Novel plasma biomarkers of amyloid plaque pathology and cortical thickness: Evaluation of the NULISA targeted proteomic platform in an ethnically diverse cohort

IF 13 1区医学 Q1 CLINICAL NEUROLOGY

Alzheimer's & Dementia Pub Date : 2025-02-24 DOI:10.1002/alz.14535

Xuemei Zeng, Anuradha Sehrawat, Tara K. Lafferty, Yijun Chen, Mahika Rawat, M. Ilyas Kamboh, Victor L. Villemagne, Oscar L. Lopez, Ann D. Cohen, Thomas K. Karikari

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Abstract

INTRODUCTION

Proteomic evaluation of plasma samples could accelerate the identification of novel Alzheimer's disease (AD) biomarkers. We evaluated the novel NUcleic acid Linked Immuno-Sandwich Assay (NULISA) proteomic method in an ethnically diverse cohort.

METHODS

Plasma biomarkers were measured with NULISA in the Human Connectome Project, a predominantly preclinical biracial community cohort in southwestern Pennsylvania. Selected biomarkers were additionally measured using Simoa and Quest immunoassays and compared.

RESULTS

On NULISA, phosphorylated tau (p-tau217, p-tau231, and p-tau181), glial fibrillary acidic protein (GFAP), and microtubule-associated protein tau (MAPT-tau) showed the top significant association with amyloid beta (Aβ) positron emission tomography (PET) status, followed by the neuroinflammation markers C-C motif ligand 2 (CCL2), chitotriosidase 1 (CHIT1) and interleukin-8 (CXCL8), and the synaptic marker neurogranin (NRGN). Biomarkers associated with cortical thickness included astrocytic protein chitinase-3-like protein 1 (CHI3L1), cytokine CD40 ligand (CD40LG), brain-derived neurotrophic factor (BDNF), the Aβ-associated metalloprotein TIMP3 (tissue inhibitor of metalloprotein 3), and ficolin 2 (FCN2). Furthermore, moderate to strong between-platform correlations were observed for various assays.

DISCUSSION

NULISA multiplexing advantage allowed concurrent assessment of established and novel plasma biomarkers of Aβ pathology and neurodegeneration.

Highlights

Classical Alzheimer's disease (AD) biomarkers measured using the NUcleic acid Linked Immuno-Sandwich Assay (NULISA) with next-generation sequencing readout (NULISAseq) CNS panel showed strong concordance with those measured using established immunoassay methods from Quanterix and Quest, with glial fibrillary acidic protein (GFAP) and neurofilament light (NfL) exhibiting the strongest correlation.
NULISAseq proteomic analysis identified several plasma biomarkers strongly associated with AD pathology in a biracial community cohort of older adults. Notably, phosphorylated tau-217 (p-tau217), GFAP, and p-tau231 displayed the strongest association with amyloid beta (Aβ) pathology, whereas brain-derived neurotrophic factor (BDNF) was strongly associated with neurodegeneration.
We demonstrate that plasma biomarker levels could be influenced by age, sex, apolipoprotein E (APOE) genotype, and self-identified race. Specifically, GFAP, NfL, and surfactant protein D (SFTPD) showed a strong association with age; CD63 and S100 calcium-binding protein B (S100B) with self-identified race; synaptosomal-associated protein 25 (SNAP25) with APOE genotype; and serum amyloid A1 (SAA1) and superoxide dismutase 1 (SOD1) with significant sex differences.

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来源期刊

Alzheimer's & Dementia 医学-临床神经学

CiteScore

14.50

自引率

5.00%

发文量

299

审稿时长

3 months

期刊介绍： Alzheimer's & Dementia is a peer-reviewed journal that aims to bridge knowledge gaps in dementia research by covering the entire spectrum, from basic science to clinical trials to social and behavioral investigations. It provides a platform for rapid communication of new findings and ideas, optimal translation of research into practical applications, increasing knowledge across diverse disciplines for early detection, diagnosis, and intervention, and identifying promising new research directions. In July 2008, Alzheimer's & Dementia was accepted for indexing by MEDLINE, recognizing its scientific merit and contribution to Alzheimer's research.