ArticleAlzheimer's research & therapy2022
Serum Thioredoxin-80 is associated with age, ApoE4, and neuropathological biomarkers in Alzheimer's disease: a potential early sign of AD.
Article in Alzheimer's research & therapy, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT01041989 (Finnish Geriatric Intervention Study to Prevent Cognitive Impairment and Disability), which is not on this map. Cited by 9 papers.
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Finnish Geriatric Intervention Study to Prevent Cognitive Impairment and Disability
Who cites it
9 citing papers in PubMed, 15 citations in OpenAlex.
- Crosstalk of thioredoxin system and programmed cell death: from pathophysiology to novel therapy.Redox biology · 2026Review
- Revealing Metabolic Reprogramming Genes as Biomarkers of Rheumatoid Arthritis: A Bioinformatics Study Based on Ensemble Learning Approach and Single Cell RNA Sequencing.Endocrine, metabolic & immune disorders drug targets · 2026Article
- Thioredoxin (Trx): A redox target and modulator of cellular senescence and aging-related diseases.Redox biology · 2024Review
- The interaction between ageing and Alzheimer's disease: insights from the hallmarks of ageing.Translational neurodegeneration · 2024Review
- SIRT2 Inhibition Rescues Neurodegenerative Pathology but Increases Systemic Inflammation in a Transgenic Mouse Model of Alzheimer's Disease.Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology · 2023Article
- Sting and p53 DNA repair pathways are compromised in Alzheimer's disease.Scientific reports · 2023Article
- Alzheimer's disease biomarker profiling in a memory clinic cohort without common comorbidities.Brain communications · 2023Article
- Precision medicine in neurodegeneration: the IHI-PROMINENT project.Frontiers in neurology · 2023Article
- TNF-α and IL-1β Modulate Blood-Brain Barrier Permeability and Decrease Amyloid-β Peptide Efflux in a Human Blood-Brain Barrier Model.International journal of molecular sciences · 2022Article
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Authors and funding
12 authors at 6 institutions in 5 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundThioredoxin-80 (Trx80) is a cleavage product from the redox-active protein Thioredoxin-1 and has been previously described as a pro-inflammatory cytokine secreted by immune cells. Previous studies in our group reported that Trx80 levels are depleted in Alzheimer's disease (AD) brains. However, no studies so far have investigated peripheral Trx80 levels in the context of AD pathology and whether could be associated with the main known AD risk factors and biomarkers.
methodsTrx80 was measured in serum samples from participants from two different cohorts: the observational memory clinic biobank (GEDOC) (N = 99) with AD CSF biomarker data was available and the population-based lifestyle multidomain intervention trial Finnish Geriatric Intervention Study to Prevent Cognitive Impairment and Disability (FINGER) (N = 47), with neuroimaging data and blood markers of inflammation available. The GEDOC cohort consists of participants diagnosed with subjective cognitive impairment (SCI), mild cognitive impairment (MCI), and AD, whereas the FINGER participants are older adults at-risk of dementia, but without substantial cognitive impairment. One-way ANOVA and multiple comparison tests were used to assess the levels of Trx80 between groups. Linear regression models were used to explore associations of Trx80 with cognition, AD CSF biomarkers (Aβ42, t-tau, p-tau and p-tau/t-tau ratio), inflammatory cytokines, and neuroimaging markers.
resultsIn the GEDOC cohort, Trx80 was associated to p-tau/t-tau ratio in the MCI group. In the FINGER cohort, serum Trx80 levels correlated with lower hippocampal volume and higher pro-inflammatory cytokine levels. In both GEDOC and FINGER cohorts, ApoE4 carriers had significantly higher serum Trx80 levels compared to non-ApoE4 carriers. However, Trx80 levels in the brain were further decreased in AD patients with ApoE4 genotype.
conclusionWe report that serum Trx80 levels are associated to AD disease stage as well as to several risk factors for AD such as age and ApoE4 genotype, which suggests that Trx80 could have potential as serum AD biomarker. Increased serum Trx80 and decreased brain Trx80 levels was particularly seen in ApoE4 carriers. Whether this could contribute to the mechanism by which ApoE4 show increased vulnerability to develop AD would need to be further investigated.
trial registrationClinicalTrials.gov NCT01041989 . Registered on 4 January 2010-retrospectively registered.
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