Authors: Gao, Ling | Jiang, Yu | Wei, Shan | Shang, Suhang | Li, Pei | Chen, Chen | Dang, Liangjun | Wang, Jin | Huo, Kang | Deng, Meiying | Wang, Jingyi | Zhang, Rong | Qu, Qiumin
Article Type: Research Article
Abstract: Background: Transport proteins, soluble low-density lipoprotein receptor-related protein-1 (sLRP1), and soluble receptor of advanced glycation end products (sRAGE), play an important role in the clearance of plasma amyloid-β (Aβ). However, their relationship is not clear. Objective: The aim was to explore the relationship between plasma levels of sLRP1, sRAGE, and Aβ in a cross-sectional study. Methods: A total of 1,185 cognitively normal participants (age above 40) from a village in the suburbs of Xi’an, China were enrolled from October 8, 2014 to March 30, 2015. Plasma Aβ40 , Aβ42 , sLRP1, and sRAGE were tested using a commercial ELISA. Apolipoprotein …E (APOE ) genotyping was conducted using PCR and sequencing. The relationship between plasma levels of sLRP1, sRAGE, and Aβ was analyzed using Pearson’s correlation analysis and multiple linear regression. Results: In the total population, Log sLRP1 and Log sRAGE were positively correlated with plasma Aβ40 (r = 0.103, p < 0.001; r = 0.064, p = 0.027, respectively), but neither were associated with plasma Aβ42 . After multivariable adjustment in the regression model, Log sLRP1 and Log sRAGE were still positively related with plasma Aβ40 (β= 2.969, p < 0.001; β= 1.936, p = 0.017, respectively) but not Aβ42 . Furthermore, the positive correlations between transport proteins and plasma Aβ40 remained significant only in APOE ɛ 4 non-carriers after Pearson’s analysis and multiple regression analysis after stratification by gene status. Conclusion: The concentrations of plasma sLRP1 and sRAGE had a significant impact on the level of plasma Aβ40 in cognitively normal adults, especially in APOE ɛ 4 non-carriers. However, the mechanism by which the transport proteins are involved in peripheral Aβ clearance and the relationship between transporters and amyloid burden in the brain needs further validation. Show more
Keywords: Alzheimer’s disease, amyloid-β, soluble low-density lipoprotein receptor-related protein-1 (sLRP1), soluble receptor of advanced glycation end products (sRAGE), transport proteins
DOI: 10.3233/JAD-180399
Citation: Journal of Alzheimer's Disease, vol. 65, no. 3, pp. 951-961, 2018
Authors: Liu, Peng | Zhao, Beiyu | Wei, Meng | Li, Yanbo | Liu, Jie | Ma, Louyan | Shang, Suhang | Huo, Kang | Wang, Jin | Li, Rui | Qu, Qiumin
Article Type: Research Article
Abstract: Alzheimer’s disease (AD) is the most common age-associated neurodegenerative disease featured by progressive learning and memory deficit, and Aβ was identified as playing a key role in the process of AD and was theorized to be caused by the imbalance of production and clearance. Increasing evidence suggested an association between sleep deprivation and AD. Our recent study found that chronic sleep restriction (CSR) caused cognitive impairment and Aβ accumulation in rats, but the underlining mechanism was unclear. In the present study, we investigated the effects of inflammation on Aβ accumulation induced by CSR. We found that CSR significantly increased the …expression of interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α ), inducible nitric oxide synthase (iNOS), and nitric oxide (NO) in brain, and the inflammatory factors levels were positively correlated with Aβ42 deposition. Additionally, the inflammatory factors were correlated with BACE1, LRP-1, and RAGE levels in both the hippocampus and the prefrontal cortex. Furthermore, the plasma levels of IL-1β, TNF-α , and NO were elevated after CSR, and the concentration of plasma inflammatory mediators were correlated with plasma levels of sLRP1 and sRAGE. These results suggested that the inflammation in brain and plasma might be involved in the CSR-induced Aβ accumulation. Show more
