scholarly journals Cerebral Responses to Acupuncture at GV24 and Bilateral GB13 in Rat Models of Alzheimer’s Disease

2018 ◽  
Vol 2018 ◽  
pp. 1-10 ◽  
Author(s):  
Shaoyang Cui ◽  
Mingzhu Xu ◽  
Jianting Huang ◽  
Qing Mei Wang ◽  
Xinsheng Lai ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Neurological Diseases ◽  
Statistical Parametric Mapping ◽  
Insular Cortex ◽  
Retrosplenial Cortex ◽  
Association Cortex ◽  
Control Group ◽  
Cerebral Peduncle ◽  
Positron Emission

Acupuncture has been widely used in China to treat neurological diseases including Alzheimer’s disease (AD). However, its mechanism remains unclear. In the present study, eighty healthy Wistar rats were divided into a normal control group (n=15) and premodel group (n=65). Forty-five rats that met the criteria for the AD model were then randomly divided into the model group (MG), the nonacupoint group (NG), and the acupoint group (AG). All rats received positron emission tomography (PET) scanning, and the images were analyzed with Statistical Parametric Mapping 8.0. MG exhibited hypometabolism in the olfactory bulb, insular cortex, orbital cortex, prelimbic cortex, striatum, parietal association cortex, visual cortex, cingulate gyrus, and retrosplenial cortex. AG exhibited prominent and extensive hypermetabolism in the thalamus, hypothalamus, bed nucleus of the stria terminalis, cerebral peduncle, midbrain tegmentum, and pontine tegmentum compared to NG. These results demonstrated that acupuncturing at GV24 and bilateral GB13 acupoints may improve the learning and memory abilities of the AD rats, probably via altering cerebral glucose metabolism (CGM) in the hypothalamus, thalamus, and brain stem. The observed effects of acupuncture may be caused by regulating the distribution of certain kinds of neurotransmitters and enhancing synaptic plasticity.

The Precuneus – A Witness for Excessive Aβ Gathering in Alzheimer’s Disease Pathology

2018 ◽  
Vol 18 (5-6) ◽  
pp. 302-309 ◽  
Author(s):  
Gayane Aghakhanyan ◽  
Andrea Vergallo ◽  
Marta Gennaro ◽  
Sara Mazzarri ◽  
Federica Guidoccio ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Disease Duration ◽  
Standardized Uptake Value ◽  
Positive Association ◽  
Analysis Of Covariance ◽  
Qualitative Assessment ◽  
Control Group ◽  
Positron Emission

Evidence of cortical beta-amyloid (Aβ) load, assessed by Aβ positron emission tomography (Aβ-PET), is an established in vivo biomarker of Alzheimer’s disease (AD)-related pathophysiology. Qualitative assessment of Aβ-PET provides binary information; meanwhile semiquantitative approaches require a parcellation of PET image either manually or by placement of atlas-based volumes of interest. We supposed that a whole-brain approach with voxel-by-voxel standardized uptake value ratio (SUVr) parametric images may better elucidate the spatial trajectories of Aβ burden along the continuum of AD. Methods: We recruited 32 subjects with a diagnosis of probable AD dementia (ADD, n = 20) and mild cognitive impairment due to AD (MCI-AD, n = 12) according to the NIA-AA 2011 criteria. We also enrolled a control group of 6 cognitively healthy individuals (HCs) with preserved cognitive functions and negative Aβ-PET scan. The PET images were spatially normalized using the AV45 PET template in the MNI brain space. Subsequently, parametric SUVr images were calculated using the whole cerebellum as a reference region. A voxel-wise analysis of covariance was used to compare (between groups) the Αβ distribution pattern considering age as a nuisance covariate. Results: Both ADD and MCI-AD subjects showed a widespread increase in radiotracer uptake when compared with HC participants (p < 0.001, uncorrected). After applying a multiple comparison correction (p < 0.05, corrected), a relative large cluster of increased [18F]-flor­betapir uptake was observed in the precuneus in the ADD and MCI-AD groups compared to HCs. Voxel-wise regression analysis showed a significant positive linear association between the voxel-wise SUVr values and the disease duration. Conclusions: The voxel-wise semiquantitative analysis shows that the precuneus is a region with higher vulnerability to Aβ depositions when compared to other cortical regions in both MCI-AD and ADD subjects. We think that the precuneus is a promising PET-based outcome measure for clinical trials of drugs targeting brain Aβ. We found a positive association between the overall Aβ-PET SUVr and the disease duration suggesting that the region-specific slow saturation of Aβ deposition continuously takes place as the disease progresses.

