Diagnostic utility of GDF15 in neurodegenerative diseases: A systematic review and meta‐analysis

Abstract

Introduction: GDF15 may be a potential biomarker for neurodegenerative diseases. In this analysis, we aimed to quantitative analysis the levels of GDF15 in patients with neurological diseases and in health control, and then to determine its potential diagnostic utility.Methods: Two researchers separately conducted a systematic search of the relevant studies up to January 2021 in Embase, PubMed, and Web of Science. Effect sizes were estimated to use the standardized mean difference (SMD) with 95% confidence interval (CI). Sensitivity and specificity were calculated by the summary receiver operating characteristics curve (SROC) method. The sensitivity analysis was performed by the "one-in/one-out" approach. Considering the considerable heterogeneity among studies, random-effects model was used for the meta-analysis investigation.Results: A total of eight articles were included in this meta-analysis and systematic review. The pooled results of the random effect model indicated GDF15 levels were significantly higher in patients with neurodegenerative disease than healthy people (SMD = 0.92, 95% CI: 0.44-1.40, Z = 3.75, p < 0.001). Sensitivity and specificity of biomarker of GDF15 were 0.90 (95% CI: 0.75-0.97), 0.77 (95% CI: 0.67-0.65), and AUC = 0.87 (95% CI: 0.84-0.90), respectively. Conclusions: GDF15 levels were higher in patients with neurodegenerative disease than healthy people. And serum levels of GDF15 were a better marker for diagnostic utility of neurodegenerative disease.

The expression pattern of GDF15 in human brain changes during aging and in Alzheimer’s disease

“…Finally, and contrary to expectations, CSF levels of GDF15 are not different between AD patients and non-AD subjects, but are strongly associated with plasma GDF15 levels. This was the first step of the present work, as previous studies have found an association between the circulating levels of GDF15 and the risk of dementia, cerebrovascular disease, cognitive impairment as well as brain atrophy, and AD ( Fuchs et al, 2013 ; Chai et al, 2016 ; Jiang et al, 2016 ; Nasrabady et al, 2018 ; Wu et al, 2021 ; Xue et al, 2022 ). We were not able to confirm these data in a previous study that analyzed the plasma of 120 AD patients as compared with 194 age-matched controls including 102 offspring of centenarians, who are considered to be a model of successful aging ( Conte et al, 2021 ).…”

“…Several studies in humans have found an association between high circulating levels of GDF15 and the risk of dementia, cerebrovascular disease, cognitive impairment, and brain atrophy, which are clinical features of many neurodegenerative diseases ( Fuchs et al, 2013 ; Chai et al, 2016 ; Jiang et al, 2016 ; Nasrabady et al, 2018 ). In particular, some studies suggested that high circulating levels of GDF15 are associated with the risk of developing AD, as well as other neurodegenerative diseases, and considered this protein as a promising diagnostic biomarker and therapeutic target of several neurodegenerative diseases ( Chai et al, 2016 ; Wu et al, 2021 ; Xue et al, 2022 ). On the other hand, other studies have found no difference in the circulating level of GDF15 in AD patients compared to age-matched healthy controls ( Conte et al, 2021 ), or showed that exogenous recombinant GDF15 can promote Aβ clearance activity of microglial cultured cells ( Kim et al, 2018 ).…”

Association of Motoric Cognitive Risk Syndrome with Sarcopenia and Systemic Inflammation in Pre-Frail Older Adults

“…GDF-15, also known as macrophage inhibitory cytokine-1, is expressed in most organs, including damaged neurons, and it is a marker of mitochondrial dysfunction and elevated in myopathies and neurodegenerative disease [ 66 ]. It has both a protective effect, where it plays a role in modulating immune function and improving insulin sensitivity, as well as a negative systemic effect, where it serves as a prognostic biomarker for cancer and cardiovascular disease [ 31 , 66 ]. GDF-15 is known to be associated with slow gait and functional impairment [ 31 ].…”

Mitochondrial Stress Links Environmental Triggers with Pro-Inflammatory Signaling in Crohn’s Disease

“…As a mitokine, levels of GDF15 are increased upon mitochondrial stress [23]. However, increased levels of GDF15 are found not only in primary mitochondrial disorders [24] but also in different diseases like neurodegenerative diseases [25], cardiovascular diseases [26], and cancer [27]. Furthermore, GDF15 is elevated in conditions like aging [28] or exercise [29].…”