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The growth-associated protein 43 (GAP-43) is a presynaptic phosphoprotein in cerebrospinal fluid (CSF). The ε4 allele of apolipoprotein E (APOE) is an important genetic risk factor for Alzheimer's disease (AD). We aimed to evaluate the association of CSF GAP-43 with cognition and whether this correlation was related to the APOE ε4 status. We recruited participants from the Alzheimer's Disease Neuroimaging Initiative (ADNI) database, and they were divided into cognitively normal (CN) ε4 negative (CN ε4−), CN ε4 positive (CN ε4+), mild cognitive impairment (MCI) ε4 negative (MCI ε4−), MCI ε4 positive (MCI ε4+), AD ε4 negative (AD ε4−), and AD ε4 positive (AD ε4+) groups. Spearman's correlation was utilized to evaluate the relationship between CSF GAP-43 and core AD biomarkers at the baseline. We performed receiver-operating characteristic (ROC) curve analyses to investigate the diagnostic accuracy of CSF GAP-43. The correlations between CSF GAP-43 and the Mini-Mental State Examination (MMSE) scores and brain atrophy at baseline were assessed by using multiple linear regression, while the association between CSF GAP-43 and MMSE scores at the follow-up was tested by performing the generalized estimating equation (GEE). The role of CSF GAP-43 in the conversion from MCI to AD was evaluated using the Cox proportional hazard model. We found that the CSF GAP-43 level was significantly increased in MCI ε4+, AD ε4− and AD ε4+ groups compared with CN ε4− or MCI ε4− group. The negative associations between the CSF GAP-43 and MMSE scores at the baseline and follow-up were found in MCI ε4− and MCI ε4+ groups. In addition, baseline CSF GAP-43 was able to predict the clinical progression from MCI to AD. CSF GAP-43 may be a promising biomarker to screen cognition for AD. The effects of CSF GAP-43 on cognition were suspected to be relevant to APOE ε4 status. [ABSTRACT FROM AUTHOR]

Ectodysplasin A (EDA), a new hepatokine, may be involved in energy metabolism. This study aims to 1) investigate the role of EDA in hepatic steatosis in C57BL/6 mice and HepG2 cells; 2) evaluate serum EDA in nonalcoholic fatty liver disease (NAFLD) in human. This study comprises an experimental study in vitro and in vivo and a hospital based case-control study. Western blotting, qPCR and ELISA were used to measure EDA levels. siRNA and shRNA were performed to knockdown EDA. An Adipokine Magnetic Bead Panel was performed to measure serum adipokines. Increased levels of hepatic and secreted EDA were detected in steatosis, in vivo and in vitro. Steatosis was ameliorated by EDA knockdown in vitro , while intrahepatic triglycerides content and liver enzymes were improved in vivo. Furthermore, knockdown of EDA upregulated lipolytic genes and suppressed lipogenic genes. Serum EDA in subjects with NAFLD was higher. Moreover, it reveals associations between circulating EDA and higher odds of NAFLD, while circulating EDA presented a practicable performance to identify NAFLD. Lastly, serum EDA level was dependent on BMI, TNF-α, T2DM and obesity. EDA aggravates steatosis by striking balance between lipid deposition and elimination. It was a potential biomarker of NAFLD. • Ectodysplasin A (EDA), a new hepatokine, involves in energy metabolism. • The role of EDA was evaluated in hepatic steatosis in C57BL/6 mice and HepG2 cells. • Circulating EDA was measured in a hospital-based case-control study. • EDA aggravates steatosis by striking balance of lipid deposition and elimination. • It suggests circulating EDA as a biomarker for non-alcoholic fatty liver disease. [ABSTRACT FROM AUTHOR]

Background CTRP3, a novel adipokine, has been linked with a variety of physiological functions, including adipokines secretion, energy metabolism, through an endocrine mean. This study evaluated the role of serum CTRP3 levels in the development of nonalcoholic fatty liver disease (NAFLD). Methods The hospital-based longitudinal study recruited urban residents who took health examination. Serum CTRP3 levels were evaluated by an enzyme-linked immunosorbent assay. The adjusted odds ratio (OR) and 95% confidence interval (CI) were calculated to assess the relationship between baseline serum CTRP3 and incidence of NAFLD at follow-up. Results Of the 814 participants at baseline, 313 subjects were included at follow-up. At baseline, serum CTRP3 level was lower in subjects with NAFLD (283.3 [159.6–375.0] ng/ml) than it in non-NAFLD subjects (295.0 [184.0–398.0] ng/ml) ( p = 0.006). Meanwhile, serum CTRP3 level was inversely correlated with body mass index, waist-to-hip ratio, triglycerides and fasting plasma glucose. After a 3-y follow-up, the CTRP3 concentrations decreased from the baseline (206.7 [136.3–322.6] ng/ml) to the follow-up (177.4 [112.1–295.5] ng/ml, p < 0.001) in the subjects who developed NAFLD ( n = 55). Compared with the 1st Quartile of baseline serum CTRP3, the subjects in the 3rd Quartile and 4th Quartile indicated lower risks of NAFLD progression at 3-y (adjusted OR = 0.451, 95% CI [0.270–0.755], p = 0.002 and adjusted OR = 0.468, 95% CI [0.310–0.707], p < 0.001). Conclusion Serum level of CTRP3 was inversely associated with the progress of NAFLD independently at 3-y. [ABSTRACT FROM AUTHOR]