Serum Uric Acid May Aggravate Alzheimer’s Disease Risk by Affecting Amyloidosis in Cognitively Intact Older Adults: The CABLE Study

2021 ◽  
pp. 1-13
Author(s):  
Lin-Lin Li ◽  
Ya-Hui Ma ◽  
Yan-Lin Bi ◽  
Fu-Rong Sun ◽  
Hao Hu ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Uric Acid ◽  
Serum Uric Acid ◽  
Disease Risk ◽  
Sensitivity Analyses ◽  
Quadratic Model ◽  
Preclinical Ad ◽  
T Tau ◽  
Cognitively Intact

Background: Serum uric acid (SUA) affects the reaction of oxidative stress and free radicals in the neurodegenerative processes. However, whether SUA impacts Alzheimer’s disease (AD) pathology remains unclear. Objective: We aimed to explore whether high SUA levels can aggravate the neurobiological changes of AD in preclinical AD. Methods: We analyzed cognitively intact participants (n = 839, age 62.16 years) who received SUA and cerebrospinal fluid (CSF) biomarkers (amyloid-β [Aβ], total tau [t-Tau], and phosphorylated tau [p-Tau]) measurements from the Chinese Alzheimer’s Biomarker and LifestylE (CABLE) database using multivariable-adjusted linear models. Results: Levels of SUA in the preclinical AD elevated compared with the healthy controls (p = 0.007) and subjects with amyloid pathology had higher concentration of SUA than controls (p = 0.017). Roughly, equivalent levels of SUA displayed among cognitively intact individuals with or without tau pathology and neurodegeneration. CSF Aβ1 - 42 (p = 0.019) and Aβ1 - 42/Aβ1 - 40 (p = 0.027) were decreased and CSF p-Tau/Aβ1 - 42 (p = 0.009) and t-Tau/Aβ1 - 42 (p = 0.043) were increased with the highest (>  75th percentile) SUA when compared to lowest SUA, implying a high burden of cerebral amyloidosis in individuals with high SUA. Sensitivity analyses using the usual threshold to define hyperuricemia and precluding drug effects yielded robust associations. Nevertheless, the quadratic model did not show any U-shaped relationships between them. Conclusion: SUA may aggravate brain amyloid deposition in preclinical AD, which corroborated the detrimental role of SUA.

Social Networks and Cerebrospinal Fluid Biomarkers of Alzheimer’s Disease Pathology in Cognitively Intact Older Adults: The CABLE Study

2021 ◽  
pp. 1-10
Author(s):  
Ya-Hui Ma ◽  
Ya-Yu Wang ◽  
Lan Tan ◽  
Wei Xu ◽  
Xue-Ning Shen ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Social Networks ◽  
Cerebrospinal Fluid ◽  
Amyloid Β ◽  
Cognitive Status ◽  
Tau Proteins ◽  
Preclinical Ad ◽  
T Tau ◽  
Cognitively Intact

Background: Although social networks are deemed as moderators of incident Alzheimer’s disease (AD), few data are available on the mechanism relevant to AD pathology. Objective: We aimed to investigate whether social networks affect metabolism of cerebrospinal fluid (CSF) AD biomarkers during early stage and identify modification effects of genetic factor and subjective cognitive decline (SCD). Methods: We studied participants from the Chinese Alzheimer’s disease Biomarker and Lifestyle (CABLE) database who received cognition assessments and CSF amyloid-β (Aβ 1–42 and Aβ 1–40) and tau proteins (total-tau [T-tau] and phosphorylated-tau [P-tau]) measurements. The social networks were measured using self-reported questionnaires about social ties. Linear regression models were used. Results: Data were analyzed from 886 cognitively intact individuals aged 61.91 years (SD = 10.51), including 295 preclinical AD participants and 591 healthy controls. Social networks were mostly associated with CSF indicators of AD multi-pathologies (low P-tau/Aβ 1–42 and T-tau/Aβ 1–42 and high Aβ 1–42/Aβ 1–40). Significant differences of genetic and cognitive status were observed for CSF indicators, in which associations of social network scores with CSF P-tau and indicators of multi-pathologies appeared stronger in APOE 4 carriers (versus non-carriers) and participants with SCD (versus controls), respectively. Alternatively, more pronounced associations for CSF T-tau (β= –0.005, p <  0.001), Aβ 1–42/Aβ 1–40 (β= 0.481, p = 0.001), and T-tau/Aβ 1–42 (β= –0.047, p <  0.001) were noted in preclinical AD stage than controls. Conclusion: These findings consolidated strong links between social networks and AD risks. Social networks as a modifiable lifestyle probably affected metabolisms of multiple AD pathologies, especially among at-risk populations.

