Pathophysiological implications of actin-free Gc-globulin concentration changes in blood plasma and cerebrospinal fluid collected from patients with Alzheimer’s disease and other neurological disorders

Kułakowska, Alina; Tarasiuk, Joanna; Kapica-Topczewska, Katarzyna; Chorąży, Monika; Pogorzelski, Robert; Kulczyńska-Przybik, Agnieszka; Mroczko, Barbara; Bucki, Robert

doi:10.17219/acem/70441

Cited by 7 publications

(10 citation statements)

References 36 publications

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“…The differences between VDBP concentrations in the various studies could be the result of variation between numbers of male and female patients and controls included in these studies or by using either a polyclonal or monoclonal assay. It is known that VDBP can affect inflammatory processes [22,23,25,26,61,69,70]. As we found higher VDBP in male MS patients, in the presence of a similar EDSS score as in female MS patients, this suggests a possible modulating effect of VDBP in male MS patients.…”

Section: Discussionsupporting

confidence: 71%

Multiple Sclerosis Patients Show Lower Bioavailable 25(OH)D and 1,25(OH)2D, but No Difference in Ratio of 25(OH)D/24,25(OH)2D and FGF23 Concentrations

Vlot

Boekel²,

Kragt

et al. 2019

Nutrients

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Vitamin D (VitD) insufficiency is common in multiple sclerosis (MS). VitD has possible anti-inflammatory effects on the immune system. The ratio between VitD metabolites in MS patients and the severity of the disease are suggested to be related. However, the exact effect of the bone-derived hormone fibroblast-growth-factor-23 (FGF23) and VitD binding protein (VDBP) on this ratio is not fully elucidated yet. Therefore, the aim is to study differences in total, free, and bioavailable VD metabolites and FGF23 between MS patients and healthy controls (HCs). FGF23, vitD (25(OH)D), active vitD (1,25(OH)2D), inactive 24,25(OH)D, and VDBP were measured in 91 MS patients and 92 HCs. Bioavailable and free concentrations were calculated. No difference in FGF23 (p = 0.65) and 25(OH)D/24.25(OH)2D ratio (p = 0.21) between MS patients and HCs was observed. Bioavailable 25(OH)D and bioavailable 1.25(OH)2D were lower (p < 0.01), while VDBP concentrations were higher in MS patients (p = 0.02) compared with HCs, specifically in male MS patients (p = 0.01). In conclusion, FGF23 and 25(OH)D/24.25(OH)2D did not differ between MS patients and HCs, yet bioavailable VitD concentrations are of potential clinical relevance in MS patients. The possible immunomodulating role of VDBP and gender-related differences in the VD-FGF23 axis in MS need further study.

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Section: Discussionsupporting

confidence: 71%

Multiple Sclerosis Patients Show Lower Bioavailable 25(OH)D and 1,25(OH)2D, but No Difference in Ratio of 25(OH)D/24,25(OH)2D and FGF23 Concentrations

Vlot

Boekel²,

Kragt

et al. 2019

Nutrients

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“…This technology is a multiplexed, aptamer-based assay that allows the simultaneous quantification of a large amount of proteins [ 161 ]. Targeted studies were carried out mostly by Enzyme-Linked Immuno-Sorbent Assay (ELISA) [ 162 - 164 ] or other immunoassays [ 129 , 165 ]. The second group of analytical tools used for protein targeted determinations is based on western blot [ 166 - 170 ].…”

Section: Resultsmentioning

confidence: 99%

“…In addition, other inflammatory proteins, such as interleukins or TNF-α, seemed to be good biomarkers for AD diagnosis, showing a correlation with cognitive alterations since early AD stages [ 223 - 225 ]. Also, globulins such as β2-microglobulin and γc-globulin have been related to AD [ 162 , 184 ]. Moreover, a panel of 33 proteins, mainly related to inflammation, permitted the development of a multivariate diagnosis model for AD with an AUC close to 100% [ 172 ].…”

Section: Resultsmentioning

confidence: 99%

Recent Evidence in Epigenomics and Proteomics Biomarkers for Early and Minimally Invasive Diagnosis of Alzheimer’s and Parkinson’s Diseases

