Serum Thioredoxin-80 is associated with age, ApoE4, and neuropathological biomarkers in Alzheimer’s disease: a potential early sign of AD
| العنوان: | Serum Thioredoxin-80 is associated with age, ApoE4, and neuropathological biomarkers in Alzheimer’s disease: a potential early sign of AD |
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| المؤلفون: | Julen Goikolea, Gorka Gerenu, Makrina Daniilidou, Francesca Mangialasche, Patrizia Mecocci, Tiia Ngandu, Juha Rinne, Alina Solomon, Miia Kivipelto, Angel Cedazo-Minguez, Anna Sandebring-Matton, Silvia Maioli |
| المصدر: | Addi. Archivo Digital para la Docencia y la Investigación instname |
| بيانات النشر: | BMC, 2022. |
| سنة النشر: | 2022 |
| مصطلحات موضوعية: | Amyloid beta-Peptides, Cognitive Neuroscience, Apolipoprotein E4, aging, tau Proteins, Alzheimer's disease, Thioredoxins, Neurology, Alzheimer Disease, inflammation, Humans, Cognitive Dysfunction, Neurology (clinical), Alzheimer’s disease, Biomarkers, Aged, Thioredoxin-80, dementia, apoE4 |
| الوصف: | Background Thioredoxin-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. Methods Trx80 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. Results In 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. Conclusion We 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 registration ClinicalTrials.govNCT01041989. Registered on 4 January 2010—retrospectively registered |
| وصف الملف: | application/pdf |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::51a4fdaaef8c0b040ebb335c0690d263Test http://hdl.handle.net/10810/56560Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....51a4fdaaef8c0b040ebb335c0690d263 |
| قاعدة البيانات: | OpenAIRE |
| الوصف غير متاح. |