scholarly journals Altered Plasma Global Arginine Bioavailability Ratio in Early-stage Alzheimer’s Disease

2018 ◽  
Vol 8 (1) ◽  
pp. 34-41
Author(s):  
José M. Martínez-Martos ◽  
María E. Pulido-Navas ◽  
María J. Ramírez-Expósito
Keyword(s):  
Nitric Oxide ◽  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
High Performance ◽  
Early Stage ◽  
Bioactive Molecules ◽  
No Production ◽  
Arginine Metabolism ◽  
Roc Curve Analysis ◽  
Physiological Functions

Background: L-arginine is an amino acid that can be metabolized to form several bioactive molecules including Nitric Oxide (NO). In the Central Nervous System (CNS), NO regulates various and important physiological functions. However, the involvement of L-arginine metabolism –and by extension of NO- in Alzheimer’s disease (AD) pathogenesis, has been suggested. Objective: To determine the Global L-Arginine Bioavailability Ratio (GABR) and NO levels (as the sum of nitrates and nitrites, NOx) in the plasma of early-stage Alzheimer’s Disease (AD) patients in order to analyze if GABR can reflect an altered NO production, to confirm the importance of L-arginine metabolism in the development of the disease, and to evaluate the putative diagnostic/prognostic value of GABR. Method: GABR index is an indicator of the availability of L-arginine to form NO by nitric oxide synthases. It is calculated as the ratio between the levels of L-arginine and the sum of the levels of L-ornithine and L-citrulline. Plasma amino acids are measured by high-performance liquid chromatography coupled to fluorescence detection. Nitric oxide is measured in plasma as the sum of nitrates and nitrites (NOx). Results: No changes were found in L-arginine levels, whereas L-citrulline and L-ornithine levels were highly increased in AD patients. We also found that GABR decreased significantly by 47.8% in AD patients, whereas NOx levels increased significantly by 46.9%. Receiver Operator Characteristic (ROC) curve analysis for GABR showed a sensitivity of 78.1 and a specificity of 90.5. Conclusion: Low plasma GABR levels in AD patients reflect that the L-arginine-NO pathway has turned towards NO in AD, probably being related to the nitroxidative stress involved in neurodegenerative diseases. Furthermore, increased NOx could also be involved in several altered physiological functions. Therefore, GABR is proposed as a putative useful biomarker of the disease.

scholarly journals Utility of VSRAD for diagnosing Alzheimer’s disease in patients screened for dementia

2020 ◽  
Vol 48 (4) ◽  
pp. 030006052091727 ◽  
Author(s):  
Gaku Oshikubo ◽  
Akihisa Akahane ◽  
Aki Unno ◽  
Yukako Watanabe ◽  
Emi Ikebuchi ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Roc Curve ◽  
Early Stage ◽  
Regional Analysis ◽  
Mean Value ◽  
Cognitive Status ◽  
Roc Curve Analysis ◽  
Z Scores ◽  
The Mean

Objective To investigate the utility of the voxel-based specific regional analysis system for Alzheimer’s disease (VSRAD). Methods Clinical data from patients who underwent screening for dementia using VSRAD and the Japanese version of COGNISTAT, the Neurobehavioral Cognitive Status Examination, were retrospectively investigated to specify the domains of cognitive function that correlate with the statistical mean value of positive Z-scores in the target volume-of-interest (VOI). A receiver operating characteristic (ROC) curve was constructed to assess the mean value of positive Z-scores in discriminating patients with AD. Results A total of 72 patients were included (18 male and 54 female; 15 patients with AD). The mean value of positive Z-scores in the target VOI was significantly correlated with standardized COGNISTAT scores for Orientation and Memory in all patients (r = –0.35 and –0.38, respectively). ROC curve analysis revealed that a cut-off of 1.57 for mean value of positive Z-scores in the target VOI provided 69.4% accuracy in discriminating patients with AD, with a sensitivity of 0.80 and specificity of 0.67. Conclusions The results evinced the value of VSRAD in diagnosing AD. The degree of atrophy represented by the target VOI may reflect impairments in Orientation and Memory, which are early stage symptoms observed in AD.

scholarly journals Inducible nitric oxide synthase in tangle-bearing neurons of patients with Alzheimer's disease.

