The Diagnostic Potential of Circulating Autoantibodies to Amyloid-ß in Alzheimer's Disease.

BACKGROUND: The profile of naturally occurring antibodies to amyloid-ß (NAbs-Aß) is altered in patients with Alzheimer's disease (AD). However, the diagnostic potential of NAbs-Aß for AD is not clear yet. OBJECTIVE: This study aims to investigate the diagnostic capacities of NAbs-Aß for AD. METHODS: A total of 40 AD patients and 40 cognitively normal (CN) controls were enrolled in this study. Levels of NAbs-Aß were detected by ELISA. The correlations of NAbs-Aß levels with cognitive function and AD-associated biomarkers were examined by Spearman correlation analysis. Diagnostic abilities of NAbs-Aß were evaluated by the receiver operating characteristic (ROC) curve analyses. The integrative diagnostic models were established by logistic regression models. RESULTS: We found that NAbs-Aß7-18 had the highest diagnostic capability (AUC = 0.72) among all single NAbs-Aß. The combined model (NAbs-Aß7-18, NAbs-Aß19-30, and NAbs-Aß25-36) had a noticeable improvement (AUC = 0.84) in the diagnostic capacity compared with each single NAbs-Aß. CONCLUSION: NAbs-Aßs are promising in the diagnosis of AD. Further investigations are needed to confirm the translational potential of this diagnostic strategy.

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.

Associations Between Plasma Klotho with Renal Function and Cerebrospinal Fluid Amyloid-ß Levels in Alzheimer's Disease: The Chongqing Ageing & Dementia Study.

BACKGROUND: The kidney-brain crosstalk has been involved in Alzheimer's disease (AD) with the mechanism remaining unclear. The anti-aging factor Klotho was reported to attenuate both kidney injury and AD pathologies. OBJECTIVE: To investigate whether plasma Klotho participated in kidney-brain crosstalk in AD. METHODS: We enrolled 33 PiB-PET-positive AD patients and 33 amyloid-ß (Aß)-negative age- and sex-matched cognitively normal (CN) controls from the Chongqing Ageing & Dementia Study (CADS). The levels of plasma Klotho, Aß, and tau in the cerebrospinal fluid (CSF) were measured by enzyme-linked immunosorbent assay. RESULTS: We found higher plasma Klotho and lower estimated glomerular filtration rate (eGFR) levels in AD patients compared with CN. The eGFR was positively associated with Aß42, Aß40 levels in CSF and negatively associated with CSF T-tau levels. Plasma Klotho levels were both negatively correlated with CSF Aß42 and eGFR. Mediation analysis showed that plasma Klotho mediated 24.96% of the association between eGFR and CSF Aß42. CONCLUSION: Renal function impacts brain Aß metabolism via the kidney-brain crosstalk, in which the plasma Klotho may be involved as a mediator. Targeting Klotho to regulate the kidney-brain crosstalk provides potential therapeutic approaches for AD.

Physiological clearance of Aß by spleen and splenectomy aggravates Alzheimer-type pathogenesis.

BACKGROUND: A previous study demonstrated that nearly 40%-60% of brain Aß flows out into the peripheral system for clearance. However, where and how circulating Aß is cleared in the periphery remains unclear. The spleen acts as a blood filter and an immune organ. The aim of the present study was to investigate the role of the spleen in the clearance of Aß in the periphery. METHODS: We investigated the physiological clearance of Aß by the spleen and established a mouse model of AD and spleen excision by removing the spleens of APP/PS1 mice to investigate the effect of splenectomy on AD mice. RESULTS: We found that Aß levels in the splenic artery were higher than those in the splenic vein, suggesting that circulating Aß is cleared when blood flows through the spleen. Next, we found that splenic monocytes/macrophages could take up Aß directly in vivo and in vitro. Splenectomy aggravated behaviour deficits, brain Aß burden and AD-related pathologies in AD mice. CONCLUSION: Our study reveals for the first time that the spleen exerts a physiological function of clearing circulating Aß in the periphery. Our study also suggests that splenectomy, which is a routine treatment for splenic rupture and hypersplenism, might accelerate the development of AD.

The Correlation of Tau Levels with Blood Monocyte Count in Patients with Alzheimer's Disease.

