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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.

The neurotrophin receptor p75 (p75NTR) plays important roles in regulating amyloid-beta (Aβ) metabolism in the brain. The expression of p75NTR is altered in the brain of patients with Alzheimer's disease (AD). In this study, we aimed to evaluate whether p75NTR mRNA level in the peripheral blood cells is changed among AD patients and its potential to be a biomarker for AD. The study subjects included 26 patients with AD (PiB-PET positive) and 28 cognitively normal controls (PiB-PET negative). RNA was extracted from peripheral blood cells of fast blood. p75NTR mRNA was measured using quantitative real-time PCR assay. p75NTR mRNA levels in blood cells were comparable between AD patients and controls. p75NTR mRNA levels in blood cells were not correlated with MMSE scores, ApoE genotypes, gender, and age. p75NTR mRNA expression in blood cells is not changed in AD patients and is unlikely to be a biomarker for AD.

Background: The dysregulation of lipid metabolism plays an important role in the pathogenesis of Alzheimer's disease (AD). Liver-type fatty acid-binding protein (L-FABP, also known as FABP1) is critical for fatty acid transport and may be involved in AD.Objective: To investigate whether the FABP1 level is altered in patients with AD, and its associations with levels of amyloid-β (Aβ) and tau in the plasma and cerebrospinal fluid (CSF).Methods: A cross-sectional study was conducted in a Chinese cohort consisting of 39 cognitively normal controls and 47 patients with AD. The levels of FABP1 in plasma, and Aβ and tau in CSF, were measured by enzyme-linked immunosorbent assay (ELISA). A single-molecule array (SIMOA) was used to detect plasma Aβ levels.Results: The level of plasma FABP1 was significantly elevated in the AD group (p = 0.0109). Further analysis showed a positive correlation of FABP1 with CSF total tau (t-tau) and phosphorylated tau (p-tau) levels. Besides, plasma FABP1/Aβ42 (AUC = 0.6794, p = 0.0071) and FABP1/t-tau (AUC = 0.7168, p = 0.0011) showed fair diagnostic efficacy for AD. When combined with other common AD biomarkers including plasma Aβ42, Aβ40, and t-tau, both FABP1/Aβ42 and FABP1/t-tau showed better diagnostic efficacy than using these biomarkers alone. Among all AUC analyses, the combination of plasma FABP1/t-tau and Aβ42 had the highest diagnostic value (AUC = 0.8075, p < 0.0001).Conclusion: These findings indicate that FABP1 may play a role in AD pathogenesis and be worthy of further investigation in the future. [ABSTRACT FROM AUTHOR]

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-β 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. [ABSTRACT FROM AUTHOR]