scholarly journals Machine Learning Driven Profiling of Cerebrospinal Fluid Core Biomarkers in Alzheimer’s Disease and Other Neurological Disorders

2021 ◽  
Vol 15 ◽  
Author(s):  
Giovanni Bellomo ◽  
Antonio Indaco ◽  
Davide Chiasserini ◽  
Emanuela Maderna ◽  
Federico Paolini Paoletti ◽  
...  
Keyword(s):  
Machine Learning ◽  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Neurological Disorders ◽  
Large Scale ◽  
Clustering Algorithm ◽  
Neurological Diseases ◽  
Gaussian Mixture ◽  
Control Group ◽  
T Tau

Amyloid-beta (Aβ) 42/40 ratio, tau phosphorylated at threonine-181 (p-tau), and total-tau (t-tau) are considered core biomarkers for the diagnosis of Alzheimer’s disease (AD). The use of fully automated biomarker assays has been shown to reduce the intra- and inter-laboratory variability, which is a critical factor when defining cut-off values. The calculation of cut-off values is often influenced by the composition of AD and control groups. Indeed, the clinically defined AD group may include patients affected by other forms of dementia, while the control group is often very heterogeneous due to the inclusion of subjects diagnosed with other neurological diseases (OND). In this context, unsupervised machine learning approaches may overcome these issues providing unbiased cut-off values and data-driven patient stratification according to the sole distribution of biomarkers. In this work, we took advantage of the reproducibility of automated determination of the CSF core AD biomarkers to compare two large cohorts of patients diagnosed with different neurological disorders and enrolled in two centers with established expertise in AD biomarkers. We applied an unsupervised Gaussian mixture model clustering algorithm and found that our large series of patients could be classified in six clusters according to their CSF biomarker profile, some presenting a typical AD-like profile and some a non-AD profile. By considering the frequencies of clinically defined OND and AD subjects in clusters, we subsequently computed cluster-based cut-off values for Aβ42/Aβ40, p-tau, and t-tau. This approach promises to be useful for large-scale biomarker studies aimed at providing efficient biochemical phenotyping of neurological diseases.

scholarly journals Targeted Neurotransmitters Profiling Identifies Metabolic Signatures in Rat Brain by LC-MS/MS: Application in Insomnia, Depression and Alzheimer’s Disease

Molecules ◽  
2018 ◽  
Vol 23 (9) ◽  
pp. 2375 ◽  
Author(s):  
Huarong Xu ◽  
Zhenru Wang ◽  
Lin Zhu ◽  
Zhenyu Sui ◽  
Wenchuan Bi ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Nervous System ◽  
Rat Brain ◽  
Neurological Diseases ◽  
Control Group ◽  
Cross Sectional ◽  
Linear Discriminant ◽  
Symptom Complex ◽  
Brain Tissues