BACKGROUND: Recent studies have shown that monocytes can phagocytize the tau protein, which may ameliorate tau-type pathology in Alzheimer's disease (AD). However, there are few clinical studies on the relationship between monocytes and tau-type pathology in AD patients. OBJECTIVE: We aimed to explore changes in peripheral monocytes and their association with tau protein in AD patients. METHODS: A total of 127 clinically diagnosed AD patients and 100 age- and sex-matched cognitively normal controls were recruited for analysis of the correlation of plasma tau levels with the blood monocyte count. Cerebrospinal fluid (CSF) samples from 46 AD patients and 88 controls were further collected to analyze the correlation of CSF tau and amyloid-ß (Aß) levels with the blood monocyte count. 105 clinically diagnosed mild cognitive impairment (MCI) patients and 149 age- and sex-matched cognitively normal controls were recruited from another cohort for verification. RESULTS: Compared to normal controls, AD patients showed a significant reduction in the blood monocyte count. In addition, the monocyte count of AD patients was negatively correlated with CSF t-tau and p-tau levels but not with plasma tau levels. In normal people, monocyte count lack correlation with tau levels both in plasma and CSF. Monocyte count were not correlated with CSF Aß levels in either group but were negatively correlated with CSF tau/Aß42 levels in the AD group. We had further verified the correlations of monocyte count with CSF tau levels in another cohort. CONCLUSION: This study suggests that monocytes may play an important role in the clearance of tau protein in the brain.

Dynamic changes of CSF sPDGFRß during ageing and AD progression and associations with CSF ATN biomarkers.

BACKGROUND: Loss of brain capillary pericyte is involved in the pathologies and cognitive deficits in Alzheimer's disease (AD). The role of pericyte in early stage of AD pathogenesis remains unclear. METHODS: We investigated the dynamic changes of soluble platelet-derived growth factor receptor ß (sPDGFRß) in cerebrospinal fluid (CSF), a marker of brain pericyte injury, in transition from normal ageing to early AD in a cognitively unimpaired population aged 20 to 90 years. Association between sPDGFRß and ATN biomarkers were analyzed. RESULTS: In lifetime, CSF sPDGFRß continually increased since age of 20 years, followed by the increases of phosphorylated tau-181 (P-tau181) and total tau (T-tau) at the age of 22.2 years and 31.7 years, respectively; CSF Aß42 began to decline since the age of 39.6 years, indicating Aß deposition. The natural trajectories of biomarkers suggest that pericyte injury is an early event during transition from normal status to AD, even earlier than Aß deposition. In AD spectrum, CSF sPDGFRß was elevated in preclinical stage 2 and participants with suspected non-AD pathophysiologies. Additionally, CSF sPDGFRß was positively associated with P-tau181 and T-tau independently of Aß42, and significantly strengthened the effects of Aß42 on P-tau181, suggesting that pericyte injury accelerates Aß-mediated tau hyperphosphorylation. CONCLUSIONS: Our results suggest that pericyte injury contributes to AD progression in the early stage in an Aß-independent pathway. Recovery of pericyte function would be a target for prevention and early intervention of AD.

The association of serum uric acid with cognitive impairment and ATN biomarkers.

Background: Cognitive impairment (CI) has become a worldwide health problem. The relationship between CI and uric acid (UA) is contradictory. Objective: We included participants with a full spectrum of CI, from cognitively unimpaired (CU) to dementia, from the Chongqing Ageing & Dementia Study (CADS). Methods: First, we identified the relationships between serum UA (sUA) and cognitive function in different stages of CI. Second, we analyzed these relationships among different stages and types of CI. Finally, we explored the association between sUA and amyloid/tangle/neurodegeneration (ATN) biomarkers. Results: We recruited 427 participants from the CADS, including 382 participants with mini-mental state examination (MMSE) evaluation. The levels of sUA were positively correlated with MMSE scores (p < 0.001), and the correlation was prominent in the course of dementia and in the type of Alzheimer's disease (AD). The levels of UA had a positive correlation with plasma amyloid-ß 42 (Aß42) (p = 0.004). Higher levels of sUA weakened the correlation of MMSE scores with CSF ATN biomarkers and the correlation of CSF Aß42 with tau. Conclusion: UA is positively correlated with cognitive function, especially in the advanced stage of AD. The probable neuroprotective effects of sUA mainly act on Aß42 and the downstream pathological cascade.

Association of rs2072446 in the NGFR gene with the risk of Alzheimer's disease and amyloid-ß deposition in the brain.