Mayo

Benito‐León

Peña-Bautista

et al. 2021

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Background: Alzheimer’s (AD) and Parkinson’s diseases (PD) show deposits of improperly folded modified proteins, so protein expression mechanisms are involved since early stages. Several studies evaluated epigenomics and proteomics profiles in these patients, with promising results. In general, they focused on early, specific, and minimally invasive biomarkers for diagnosis and prognosis of AD and PD. Objectives: This review aimed at summarizing results to find the most reliable evidence in the field. Method: A PubMed search was carried out. It was limited to the last 6 years, using a combination of search terms related to AD, PD and epigenetics or proteomics. Results: Among epigenomics studies, most of them focused on microRNAs (miRNAs) as candidate diagnosis biomarkers for AD or PD from blood samples like miR-342-3p, miR-107, miR-106a-5p, miR-106b-5p, miR-195, and miR-19b. In addition, the DNA methylation has been tested in a few works, obtaining significant differences in some genes (NCAPH2/LMF2 COASY, SPINT1, BDNFTREM1, TREM2, NPAS2, PDE4D), which could be useful for evaluating the disease progression as well as potential risk factors. Regarding proteomics, most of the studies were untargeted and used plasma or serum samples. In general, they highlighted the importance of coagulation, inflammation pathways, and oxidative stress. Among targeted studies, some proteins (phosphorylated tau, C reactive protein (CRP), interleukins, necrosis factors, transferrin, glial fibrillary acidic protein (GFAP),and neurofilaments) showed different plasma levels in AD and PD patients in comparison with healthy participants. Finally, a few studies have identified specific-AD and PD epigenetic and proteomic biomarkers (ApoE and oxidized DJ-1) in comparison with other similar pathologies. Conclusion: In general, there is a common lack of clinical validation of these potential biomarkers, for which its use in the clinical practice is still limited.

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“…Another study proposed that the elevated circulating concentrations of G-actin underly the post-injury reduction in DNase activity [ 42 ]. Furthermore, the chronic nature of neurodegenerative disease may initiate a compensatory Gc-globulin increase as a response to elevated levels of actin [ 43 ]. Therefore, such a biomarker that increases with the disease progression (as in the present study) is of the highest value when it comes to a diagnostic, and it calls for the pursuit of a validation study in a separate cohort.…”

Section: Discussionmentioning

confidence: 99%

Multi-Omics, an Integrated Approach to Identify Novel Blood Biomarkers of Alzheimer’s Disease

et al. 2022

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The metabolomic and proteomic basis of mild cognitive impairment (MCI) and Alzheimer’s disease (AD) is poorly understood, and the relationships between systemic abnormalities in metabolism and AD/MCI pathogenesis is unclear. This study compared the metabolomic and proteomic signature of plasma from cognitively normal (CN) and dementia patients diagnosed with MCI or AD, to identify specific cellular pathways and new biomarkers altered with the progression of the disease. We analysed 80 plasma samples from individuals with MCI or AD, as well as age- and gender-matched CN individuals, by utilising mass spectrometry methods and data analyses that included combined pathway analysis and model predictions. Several proteins clearly identified AD from the MCI and CN groups and included plasma actins, mannan-binding lectin serine protease 1, serum amyloid A2, fibronectin and extracellular matrix protein 1 and Keratin 9. The integrated pathway analysis showed various metabolic pathways were affected in AD, such as the arginine, alanine, aspartate, glutamate and pyruvate metabolism pathways. Therefore, our multi-omics approach identified novel plasma biomarkers for the MCI and AD groups, identified changes in metabolic processes, and may form the basis of a biomarker panel for stratifying dementia participants in future clinical trials.

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Pathophysiological implications of actin-free Gc-globulin concentration changes in blood plasma and cerebrospinal fluid collected from patients with Alzheimer’s disease and other neurological disorders

Abstract: Higher concentrations of free Gc-globulin in blood plasma and CSF collected from patients suffering from neurodegenerative diseases may indicate a potential role of this protein in their pathogenesis, and represent a potential tool for the diagnosis of CNS diseases.

Cited by 7 publications

References 36 publications

Multiple Sclerosis Patients Show Lower Bioavailable 25(OH)D and 1,25(OH)2D, but No Difference in Ratio of 25(OH)D/24,25(OH)2D and FGF23 Concentrations

Multiple Sclerosis Patients Show Lower Bioavailable 25(OH)D and 1,25(OH)2D, but No Difference in Ratio of 25(OH)D/24,25(OH)2D and FGF23 Concentrations

Recent Evidence in Epigenomics and Proteomics Biomarkers for Early and Minimally Invasive Diagnosis of Alzheimer’s and Parkinson’s Diseases

Multi-Omics, an Integrated Approach to Identify Novel Blood Biomarkers of Alzheimer’s Disease

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