ArticleMolecular psychiatry2017
Alpha-2 macroglobulin in Alzheimer's disease: a marker of neuronal injury through the RCAN1 pathway.
Article in Molecular psychiatry, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 82 papers, 1 of them a synthesis that pooled it.
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82 citing papers in PubMed, 1 synthesis or guideline pooled it, 141 citations in OpenAlex.
- Blood Plasma Proteome: A Meta-Analysis of the Results of Protein Quantification in Human Blood by Targeted Mass Spectrometry.International journal of molecular sciences · 2023Pooled it
- Trial
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- Exploring automated plasma phospho-tau217 assays for the diagnosis of Down syndrome-related Alzheimer's disease.Communications medicine · 2026Article
- When Viruses Talk through Extracellular Vesicles: a New Perspective on Sars-Cov-2-Induced Neurodegeneration.Journal of extracellular vesicles · 2026Article
- The Association Between Serum Copper Levels and Proteomics in Mild Cognitive Impairment.Nutrients · 2026Article
- Intracellular Signaling Regulated by Activated αInternational journal of molecular sciences · 2026Review
- PRPF8-associated retinitis pigmentosa variant induces human neural retina-autonomous photoreceptor defects.Scientific reports · 2026Article
- Review
- CGRP/TSP1 Signaling Dampens Corneal Inflammation and Fibrosis by Targeting A2M During Corneal Stromal Wound Healing.Investigative ophthalmology & visual science · 2026Article
- Spatial transcriptomics on an expanded dataset at the brain-electrode interface: exploration of variability and identification of novel biomarkers.Frontiers in neuroscience · 2026Article
- Proteome-Based Biomarkers for Alzheimer's Disease: Old Acquisitions and Innovative Proposals.International journal of molecular sciences · 2025Review
- Deciphering the role of complement system genes in pancreatic cancer susceptibility and prognosis.Nature communications · 2025Article
- Intercellular signaling and synaptic deconstruction uncovered by single-cell and spatial transcriptomics in an AD tauopathy model.Communications biology · 2025Article
- Bridging the barrier: insights into blood biomarkers and therapeutic strategies targeting choroid plexus and BBB dysfunction in alzheimer's disease.Biomarker research · 2025Review
- Monkeypox virus spreads from cell-to-cell and leads to neuronal death in human neural organoids.Nature communications · 2025Article
- Chronic sleep curtailment expediates brain aging by activating the complement and coagulation cascades in mice.bioRxiv : the preprint server for biology · 2025Article
- Novel Genes Associated With Working Memory Are Identified by Combining Connectome, Transcriptome, and Genome.Human brain mapping · 2025Article
- Single-microglia transcriptomic transition network-based prediction and real-world patient data validation identifies ketorolac as a repurposable drug for Alzheimer's disease.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2025Article
- Predicting Alzheimer's disease subtypes and understanding their molecular characteristics in living patients with transcriptomic trajectory profiling.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2025Article
22 more citing papers are in PubMed but not listed here.
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Authors and funding
18 authors at 7 institutions in 2 countries.
Funding
Abstract
Preclinical changes that precede the onset of symptoms and eventual diagnosis of Alzheimer's disease (AD) are a target for potential preventive interventions. A large body of evidence suggests that inflammation is closely associated with AD pathogenesis and may be a promising target pathway for such interventions. However, little is known about the association between systemic inflammation and preclinical AD pathophysiology. We first examined whether the acute-phase protein, alpha-2 macroglobulin (A2M), a major component of the innate immune system, was associated with cerebrospinal fluid (CSF) markers of neuronal injury in preclinical AD and risk of incident AD in the predictors of cognitive decline among normal individuals (BIOCARD) cohort. We find that A2M concentration in blood is significantly associated with CSF concentrations of the neuronal injury markers, tau and phosphorylated tau, and that higher baseline serum A2M concentration is associated with an almost threefold greater risk of progression to clinical symptoms of AD in men. These findings were replicated in the Alzheimer's Disease Neuroimaging (ADNI) study. Then, utilizing a systems level approach combining large multi-tissue gene expression datasets with mass spectrometry-based proteomic analyses of brain tissue, we identified an A2M gene network that includes regulator of calcineurin (RCAN1), an inhibitor of calcineurin, a well-characterized tau phosphatase. A2M gene and protein expression in the brain were significantly associated with gene and protein expression levels of calcineurin. Collectively these novel findings suggest that A2M is associated with preclinical AD, reflects early neuronal injury in the disease course and may be responsive to tau phosphorylation in the brain through the RCAN1-calcineurin pathway.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.