INTRODUCTION AND AIMS: Alzheimer's disease (AD) is the most common form of dementia with a complex genetic background. The cause of sporadic AD (sAD) remains largely unknown. Increasing evidence shows that genetic variations play a crucial role in sAD. P75 neurotrophin receptor (p75NTR, encoded by NGFR) plays a critical role in the pathogenesis of AD. Yet, the relationship between NGFR gene polymorphisms and AD was less studied. This study aims to analyze the relationship of NGFR gene polymorphism with the risk of AD in the Chinese Han population and amyloid-ß deposition in the ADNI cohort. METHODS: This case-control association study was conducted in a Chinese Han cohort consisting of 366 sporadic AD (sAD) patients and 390 age- and sex-matched controls. Twelve tag-SNPs were selected and genotyped with a multiplex polymerase chain reaction-ligase detection reaction (PCR-LDR) method. The associations between tag-SNPs and the risk of AD were analyzed by logistic regression. Moreover, another cohort from the Alzheimer's Disease Neuroimaging Initiative (ADNI) database was included to examine the association of one tag-SNP (rs2072446) with indicators of amyloid deposition. Kaplan-Meier survival analysis and Cox proportional hazards models were used to test the predictive abilities of rs2072446 genotypes for AD progression. The mediation effects of Aß deposition on this association were subsequently tested by mediation analyses. RESULTS: After multiple testing corrections, one tag-SNP, rs2072446, was associated with an increased risk of sAD (additive model, OR = 1.79, Padjustment  = 0.0144). Analyses of the ADNI cohort showed that the minor allele (T) of rs2072446 was significantly associated with the heavier Aß burden, which further contributed to an increased risk of AD progression in APOE ε4 non-carrier. CONCLUSION: Our study found that rs2072446 in NGFR is associated with both the risk of sAD in the Chinese Han population and the amyloid burden in the ADNI cohort, which reveals the role of p75NTR in AD from a genetic perspective.

The Association of Serum Neurofilament Light Chain and Acute Ischaemic Stroke Is Influenced by Effective Revascularization.

Objective: To explore associations of serum neurofilament light chain (sNfL) at admission with clinical deficits and the long-term prognosis of acute ischaemic stroke (AIS). Methods: We recruited 110 AIS patients with serum sampled at hospital arrival. The concentrations of sNfL were detected by a Simoa HD-1 analyser. We first investigated the determinants of sNfL levels at admission within the study population. Associations of sNfL levels with National Institutes of Health Stroke Scale (NIHSS) scores and modified Rankin Scale (mRS) scores were then tested. We further divided the patients into revascularized and nonrevascularized groups, and the associations of sNfL levels with NIHSS and mRS scores were assessed in these subgroups. Results: Age, sex, stroke history, and the time between the onset of illness and arrival at the hospital were independent influencing factors of sNfL levels within the study population. The sNfL levels at admission were correlated with the NIHSS scores 7 days after stroke (p = 0.004) across all subjects but showed no correlation with the NIHSS scores at admission (p = 0.293) or the mRS scores 6 months after stroke (p = 0.065). Further analysis revealed that in the nonrevascularized group of AIS patients, the sNfL levels at admission were positively correlated with NIHSS scores (NIHSS at admission, p = 0.005; NIHSS 7 days after stroke, p = 0.003) and negatively correlated with mRS scores (p = 0.011). Conclusion: sNfL levels at admission could be a potential biomarker for predicting clinical deficits and prognosis in the natural course of AIS.

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.

The Correlations of Plasma Liver-Type Fatty Acid-Binding Protein with Amyloid-ß and Tau Levels in Patients with Alzheimer's Disease.

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-ß (Aß) 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 Aß and tau in CSF, were measured by enzyme-linked immunosorbent assay (ELISA). A single-molecule array (SIMOA) was used to detect plasma Aß 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/Aß42 (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 Aß42, Aß40, and t-tau, both FABP1/Aß42 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 Aß42 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.

Associations of plasma angiostatin and amyloid-ß and tau levels in Alzheimer's disease.