Keywords: Alzheimer’s disease, amyloid-β, chronic sleep restriction, inflammation, risk factor
DOI: 10.3233/JAD-191317
Citation: Journal of Alzheimer's Disease, vol. 74, no. 3, pp. 759-773, 2020
Authors: Wang, Jin | Qiao, Fan | Shang, Suhang | Li, Pei | Chen, Chen | Dang, Liangjun | Jiang, Yu | Huo, Kang | Deng, Meiying | Wang, Jingyi | Qu, Qiumin
Article Type: Research Article
Abstract: Background: Aggregation and deposition of amyloid-β (Aβ) in the brain is the main pathological change of Alzheimer’s disease (AD). Decreased Aβ42 in the cerebrospinal fluid has been confirmed as a biomarker of AD; however, the relationship between plasma Aβ and cognitive impairment is currently unclear. Objective: The aim was to explore the relationship between plasma Aβ and cognitive impairment in a cross-sectional study. Methods: A total of 1,314 subjects (age above 40) from a village in the suburbs of Xi’an, China were enrolled between October 8, 2014 and March 30, 2015. A validated Chinese version of the Mini-Mental State Examination …and neuropsychological battery were used to assess cognition. Levels of plasma Aβ42 and Aβ40 were tested using commercial enzyme-linked immunosorbent assay. Relationship of plasma Aβ and cognitive impairment was analyzed using logistic regression analysis. Results: Of the enrolled subjects, 1,180 (89.80%) had normal cognition, 85 (6.47%) had possible cognitive impairment and 49 (3.73%) had probable cognitive impairment. Logistic regression analysis showed that the Aβ42 /Aβ40 ratio (OR = 4.042, 95% CI: 1.248–11.098, p = 0.012) and plasma Aβ42 (OR = 1.036, 95% CI: 1.003–1.071, p = 0.031) was higher in the possible cognitive impairment than that in the normal cognition group. Furthermore, the plasma Aβ42 /Aβ40 ratio was higher in the possible cognitive impairment group than that in the probable cognitive impairment group (OR = 0.029, 95% CI: 0.002–0.450, p = 0.011). Conclusions: Levels of plasma Aβ42 and Aβ42 /Aβ40 ratio were elevated in patients with possible cognitive impairment, indicating that plasma Aβ42 and Aβ42 /Aβ40 ratio increases may be more pronounced in early stage of cognitive impairment. Show more
Keywords: Alzheimer’s disease, amyloid-β, cognitive impairment, plasma
DOI: 10.3233/JAD-180140
Citation: Journal of Alzheimer's Disease, vol. 64, no. 1, pp. 61-69, 2018
Authors: Gao, Ling | Wang, Jin | Jiang, Yu | Wei, Shan | Shang, Suhang | Chen, Chen | Dang, Liangjun | Huo, Kang | Deng, Meiying | Wang, Jingyi | Qu, Qiumin
Article Type: Research Article
Abstract: Background: Transport proteins, soluble LRP1 (sLRP1) and soluble RAGE (sRAGE), play a pivotal role in the peripheral clearance of plasma amyloid-β (Aβ). However, their relationship is seldom discussed, especially in Alzheimer’s disease (AD). Objective: To explore whether their relationship in patients with AD varied from those in cognitively normal (CN) controls. Methods: We initially recruited 70 patients with AD and 725 CN controls, then applied propensity score matching (PSM) analysis to balance the differences between two groups. Plasma levels of sLRP1, sRAGE, and Aβ were measured using commercial ELISA kits and log transformed when skewed distributed. The relationship between sLRP1/sRAGE …and plasma Aβ were analyzed using Pearson’s correlation analysis followed by multiple linear regression separately in the original population and matched participants. Results: After PSM, 70 patients with AD and 140 matched controls were included for further analysis. Log sLRP1 was positively correlated with plasma Aβ40 in matched CN controls (r = 0.222, p = 0.008) but not in patients with AD (r = 0.137, p = 0.260). After