Association of Adipokines with Alzheimer's Disease in a Chinese Cohort.

BACKGROUND: The correlation between plasma adipose factor levels and Alzheimer's patients is not entirely clear. OBJECTIVE: We aimed to investigate associations between AD and plasma levels of three adipokines including plasma adiponectin, leptin, and resistin. METHODS: A single-center, cross-sectional study recruited AD patients (n = 148) and cognitively normal (CN) controls (n = 110). The multivariate logistic regression analysis was applied to determine associations of adiponectin, leptin, and resistin with the presence of AD. The receiver operating characteristic (ROC) analysis was employed to determine the diagnostic power of adiponectin, leptin and resistin for AD. RESULTS: After adjusted for the conventional risk factors, plasma levels of leptin (OR = 0.417, 95% CI: 0.272-0.638, p < 0.0001) and adiponectin (OR = 1.249, 95% CI: 1.151-1.354, p < 0.0001) were associated with the presence of AD. In total participants, the plasma adiponectin level was negatively correlated with MMSE scores (p < 0.0001) and was positively with CDR scores (p < 0.0001) and age (p < 0.0001). The plasma level of leptin was negatively correlated with CDR scores (p < 0.0001) and positively correlated with MMSE scores (p < 0.0001). Both adiponectin (p < 0. 0001) and leptin (p < 0. 0001) featured higher AUC than the random chance. CONCLUSIONS: Plasma adiponectin and leptin were associated with the presence, symptomatic severity, and diagnostic power of AD, suggesting a potential role of adipokines in the pathogenesis of AD.

Circulating Naturally Occurring Antibodies to P2RY2 Are Decreased in Alzheimer's Disease.

BACKGROUND: The G protein-coupled receptor P2RY2 protein of the purinergic receptor family is involved in the pathogenesis of Alzheimer's disease (AD). Naturally occurring antibodies against P2RY2 (NAbs-P2RY2) are present in human plasma, with their clinical relevance in AD unknown. OBJECTIVE: To explore the alteration of NAbs-P2RY2 in AD patients and its associations with biomarkers and cognition of AD patients. METHODS: The levels of naturally occurring antibodies against the four extracellular domains of P2RY2 (NAbs-P2RY2-1, NAbs-P2RY2-2, NAbs-P2RY2-3, and NAbs-P2RY2-4) were measured in the plasma of 55 AD patients, 28 non-AD dementia patients, and 70 cognitively normal participants. The correlations of autoantibody levels with cognitive scale scores, AD plasma biomarkers, and brain amyloid burden were examined. RESULTS: NAbs-P2RY2-1, NAbs-P2RY2-3, and NAbs-P2RY2-4 were reduced in AD patients. Plasma levels of NAbs-P2RY2-2 and NAbs-P2RY2-3 levels were positively associated with cognitive and functional performances. Among these antibodies, plasma NAbs-P2RY2-2 levels were positively associated with plasma amyloid-ß 42 levels. While plasma NAbs-P2RY2-3 levels were negatively associated with brain amyloid burden in AD patients. CONCLUSION: These findings indicate an alteration of humoral immunity against P2RY2 in AD patients. Further mechanistical investigations are needed to reveal the role of NAbs-P2RY2 in the pathogenesis of AD.

Genetic Association Between NGFR, ADAM17 Gene Polymorphism, and Parkinson's Disease in the Chinese Han Population.

Parkinson's disease (PD) is a common neurodegenerative disease characterized by neuronal loss in the substantia nigra. The p75 neurotrophin receptor (p75NTR, encoded by NGFR) was found to play an important role in the selective neuronal death of dopamine neurons in the substantia nigra, as well as the pathogenesis and development of PD. To assess the association between NGFR gene polymorphism and the susceptibility of PD, this case-control study consisting of 414 PD patients and 623 age- and sex-matched controls in a Chinese Han cohort was conducted. Twelve tag-single nucleotide polymorphisms (tag-SNPs) were selected from the NGFR gene through the construction of linkage disequilibrium blocks. One tag-SNP from the ADAM17 gene was also selected owing to its function of encoding tumor necrosis factor α-converting enzyme, which is responsible for the shedding of the extracellular domain of p75NTR. A multiplex polymerase chain reaction-ligase detection reaction (PCR-LDR) method was applied for genotyping. The associations between tag-SNPs and the risk of PD with the adjustment for age and sex were analyzed by unconditional logistic regression, and five genetic models including codominant, dominant, recessive, over-dominant, and additive models were applied. The results showed that among the 13 tag-SNPs, rs741073 was associated with a reduced risk of PD in the codominant (OR = 0.71, 95% CI = 0.54-0.93, P = 0.037), dominant (OR = 0.76, 95% CI = 0.58-0.98, P = 0.033), and over-dominant models (OR = 0.71, 95% CI = 0.54-0.92, P = 0.010), and rs1804011 was also associated with a reduced risk of PD in the codominant (OR = 0.69, 95% CI = 0.50-0.95, P = 0.049), dominant (OR = 0.69, 95% CI = 0.50-0.93, P = 0.014), over-dominant (OR = 0.70, 95% CI = 0.51-0.96, P = 0.025), and additive models (OR = 0.72, 95% CI = 0.54-0.94, P = 0.016). However, these associations did not retain after Bonferroni correction. Conclusively, our study failed to reveal the association between the selected tag-SNPs within NGFR, ADAM17, and the susceptibility of PD. The role of p75NTR and its gene polymorphisms in the pathogenesis of PD needs to be further studied.