammationmultiplexed‐immunoassaysnovel blood biomarkersNULISA
spellingShingle Guglielmo Di Molfetta
Ilaria Pola
Kubra Tan
Richard Isaacson
Kaj Blennow
Nicholas J. Ashton
Andrea L. Benedet
Henrik Zetterberg
Inflammation biomarkers and Alzheimer's disease: A pilot study using NULISAseq
Alzheimer’s & Dementia: Diagnosis, Assessment & Disease Monitoring
freeze–thaw cycles
GFAP
inflammation
multiplexed‐immunoassays
novel blood biomarkers
NULISA
title Inflammation biomarkers and Alzheimer's disease: A pilot study using NULISAseq
title_full Inflammation biomarkers and Alzheimer's disease: A pilot study using NULISAseq
title_fullStr Inflammation biomarkers and Alzheimer's disease: A pilot study using NULISAseq
title_full_unstemmed Inflammation biomarkers and Alzheimer's disease: A pilot study using NULISAseq
title_short Inflammation biomarkers and Alzheimer's disease: A pilot study using NULISAseq
title_sort inflammation biomarkers and alzheimer s disease a pilot study using nulisaseq
topic freeze–thaw cycles
GFAP
inflammation
multiplexed‐immunoassays
novel blood biomarkers
NULISA
url https://doi.org/10.1002/dad2.70079
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