multivariable adjustment, Log sLRP1 remained significantly associated with plasma Aβ40 in the CN group (β= 7.347, p = 0.014) but not in the AD group (β= 10.409, p = 0.105). In contrast, Log sLRP1 was not correlated with plasma Aβ42 in patients with AD or CN controls, and Log sRAGE was consistently not associated with plasma Aβ40 or Aβ42 in either group. Conclusion: The significant correlation between sLRP1 and plasma Aβ40 present in CN controls was not found in patients with AD, suggesting that their relationship was different in AD. However, the specific mechanisms and its influence on cerebral amyloid burden require further validation. Show more
Keywords: Alzheimer’s disease, plasma amyloid-β, propensity score matching, soluble low-density lipoprotein receptor-related protein-1, soluble receptor of advanced glycation end products
DOI: 10.3233/JAD-191320
Citation: Journal of Alzheimer's Disease, vol. 78, no. 2, pp. 699-709, 2020
Authors: Gao, Ling | Dang, Liangjun | Wei, Shan | Hu, Ningwei | Gao, Fan | Peng, Wei | Shang, Suhang | Zhao, Yi | Chen, Chen | Guo, Xiaojuan | Huo, Kang | Wang, Jingyi | Wang, Jin | Qu, Qiumin
Article Type: Research Article
Abstract: Background: Soluble low-density lipoprotein receptor-related protein-1 (sLRP1) and soluble receptor of advanced glycation end products (sRAGE) play major roles in peripheral clearance of amyloid-β (Aβ). Objective: To determine the relationship between baseline sLRP1/sRAGE and early cognitive decline in a longitudinal study and explore the possible effect of apolipoprotein E (APOE ) on their association. Methods: Cognitively normal subjects were followed-up for 4 years. The baseline plasma levels of sLRP1 and sRAGE were measured using commercial ELISA kits. Global cognition was evaluated by Mini-Mental State Examination (MMSE), and cognitive decline was defined as a ≥2-point decrease of MMSE after 4 years. …The association between baseline sLRP1/sRAGE and 4-year cognitive decline were analyzed using logistic regression analysis. Interaction analysis was performed to discover the potential effect of APOE genotype on the relationship. Results: 769 participants were included in the final analysis, with 122 subjects (15.86%) were cognitive decline. Baseline sLRP1/sRAGE levels were not associated with 4-year cognitive decline after multivariable adjustments in the total cohort. However, there was significant interaction effect between sRAGE and APOE genotype on cognitive decline (adjusted odds ratio [OR] = 2.09, 95% confidence interval [CI]: 1.13–3.86, p = 0.019). Lower levels of sRAGE were associated with increased risk of cognitive decline among APOE ɛ4 non-carriers (adjusted OR = 1.60, 95% CI: 1.04–2.48, p = 0.034). Conclusion: Individuals with lower levels of sRAGE had an increased risk of 4-year cognitive decline in APOE ɛ4 non-carriers, indicating that the association between sRAGE and cognitive decline might depend on the APOE genotype. However, the specific mechanisms need to be further elucidated. Show more
Keywords: Alzheimer’s disease, apolipoprotein E, cognitive impairment, longitudinal study, plasma amyloid-β transporters
DOI: 10.3233/JAD-215228
Citation: Journal of Alzheimer's Disease, vol. 86, no. 2, pp. 801-812, 2022
Authors: Wei, Shan | Shang, Suhang | Dang, Liangjun | Gao, Fan | Gao, Yao | Gao, Ling | Chen, Chen | Huo, Kang | Wang, Jingyi | Wang, Jin | Qu, Qiumin
Article Type: Research Article