Epidemiological, cross-sectional, and prospective studies have suggested that insomnia, Alzheimer’s disease (AD) and depression are mutually interacting conditions and frequently co-occur. The monoamine and amino acid neurotransmitter systems in central nervous system were involved in the examination of neurobiological processes of this symptom complex. However, few studies have reported systematic and contrastive discussion of different neurotransmitters (NTs) changing in these neurological diseases. Thus, it is necessary to establish a reliable analytical method to monitoring NTs and their metabolite levels in rat brain tissues for elucidating the differences in pathophysiology of these neurological diseases. A rapid, sensitive and reliable LC-MS/MS method was established for simultaneous determination of the NTs and their metabolites, including tryptophan (Trp), tyrosine (Tyr), serotonin (5-HT), 5-hydroxyindolacetic acid (5-HIAA), dopamine (DA), acetylcholine (ACh), norepinephrine (NE), glutamic acid (Glu), and γ-aminobutyric acid (GABA) in rat brain tissues. The mobile phase consisting of methanol and 0.01% formic acid in water was performed on an Inertsil EP C18 column, and the developed method was validated well. Results demonstrated that there were significant differences for 5-HT, DA, NE, Trp, Tyr and ACh between model and control group in all three models, and a Bayes linear discriminant function was established to distinguish these three kinds of nervous system diseases by DA, Tyr and ACh for their significant differences among control and three model groups. It could be an excellent strategy to provide perceptions into the similarity and differentia of mechanisms from the point of NTs’ changing in brain directly and a new method to distinguish insomnia, depression and AD from view of essence.

Alzheimer’s Disease Targeted Nano-Based Drug Delivery Systems

2020 ◽  
Vol 21 (7) ◽  
pp. 628-646
Author(s):  
Gülcem Altinoglu ◽  
Terin Adali
Keyword(s):  
Alzheimer’S Disease ◽  
Drug Delivery ◽  
Alzheimer's Disease ◽  
Neurological Diseases ◽  
Sustained Drug Release ◽  
Physiochemical Properties ◽  
Conventional Drug ◽  
Health Care Burden ◽  
The Central Nervous System ◽  
Effective Drugs

Alzheimer’s disease (AD) is the most common neurodegenerative disease, and is part of a massive and growing health care burden that is destroying the cognitive function of more than 50 million individuals worldwide. Today, therapeutic options are limited to approaches with mild symptomatic benefits. The failure in developing effective drugs is attributed to, but not limited to the highly heterogeneous nature of AD with multiple underlying hypotheses and multifactorial pathology. In addition, targeted drug delivery to the central nervous system (CNS), for the diagnosis and therapy of neurological diseases like AD, is restricted by the challenges posed by blood-brain interfaces surrounding the CNS, limiting the bioavailability of therapeutics. Research done over the last decade has focused on developing new strategies to overcome these limitations and successfully deliver drugs to the CNS. Nanoparticles, that are capable of encapsulating drugs with sustained drug release profiles and adjustable physiochemical properties, can cross the protective barriers surrounding the CNS. Thus, nanotechnology offers new hope for AD treatment as a strong alternative to conventional drug delivery mechanisms. In this review, the potential application of nanoparticle based approaches in Alzheimer’s disease and their implications in therapy is discussed.

Alzheimer’s Disease: Erythrocyte 2,3-diphosphoglycerate Content and Circulating Erythropoietin

2019 ◽  
Vol 16 (9) ◽  
pp. 834-835
Author(s):  
Petter Järemo ◽  
Alenka Jejcic ◽  
Vesna Jelic ◽  
Tasmin Shahnaz ◽  
Homira Behbahani ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cognitive Impairment ◽  
Cell Damage ◽  
Control Group ◽  
Red Cell ◽  
Oxygen Release ◽  
Regulatory Pathways ◽  
Β Amyloid ◽  
2,3 Dpg

Background: Alzheimer’s Disease (AD) features the accumulation of β-amyloid in erythrocytes. The subsequent red cell damage may well affect their oxygen-carrying capabilities. 2,3- diphosphoglycerate (2,3-DPG) binds to the hemoglobin thereby promoting oxygen release. It is theorized that 2,3-DPG is reduced in AD and that the resulting hypoxia triggers erythropoietin (EPO) release. Methods & Objective: To explore this theory, we analyzed red cell 2,3-DPG content and EPO in AD, mild cognitive impairment, and the control group, subjective cognitive impairment. Results: We studied (i) 2,3-DPG in red cells, and (ii) circulating EPO in AD, and both markers were unaffected by dementia. Disturbances of these oxygen-regulatory pathways do not appear to participate in brain hypoxia in AD.

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