Inverse Association Between Serum Uric Acid Levels and Alzheimer’s Disease Risk

2015 ◽  
Vol 53 (4) ◽  
pp. 2594-2599 ◽  
Author(s):  
Na Du ◽  
Donghua Xu ◽  
Xu Hou ◽  
Xuejia Song ◽  
Cancan Liu ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Uric Acid ◽  
Serum Uric Acid ◽  
Disease Risk ◽  
Inverse Association

scholarly journals Association between methylation of BIN1 promoter in peripheral blood and preclinical Alzheimer’s disease

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Hao Hu ◽  
Lan Tan ◽  
Yan-Lin Bi ◽  
Wei Xu ◽  
Lin Tan ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Peripheral Blood ◽  
Late Onset ◽  
Early Stage ◽  
Susceptibility Gene ◽  
Subjective Cognitive Decline ◽  
Preclinical Ad ◽  
T Tau ◽  
New Evidence

AbstractThe bridging integrator 1 (BIN1) gene is the second most important susceptibility gene for late-onset Alzheimer’s disease (LOAD) after apolipoprotein E (APOE) gene. To explore whether the BIN1 methylation in peripheral blood changed in the early stage of LOAD, we included 814 participants (484 cognitively normal participants [CN] and 330 participants with subjective cognitive decline [SCD]) from the Chinese Alzheimer’s Biomarker and LifestylE (CABLE) database. Then we tested associations of methylation of BIN1 promoter in peripheral blood with the susceptibility for preclinical AD or early changes of cerebrospinal fluid (CSF) AD-related biomarkers. Results showed that SCD participants with significant AD biological characteristics had lower methylation levels of BIN1 promoter, even after correcting for covariates. Hypomethylation of BIN1 promoter were associated with decreased CSF Aβ42 (p = 0.0008), as well as increased p-tau/Aβ42 (p = 0.0001) and t-tau/Aβ42 (p < 0.0001) in total participants. Subgroup analysis showed that the above associations only remained in the SCD subgroup. In addition, hypomethylation of BIN1 promoter was also accompanied by increased CSF p-tau (p = 0.0028) and t-tau (p = 0.0130) in the SCD subgroup, which was independent of CSF Aβ42. Finally, above associations were still significant after correcting single nucleotide polymorphic sites (SNPs) and interaction of APOE ɛ4 status. Our study is the first to find a robust association between hypomethylation of BIN1 promoter in peripheral blood and preclinical AD. This provides new evidence for the involvement of BIN1 in AD, and may contribute to the discovery of new therapeutic targets for AD.

scholarly journals Diagnostic Blood Biomarkers in Alzheimer’s Disease

Biomedicines ◽  
2022 ◽  
Vol 10 (1) ◽  
pp. 169
Author(s):  
Jung Eun Park ◽  
Tamil Iniyan Gunasekaran ◽  
Yeong Hee Cho ◽  
Seong-Min Choi ◽  
Min-Kyung Song ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Early Diagnosis ◽  
Correlation Analysis ◽  
Disease Progression ◽  
Intracranial Volume ◽  
Strongly Correlated ◽  
Neurofilament Light Chain ◽  
Preclinical Ad ◽  
T Tau

Potential biomarkers for Alzheimer’s disease (AD) include amyloid β1–42 (Aβ1–42), t-Tau, p-Tau181, neurofilament light chain (NFL), and neuroimaging biomarkers. Their combined use is useful for diagnosing and monitoring the progress of AD. Therefore, further development of a combination of these biomarkers is essential. We investigated whether plasma NFL/Aβ1–42 can serve as a plasma-based primary screening biomarker reflecting brain neurodegeneration and amyloid pathology in AD for monitoring disease progression and early diagnosis. We measured the NFL and Aβ1–42 concentrations in the CSF and plasma samples and performed correlation analysis to evaluate the utility of these biomarkers in the early diagnosis and monitoring of AD spectrum disease progression. Pearson’s correlation analysis was used to analyse the associations between the fluid biomarkers and neuroimaging data. The study included 136 participants, classified into five groups: 28 cognitively normal individuals, 23 patients with preclinical AD, 22 amyloid-negative patients with amnestic mild cognitive impairment, 32 patients with prodromal AD, and 31 patients with AD dementia. With disease progression, the NFL concentrations increased and Aβ1–42 concentrations decreased. The plasma and CSF NFL/Aβ1–42 were strongly correlated (r = 0.558). Plasma NFL/Aβ1–42 was strongly correlated with hippocampal volume/intracranial volume (r = 0.409). In early AD, plasma NFL/Aβ1–42 was associated with higher diagnostic accuracy than the individual biomarkers. Moreover, in preclinical AD, plasma NFL/Aβ1–42 changed more rapidly than the CSF t-Tau or p-Tau181 concentrations. Our findings highlight the utility of plasma NFL/Aβ1–42 as a non-invasive plasma-based biomarker for early diagnosis and monitoring of AD spectrum disease progression.