1996 ◽  
Vol 184 (4) ◽  
pp. 1425-1433 ◽  
Author(s):  
Y Vodovotz ◽  
M S Lucia ◽  
K C Flanders ◽  
L Chesler ◽  
Q W Xie ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Nitric Oxide Synthase ◽  
No Production ◽  
Tgf Beta ◽  
Control Subjects ◽  
Human Neurons ◽  
Oxide Synthase ◽  
High Output

In Alzheimer's disease (AD), affected neurons accumulate beta amyloid protein, components of which can induce mouse microglia to express the high-output isoform of nitric oxide synthase (NOS2) in vitro. Products of NOS2 can be neurotoxic. In mice, NOS2 is normally suppressed by transforming growth factor beta 1 (TGF-beta 1). Expression of TGF-beta 1 is decreased in brains from AD patients, a situation that might be permissive for accumulation of NOS2. Accordingly, we investigated the expression of NOS2 in patients with AD, using three monospecific antibodies: a previously described polyclonal and two new monoclonal antibodies. Neurofibrillary tangle-bearing neurons and neuropil threads contained NOS2 in brains from each of 11 AD patients ranging in age from 47 to 81 years. NOS2 was undetectable in brains from 6 control subjects aged 23-72 years, but was expressed in small amounts in 3 control subjects aged 77-87 years. Thus, human neurons can express NOS2 in vivo. The high-output pathway of NO production may contribute to pathogenesis in AD.

Cerebral blood flow regulation by nitric oxide in neurological disorders

2009 ◽  
Vol 87 (8) ◽  
pp. 581-594 ◽  
Author(s):  
Noboru Toda ◽  
Kazuhide Ayajiki ◽  
Tomio Okamura
Keyword(s):  
Nitric Oxide ◽  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Blood Flow ◽  
Cerebral Blood Flow ◽  
Cell Viability ◽  
No Production ◽  
Pathogenic Factors ◽  
The Central Nervous System ◽  
The Brain

There has been a rapid increase in the amount of information on the physiological and pathophysiological roles of nitric oxide (NO) in the brain. This molecule, which is formed by the constitutive isoforms of NO synthase, endothelial (eNOS) and neuronal (nNOS), plays an obligatory role in the regulation of cerebral blood flow and cell viability and in the protection of nerve cells or fibres against pathogenic factors associated with Alzheimer’s disease, Huntington’s disease, seizures, and migraine. Cerebral blood flow is impaired by decreased formation of NO from endothelial cells, autonomic nitrergic nerves, or brain neurons and also by increased production of reactive oxygen species (ROS). The NO–ROS interaction is an important topic in discussing blood flow and cell viability in the brain. Excessive production of NO by inducible NOS (iNOS) and nNOS in the brain participates in neurotoxicity. Recent studies on brain circulation have provided useful information about the involvement of impaired NO availability or uncontrolled NO production in cerebral pathogenesis, including Alzheimer’s disease, seizures, vascular headaches, and inflammatory disorders. Insight into the role of NO in the brain will contribute to our better understanding of cerebral hemodynamic dysfunction and will aid in developing novel therapeutic measures in diseases of the central nervous system.

Fluoxetine Protects against Dendritic Spine Loss in Middle-aged APPswe/PSEN1dE9 Double Transgenic Alzheimer’s Disease Mice

2020 ◽  
Vol 17 (1) ◽  
pp. 93-103 ◽  
Author(s):  
Jing Ma ◽  
Yuan Gao ◽  
Wei Tang ◽  
Wei Huang ◽  
Yong Tang
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Dendritic Spines ◽  
Dendritic Spine ◽  
Early Stage ◽  
Learning Ability ◽  
Middle Aged ◽  
Protein Levels ◽  
Spine Pathology ◽  
The Impact

Background: Studies have suggested that cognitive impairment in Alzheimer’s disease (AD) is associated with dendritic spine loss, especially in the hippocampus. Fluoxetine (FLX) has been shown to improve cognition in the early stage of AD and to be associated with diminishing synapse degeneration in the hippocampus. However, little is known about whether FLX affects the pathogenesis of AD in the middle-tolate stage and whether its effects are correlated with the amelioration of hippocampal dendritic dysfunction. Previously, it has been observed that FLX improves the spatial learning ability of middleaged APP/PS1 mice. Objective: In the present study, we further characterized the impact of FLX on dendritic spines in the hippocampus of middle-aged APP/PS1 mice. Results: It has been found that the numbers of dendritic spines in dentate gyrus (DG), CA1 and CA2/3 of hippocampus were significantly increased by FLX. Meanwhile, FLX effectively attenuated hyperphosphorylation of tau at Ser396 and elevated protein levels of postsynaptic density 95 (PSD-95) and synapsin-1 (SYN-1) in the hippocampus. Conclusion: These results indicated that the enhanced learning ability observed in FLX-treated middle-aged APP/PS1 mice might be associated with remarkable mitigation of hippocampal dendritic spine pathology by FLX and suggested that FLX might be explored as a new strategy for therapy of AD in the middle-to-late stage.