Abstract: Background: Studies have found that blood lipids are associated with plasma amyloid-β (Aβ) levels, but the underlying mechanism is still unclear. Two Aβ transporters, soluble form of low-density lipoprotein receptor related protein-1 (sLRP1) and soluble receptor of advanced glycation end products (sRAGE), are crucial in peripheral Aβ transport. Objective: The aim was to investigate the effects of lipids on the relationships between plasma Aβ and transporter levels. Methods: This study included 1,436 adults aged 40 to 88 years old. Blood Aβ, sLRP1, sRAGE, and lipid levels were measured. Univariate and multivariate analyses were used to analyze the relationships between lipids …and plasma Aβ, sLRP1, and sRAGE. Results: After adjusting for all possible covariates, high-density lipoprotein (HDL-c) was positively associated with plasma Aβ42 and sRAGE (β= 6.158, p = 0.049; β= 121.156, p < 0.001, respectively), while triglyceride (TG) was negatively associated with plasma Aβ40 , Aβ42 , and sRAGE (β= –48.389, p = 0.017; β= –11.142, p = 0.020; β= –147.937, p = 0.003, respectively). Additionally, positive correlations were found between plasma Aβ and sRAGE in the normal TG (Aβ40 : β= 0.034, p = 0.005; Aβ42 : β= 0.010, p = 0.001) and HDL-c groups (Aβ40 : β= 0.023, p = 0.033; Aβ42 : β= 0.008, p = 0.002) but not in the high TG and low HDL-c groups. Conclusion: Abnormal levels of TG and HDL-c are associated with decreased Aβ and sRAGE levels. Positive correlations between plasma Aβ and sRAGE were only found in the normal TG and HDL-c groups but not in the high TG and low HDL-c groups. These results indicated that dyslipidemia contributing to plasma Aβ levels might also be involved in peripheral Aβ clearance. Show more
Keywords: Alzheimer’s disease, amyloid-β, high-density lipoprotein, soluble low-density lipoprotein receptor-related protein-1, soluble receptor of advanced glycation end products, triglyceride
DOI: 10.3233/JAD-210405
Citation: Journal of Alzheimer's Disease, vol. 84, no. 1, pp. 303-314, 2021
Authors: Wei, Meng | Zhao, Beiyu | Huo, Kang | Deng, Yongning | Shang, Suhang | Liu, Jie | Li, Yanbo | Ma, Louyan | Jiang, Yu | Dang, Liangjun | Chen, Chen | Wei, Shan | Zhang, Juanli | Yang, Hailei | Gao, Fan | Qu, Qiumin
Article Type: Research Article
Abstract: Background: Sleep is an important physiological process and beneficial in the removal of brain metabolites and functional recovery. Prior studies have shown that sleep disorders are significant risk factors for Alzheimer’s disease (AD). Objective: The present study was designed to characterize the effect of short-term total sleep deprivation (TSD) on plasma amyloid-β (Aβ) concentrations. Methods: A clinical trial was conducted between March 1, 2016, and April 1, 2016. Twenty volunteers (age 27.3±3.4 years) with normal cognitive function and sleeping habits were recruited from the local population. Participants underwent 24 h of TSD. Periprocedural blood samples were collected to compare the changes …of plasma Aβ42 , Aβ40 , low-density lipoprotein receptor-related protein (sLRP-1), soluble receptors for advanced glycation end products (sRAGE), and serum superoxide dismutase (SOD) and malonaldehyde (MDA). Results: TSD increased morning plasma Aβ40 levels by 32.6% (p < 0.001) and decreased the Aβ42 /Aβ40 ratio by 19.3% (p < 0.001). A positive relationship was found between TSD duration and plasma Aβ40 level (r = 0.51, p < 0.001) and Aβ40 /Aβ42 ratio (r = 0.25, p = 0.003). Plasma concentrations of sLRP1 (p = 0.018) and sRAGE (p = 0.001) decreased significantly after TSD. Aβ40 and Aβ42 plasma concentrations correlated with plasma levels of sLRP1 and sRAGE. Serum SOD decreased after TSD (p = 0.005), whereas serum MDA was increased (p = 0.001). Conclusion: Sleep deprivation can lead to an elevation of plasma Aβ40 and decrease of the Aβ42 /Aβ40 ratio. The underlying mechanisms may be related to increased oxidative stress and impaired peripheral Aβ clearance as pathomechanisms of AD. Show more
Keywords: Alzheimer’s disease, amyloid-β, sleep, sleep deprivation
DOI: 10.3233/JAD-161213
Citation: Journal of Alzheimer's Disease, vol. 57, no. 3, pp. 899-906, 2017