scholarly journals The Influence of Serum Uric Acid Level on Alzheimer’s Disease: A Narrative Review

2021 ◽  
Vol 2021 ◽  
pp. 1-8
Author(s):  
Mengyuan Qiao ◽  
Chongli Chen ◽  
Yuqing Liang ◽  
Yuxi Luo ◽  
Wenbin Wu
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Uric Acid ◽  
Serum Uric Acid ◽  
Uric Acid Level ◽  
Acid Level ◽  
Serum Uric Acid Level ◽  
Strong Association ◽  
Antioxidant Properties ◽  
Special Cases

As a powerful antioxidant in the human body, uric acid (UA) has been the subject of increasing research that focused on its influence on Alzheimer’s disease (AD) in recent years. The latest literature was gathered to describe the influence of serum uric acid (SUA) level on the onset and progression of AD and to analyze the possibility that SUA is a biomarker of Alzheimer’s disease. A large number of existing studies suggested that the SUA level was lower or tended to decrease in patients with AD, and increased SUA level may have a protective effect in AD, which could reduce the risk of onset and slowing the course of the disease. However, some Mendelian randomization analyses suggested that genetically determined uric acid was not associated with AD risk. Existing research results are contradictory due to the high inconsistency of the studies, the selection of subjects, and other factors. UA also showed a strong association with cognitive function, and there appeared to be a gender-selective neuroprotective action. Due to its potent antioxidant properties, the low uric acid level may contribute to oxidative stress to accelerate disease progression. But some preclinical data showed a possibility that in some special cases, UA had a prooxidant properties. The possibility was raised in the discussion of the underlying mechanism that both the low uric acid level and the rapidly progressive course of the disease were the consequence of malnutrition. This paper reviews recent advances in the study of SUA and AD which offers the possibility of new biomarker, new prevention, and treatment strategies for Alzheimer’s disease.

Associations of Green Tea Consumption and Cerebrospinal Fluid Biomarkers of Alzheimer’s Disease Pathology in Cognitively Intact Older Adults: The CABLE Study

2020 ◽  
Vol 77 (1) ◽  
pp. 411-421
Author(s):  
Ya-Hui Ma ◽  
Jia-Huan Wu ◽  
Wei Xu ◽  
Xue-Ning Shen ◽  
Hui-Fu Wang ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cerebrospinal Fluid ◽  
Green Tea ◽  
Interaction Effects ◽  
Csf Biomarkers ◽  
Tea Consumption ◽  
And Gender ◽  
T Tau ◽  
Cognitively Intact

Background: Green tea has been widely recognized in ameliorating cognitive impairment and Alzheimer’s disease (AD), especially the progression of cognitive dysfunction. But the underlying mechanism is still unclear. Objective: This study was designed to determine the role of green tea consumption in the association with cerebrospinal fluid (CSF) biomarkers of AD pathology and to ascertain whether specific population backgrounds showed the differences toward these relationships. Methods: Multivariate linear models analyzed the available data on CSF biomarkers and frequency of green tea consumption of 722 cognitively intact participants from the Chinese Alzheimer’s Biomarker and LifestylE (CABLE) database, and we additionally detected the interaction effects of tea consumption with APOE ɛ4 status and gender using a two-way analysis of covariance. Results: Frequent green tea consumption was associated with a decreased level of CSF total-tau protein (t-tau) (p = 0.041) but not with the levels of CSF amyloid-β 42 (Aβ42) and CSF phosphorylated tau. The more pronounced associations of green tea consumption with CSF t-tau (p = 0.007) and CSF t-tau/Aβ42 (p = 0.039) were observed in individuals aged 65 years or younger. Additionally, males with frequent green tea consumption had a significantly low level of CSF t-tau/Aβ42 and a modest trend toward decreased CSF t-tau. There were no interaction effects of green tea consumption with APOE ɛ4 and gender. Conclusion: Collectively, our findings consolidated the favorable effects of green tea on the mitigation of AD risk. The constituents of green tea may improve abnormal tau metabolism and are promising targets in interventions and drug therapies.

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