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 Plasma contact factors as novel biomarkers for diagnosing Alzheimer’s disease

2021 ◽  
Vol 9 (1) ◽  
Author(s):  
Jung Eun Park ◽  
Do Sung Lim ◽  
Yeong Hee Cho ◽  
Kyu Yeong Choi ◽  
Jang Jae Lee ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Early Stage ◽  
Clinical Stage ◽  
Area Under The Curve ◽  
Contact System ◽  
Plasma Diagnostic ◽  
Vascular Abnormalities ◽  
Prodromal Ad ◽  
Novel Biomarkers

Abstract Background Alzheimer’s disease (AD) is the most common cause of dementia and most of AD patients suffer from vascular abnormalities and neuroinflammation. There is an urgent need to develop novel blood biomarkers capable of diagnosing Alzheimer’s disease (AD) at very early stage. This study was performed to find out new accurate plasma diagnostic biomarkers for AD by investigating a direct relationship between plasma contact system and AD. Methods A total 101 of human CSF and plasma samples from normal and AD patients were analyzed. The contact factor activities in plasma were measured with the corresponding specific peptide substrates. Results The activities of contact factors (FXIIa, FXIa, plasma kallikrein) and FXa clearly increased and statistically correlated as AD progresses. We present here, for the first time, the FXIIa cut-off scores to as: > 26.3 U/ml for prodromal AD [area under the curve (AUC) = 0.783, p < 0.001] and > 27.2 U/ml for AD dementia (AUC = 0.906, p < 0.001). We also describe the cut-off scores from the ratios of CSF Aβ1–42 versus the contact factors. Of these, the representative ratio cut-off scores of Aβ1–42/FXIIa were to be: < 33.8 for prodromal AD (AUC = 0.965, p < 0.001) and < 27.44 for AD dementia (AUC = 1.0, p < 0.001). Conclusion The activation of plasma contact system is closely associated with clinical stage of AD, and FXIIa activity as well as the cut-off scores of CSF Aβ1–42/FXIIa can be used as novel accurate diagnostic AD biomarkers.

scholarly journals Early Detection of Alzheimer’s Disease Using Polar Harmonic Transforms and Optimized Wavelet Neural Network

2021 ◽  
Vol 11 (4) ◽  
pp. 1574
Author(s):  
Shabana Urooj ◽  
Satya P. Singh ◽  
Areej Malibari ◽  
Fadwa Alrowais ◽  
Shaeen Kalathil
Keyword(s):  
Neural Network ◽  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Early Detection ◽  
Differential Evolution ◽  
Early Stage ◽  
Selection Process ◽  
Parameter Tuning ◽  
Wavelet Neural Network ◽  
Tuning Parameter

Effective and accurate diagnosis of Alzheimer’s disease (AD), as well as early-stage detection, has gained more and more attention in recent years. For AD classification, we propose a new hybrid method for early detection of Alzheimer’s disease (AD) using Polar Harmonic Transforms (PHT) and Self-adaptive Differential Evolution Wavelet Neural Network (SaDE-WNN). The orthogonal moments are used for feature extraction from the grey matter tissues of structural Magnetic Resonance Imaging (MRI) data. Irrelevant features are removed by the feature selection process through evaluating the in-class and among-class variance. In recent years, WNNs have gained attention in classification tasks; however, they suffer from the problem of initial parameter tuning, parameter setting. We proposed a WNN with the self-adaptation technique for controlling the Differential Evolution (DE) parameters, i.e., the mutation scale factor (F) and the cross-over rate (CR). Experimental results on the Alzheimer’s disease Neuroimaging Initiative (ADNI) database indicate that the proposed method yields the best overall classification results between AD and mild cognitive impairment (MCI) (93.7% accuracy, 86.0% sensitivity, 98.0% specificity, and 0.97 area under the curve (AUC)), MCI and healthy control (HC) (92.9% accuracy, 95.2% sensitivity, 88.9% specificity, and 0.98 AUC), and AD and HC (94.4% accuracy, 88.7% sensitivity, 98.9% specificity and 0.99 AUC).

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