Angiostatin, an endogenous angiogenesis inhibitor generated by the proteolytic cleavage of plasminogen, was recently reported to contribute to the development of Alzheimer's disease (AD). However, whether there are pathological changes in angiostatin levels in individuals with AD dementia is unclear, and whether plasma angiostatin has a relationship with major AD pathological processes and cognitive impairment remains unknown. To examine plasma angiostatin levels in patients with AD dementia and investigate the associations of angiostatin with blood and cerebrospinal fluid (CSF) AD biomarkers, we conducted a cross-sectional study including 35 cognitively normal control (CN) subjects and 59 PiB-PET-positive AD dementia patients. We found that plasma angiostatin levels were decreased in AD dementia patients compared to CN subjects. Plasma angiostatin levels were negatively correlated with plasma Aß42 and Aß40 levels in AD dementia patients and positively correlated with CSF total tau (t-tau) levels and t-tau/Aß42 in AD dementia patients with APOE-ε4. In addition, plasma angiostatin levels had the potential to distinguish AD from CN. These findings suggest a link between angiostatin and AD pathogenesis and imply that angiostatin might be a potential diagnostic biomarker for AD.

Associations of plasma soluble CD22 levels with brain amyloid burden and cognitive decline in Alzheimer's disease.

CD22 has been suggested to contribute to Alzheimer's disease (AD) pathogenesis by inhibiting microglial amyloid ß (Aß) phagocytosis. Soluble CD22 (sCD22) generated by cleavage from cell membranes may be a marker of inflammation and microglial dysfunction; but alterations of sCD22 levels in AD and their correlation with AD biomarkers remain unclear. Plasma sCD22 levels were measured in cognitively normal non-AD participants and patients with preclinical AD and AD dementia from a Chinese cohort and the Australian Imaging, Biomarkers and Lifestyle Flagship Study of Ageing. Plasma sCD22 levels were elevated in patients with preclinical and dementia AD. Plasma sCD22 levels were negatively correlated with cerebrospinal fluid (CSF) Aß42 levels and Aß42/Aß40, and positively correlated with CSF phosphorylated tau levels and brain Aß burden, but negatively correlated with cognitive function. Moreover, higher plasma sCD22 levels were associated with faster cognitive decline during follow-up. These findings suggest that CD22 plays important roles in AD development, and that sCD22 is a potential biomarker for AD.

Spicy food consumption is associated with cognition and cerebrospinal fluid biomarkers of Alzheimer disease.

BACKGROUND: Recent studies suggest that a healthy diet helps to prevent the development of Alzheimer disease (AD). This study aimed to investigate whether spicy food consumption is associated with cognition and cerebrospinal fluid (CSF) biomarkers of AD in the Chinese population. METHODS: We enrolled 55 AD patients and 55 age- and gender-matched cognitively normal (CN) subjects in a case-control study, as well as a cohort of 131 participants without subjective cognitive decline (non-AD) in a cross-sectional study. Spicy food consumption was assessed using the Food Frequency Questionnaire (FFQ). Associations of FFQ scores with cognition and CSF biomarkers of AD were analyzed. RESULTS: In the case-control study, spicy food consumption was lower in AD patients than that in CNs (4.0 [4.0-8.0] vs. 8.0 [4.5-10.0], P < 0.001); FFQ scores were positively associated with Mini-Mental Status Examination scores in the total sample (r = 0.218, P = 0.014). In the cross-sectional study, the association between spicy food consumption and cognition levels was verified in non-AD subjects (r = 0.264, P = 0.0023). Moreover, higher FFQ scores were significantly associated with higher ß-Amyloid (1-42) (Aß42) levels and lower phospho-tau/Aß42 and total tau/Aß42 ratios in the CSF of non-AD subjects (P < 0.05). CONCLUSION: Spicy food consumption is closely related to higher cognition levels and reversed AD biomarkers in the CSF, suggesting that a capsaicin-rich diet might have the potential to modify the cognitive status and cerebral pathologies associated with AD.

Association of Polygenic Risk Score with Age at Onset and Cerebrospinal Fluid Biomarkers of Alzheimer's Disease in a Chinese Cohort.

To evaluate whether the polygenic profile modifies the development of sporadic Alzheimer's disease (sAD) and pathological biomarkers in cerebrospinal fluid (CSF), 462 sAD patients and 463 age-matched cognitively normal (CN) controls were genotyped for 35 single-nucleotide polymorphisms (SNPs) that are significantly associated with sAD. Then, the alleles found to be associated with sAD were used to build polygenic risk score (PRS) models to represent the genetic risk. Receiver operating characteristic (ROC) analyses and the Cox proportional hazards model were used to evaluate the predictive value of PRS for the sAD risk and age at onset. We measured the CSF levels of Aß42, Aß42/Aß40, total tau (T-tau), and phosphorylated tau (P-tau) in a subgroup (60 sAD and 200 CN participants), and analyzed their relationships with the PRSs. We found that 14 SNPs, including SNPs in the APOE, BIN1, CD33, EPHA1, SORL1, and TOMM40 genes, were associated with sAD risk in our cohort. The PRS models built with these SNPs showed potential for discriminating sAD patients from CN controls, and were able to predict the incidence rate of sAD and age at onset. Furthermore, the PRSs were correlated with the CSF levels of Aß42, Aß42/Aß40, T-tau, and P-tau. Our study suggests that PRS models hold promise for assessing the genetic risk and development of AD. As genetic risk profiles vary among populations, large-scale genome-wide sequencing studies are urgently needed to identify the genetic risk loci of sAD in Chinese populations to build accurate PRS models for clinical practice.

