ArticleAlzheimer's & dementia : the journal of the Alzheimer's Association2025
Novel plasma biomarkers of amyloid plaque pathology and cortical thickness: Evaluation of the NULISA targeted proteomic platform in an ethnically diverse cohort.
Article in Alzheimer's & dementia : the journal of the Alzheimer's Association, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed.
- Blood-based biomarkers and early diagnosis of Alzheimer's disease.Neural regeneration research · 2026Article
- Cross-cohort NULISAseq identifies tau-anchored CSF and plasma-specific signatures across the amyloid-positive Alzheimer's disease.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026Article
- Dissecting Alzheimer's proteomic landscape through NULISA profiling of brain cell-specific extracellular vesicles.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026Article
- Beyond amyloid and tau: synaptic and neurodegenerative biomarkers shape MCI progression.Molecular psychiatry · 2026Article
- Biomarker Based ARIA Stress Test: A Proposed Conceptual Framework for Dynamic Biomarker-Guided ARIA Risk Stratification in Anti-Amyloid Immunotherapy for Alzheimer's Disease.Journal of molecular neuroscience : MN · 2026Review
- Proteomic analysis in Alzheimer's disease and other dementias: a focus on sex-specific differences.Alzheimer's research & therapy · 2026Article
- Plasma proteomic signatures of preclinical Alzheimer's disease in clinically unimpaired older adults.Molecular neurodegeneration · 2026Article
- Evaluation of serum as an alternative matrix to plasma for NULISA‑based proteomic blood biomarker measurements.Scientific reports · 2026Article
- Abnormalities in core AD biomarkers precede inflammatory and glial markers in CSF in Autosomal Dominant Alzheimer's Disease.medRxiv : the preprint server for health sciences · 2026Article
- Integration over reduction: multimodal PET and fluid biomarkers in Alzheimer's disease and beyond.Current opinion in neurology · 2026Review
- Review
- Plasma biomarkers, brain amyloid-beta pathology, and cortical thickness in a non-Hispanic White and Black/African American middle-aged community cohort: The HCP-CoBRA study.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2025Article
- Plasma vs. serum: which is better for proteomic blood biomarker analysis? Evaluation of the novel NULISA platform.medRxiv : the preprint server for health sciences · 2025Article
- A peripheral proteomic signature of Alzheimer's disease is identified in the plasma extracellular vesicles of mild cognitive impairment patients from a memory clinic: the BIOPEXAL study.Research square · 2025Article
- Plasma proteomic signatures of preclinical Alzheimer's disease biomarkers and memory in clinically unimpaired older adults.medRxiv : the preprint server for health sciences · 2025Article
- Pittsburgh plasma p-tau217: Classification accuracies for autosomal dominant and sporadic Alzheimer's disease in the community.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2025Article
- Glucose Metabolism, Lactate, Lactylation and Alzheimer's Disease.Aging and disease · 2025Review
- Novel plasma biomarkers of amyloid plaque pathology and cortical thickness: Evaluation of the NULISA targeted proteomic platform in an ethnically diverse cohort.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2025Article
- Cross-platform analytical assessment of serum GFAP quantification in multiple sclerosis: SIMOA versus two automated immunoassays.Frontiers in neurology · 2025Article
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Authors and funding
10 authors.
Funding
Abstract
introductionProteomic 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.
methodsPlasma 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.
resultsOn 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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