Plasma α-synuclein levels are increased in patients with obstructive sleep apnea syndrome.

OBJECTIVE: Obstructive sleep apnea syndrome (OSAS) is characterized by nocturnal intermittent hypoxemia and can increase the risk of Parkinson's disease. This study aimed to investigate the association between plasma α-synuclein levels and hypoxia in the patients with OSAS. METHODS: We recruited 42 OSAS patients and 46 controls with simple snoring matched for age and gender. OSAS was diagnosed on the basis of the clinical symptoms as well as the nighttime polysomnography. Plasma total α-synuclein and phosphorylated α-synuclein levels were measured by ELISA kits. RESULTS: The OSAS patients had significant higher levels of plasma total α-synuclein and phosphorylated α-synuclein levels. Both of the above indexes were positively correlated with the apnea-hypopnea index and the oxygen desaturation index, while they were negatively correlated with the mean and lowest oxyhemoglobin saturations. INTERPRETATION: This study suggests that chronic intermittent hypoxia can increase the α-synuclein levels, which may contribute to the pathogenesis of Parkinson's disease.

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.

Brain Amyloid-ß Deposition and Blood Biomarkers in Patients with Clinically Diagnosed Alzheimer's Disease.

Brain amyloid-ß (Aß) deposition is a hallmark to define Alzheimer's disease (AD). We investigated the positive rate of brain amyloid deposition assessed with 11C-Pittsburgh compound (PiB)-PET and blood Aß levels in a cohort of probable AD patients who were diagnosed according to the 1984 NINCDS-ADRDA criteria. Eighty-four subjects with a clinical diagnosis of probable AD dementia, amnestic mild cognitive impairment (MCI), and cognitively normal (CN) status were subjected to PiB-PET and 18F-fluorodeoxyglucose (FDG)-PET scans. Plasma biomarkers of Aß42, Aß40, and T-tau were measured using single molecule array technology. The positive rate of PiB-PET, the associations between PiB-PET status and FDG-PET, plasma biomarkers, and clinical manifestations were analyzed. PiB-PET was positive in 77.36% of probable AD patients, 31.80% of MCI patients, and 0 of NC. Plasma Aß42/Aß40 ratio was associated with PiB-PET, the ROC curve analysis revealing an AUC of 0.77 (95% CI: 0.66-0.87), with a sensitivity of 82% and specificity of 64%. Some clinical manifestations were associated with PiB-PET imaging. Our findings indicate that only three-fourths of patients diagnosed with probable AD fit the pathological criteria, suggesting that we should be cautious regarding the accuracy of AD diagnosis when no biomarker evidence is available in our clinical practice.

Cerebrospinal Fluid Amyloid-ß Levels are Increased in Patients with Insomnia.

Previous studies demonstrate that patients with sleep disorders are at risk of developing Alzheimer's disease (AD), with the mechanism unknown. It is suggested that acute sleep deprivation induces an increase of amyloid-ß (Aß), the major pathological agent in AD, in the cerebrospinal fluid (CSF). In the present study, we recruited 23 patients with chronic insomnia aged between 46 to 67 years and 23 healthy controls aged between 43 to 67 years. We investigated the CSF levels of Aß and tau, another pathological hallmark in the AD pathogenesis. We found that CSF Aß42 levels were significantly increased in insomnia patients. However, no significant difference was found in Aß40, total tau (t-Tau), and phosphorylated tau (p-Tau) between the two groups. Furthermore, we found that CSF Aß40 and Aß42 levels are significantly correlated with the sleep quality, as reflected by the Pittsburgh Sleep Quality Index (PSQI) scores. But no significant correlation was found in CSF t-Tau and p-Tau levels with PSQI. Our results indicate that chronic sleep disorders may induce the disruption of Aß metabolism in the brain, thus increase the risk for developing AD.