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.

scholarly journals Prevalence of Comorbidities in Individuals Diagnosed and Undiagnosed with Alzheimer’s Disease in León, Spain and a Proposal for Contingency Procedures to Follow in the Case of Emergencies Involving People with Alzheimer’s Disease

2020 ◽  
Vol 17 (10) ◽  
pp. 3398
Author(s):  
Macrina Tortajada-Soler ◽  
Leticia Sánchez-Valdeón ◽  
Marta Blanco-Nistal ◽  
José Alberto Benítez-Andrades ◽  
Cristina Liébana-Presa ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cognitive Disorders ◽  
Cross Sectional Study ◽  
Control Group ◽  
Cross Sectional ◽  
Emergency Procedures ◽  
And Control ◽  
Similar Incidence

Background: Alzheimer’s disease (AD) which is the most common type of dementia is characterized by mental or cognitive disorders. People suffering with this condition find it inherently difficult to communicate and describe symptoms. As a consequence, both detection and treatment of comorbidities associated with Alzheimer’s disease are substantially impaired. Equally, action protocols in the case of emergencies must be clearly formulated and stated. Methods: We performed a bibliography search followed by an observational and cross-sectional study involving a thorough review of medical records. A group of AD patients was compared with a control group. Each group consisted of 100 people and were all León residents aged ≥65 years. Results: The following comorbidities were found to be associated with AD: cataracts, urinary incontinence, osteoarthritis, hearing loss, osteoporosis, and personality disorders. The most frequent comorbidities in the control group were the following: eye strain, stroke, vertigo, as well as circulatory and respiratory disorders. Comorbidities with a similar incidence in both groups included type 2 diabetes mellitus, glaucoma, depression, obesity, arthritis, and anxiety. We also reviewed emergency procedures employed in the case of an emergency involving an AD patient. Conclusions: Some comorbidities were present in both the AD and control groups, while others were found in the AD group and not in the control group, and vice versa.

scholarly journals Adequacy of food consumption in elderly Alzheimer’s disease in a community of Southern Brazil: a Cross-sectional study

F1000Research ◽  
2018 ◽  
Vol 7 ◽  
pp. 671
Author(s):  
Glaucia Renee Hilgemberg ◽  
Aline Jacoski de Oliveira Krüger da Silva ◽  
Bárbara Luisa Fermino ◽  
Camila Diedrich ◽  
Simone Carla Benincá ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Nutritional Status ◽  
Neuronal Loss ◽  
Great Difficulty ◽  
Amyloid Peptide ◽  
Control Group ◽  
Food Record ◽  
Cross Sectional ◽  
Significant Difference

Background: Alzheimer's disease (AD) is the most common cause of dementia, with a multifactorial etiology, in which the person has great difficulty identifying feelings of hunger, satiety, and feeding, which may affect their nutritional status. Pathologically, it is associated with neurodegeneration of synapses followed by neuronal loss, accompanied by glial proliferation surrounded by neurofibrillary tangles, beta-amyloid peptide (Aβ) deposition, inflammation and cerebrovascular injury hindering the ability to perform activities of daily living. This study aimed to analyze quantitatively the differences between an elderly group with AD and a control group, in terms of macro and micronutrient consumption evaluation. Methods: the study involved 69 participants who were assessed via collection of anthropometric measurements (weight, height and body mass index) with nutritional status being assessed by 24-hour food recall and three-day food record. Cognitive assessments were performed using the Mini-Mental State Examination (MMSE) and Clinical Dementia Ranting (CDR). Results: The intake of lipids in patients with severe dementia, was lower (p <0.05). The consumption of proteins showed a decrease with demential advance. For vitamins, there was a significant difference (p <0.05) in the amount of thiamine, niacin, vitamin D, E and K and calcium, chromium and iodine minerals, which were significantly reduced in AD patients (p <0.05). Conclusions: Decreases in macronutrient and micronutrient consumption may result in a consequent impairment of nutritional status, dementia progression, and decreased quality and life expectancy of elderly patients with AD.

scholarly journals Selenium concentrations in elderly people with Alzheimer’s disease: a cross-sectional study with control group

2021 ◽  
Vol 74 (suppl 2) ◽  
Author(s):  
Carlos Queiroz do Nascimento ◽  
João Araújo Barros-Neto ◽  
Nathalia Fidelis Lins Vieira ◽  
José Antonio Menezes-Filho ◽  
Sabrina Joanny Felizardo Neves ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Plasma Concentrations ◽  
Atomic Absorption Spectrophotometry ◽  
Cross Sectional Study ◽  
Elderly Group ◽  
Control Group ◽  
Sectional Study ◽  
Disease Group ◽  
Cross Sectional

ABSTRACT Objective: To investigate possible differences in plasma and erythrocyte concentrations of selenium among elderly with and without a diagnosis of Alzheimer’s disease (AD). Methods: Cross-sectional study, performed with an elderly group with Alzheimer’s disease, diagnosed by a geriatric doctor, and compared to an elderly group without the disease, equaling gender, education, and age. Atomic absorption spectrophotometry determined plasma and erythrocyte concentrations of total selenium (Set). Results: The mean age was 74.41±7.1 years in the Alzheimer’s disease group and 71.46±5.1 years among the control group. The Alzheimer’s disease group presented lower plasma concentrations (mean of 45.29±14.51 µg/dL vs. 55.14±14.01 µg/dL; p=0.004), and erythrocyte Set (median of 56.36 µg/L vs. 76.96 µg/L; p<0.001). The logistic regression model indicated an association between erythrocyte Set concentrations and diagnosis of Alzheimer’s disease (p=0.028). Conclusion: Elderly with Alzheimer’s disease present lower selenium concentrations in the evaluated organic compartments.

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.

scholarly journals Relation between Alpha-Synuclein and Core CSF Biomarkers of Alzheimer’s Disease

Medicina ◽  
2021 ◽  
Vol 57 (9) ◽  
pp. 954
Author(s):  
Victoria Monge-García ◽  
María-Salud García-Ayllón ◽  
Javier Sáez-Valero ◽  
José Sánchez-Payá ◽  
Francisco Navarrete-Rueda ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Lewy Body Dementia ◽  
Alpha Synuclein ◽  
Tau Proteins ◽  
Control Group ◽  
P Value ◽  
Csf Biomarkers ◽  
Cross Sectional ◽  
Spearman Test

Background: Alzheimer’s disease (AD) is characterized by the presence of β-amyloid plaques and neurofibrillary tangles, while Lewy body dementia (LBD) is characterized by α-synuclein (α-syn) inclusions. Some authors examine α-syn protein in the neurodegeneration process of AD and propose to consider cerebrospinal fluid (CSF) α-syn as a possible additional biomarker to the so-called “core” of AD. Objective: To determine whether there is a correlation between α-syn levels and “core” AD biomarkers in patients with mild cognitive impairment (MCI). Materials and methods: In total, 81 patients in the early stages of MCI were selected from the outpatient dementia consultation in Alicante General Hospital. Using a cross-sectional case–control design, patients were analyzed in four groups: stable MCI (MCIs; n = 25), MCI due to AD (MCI-AD; n = 32), MCI due to LBD (MCI-LBD; n = 24) and a control group of patients with acute or chronic headache (Ctrl; n = 18). Correlation between CSF protein levels in the different groups was assessed by the Rho Spearman test. Results: We found positive correlations between T-tau protein and α-syn (ρ = 0.418; p value < 0.05) and p-tau181p and α-syn (ρ = 0.571; p value < 0.05) exclusively in the MCI-AD group. Conclusion: The correlation found between α-syn and tau proteins in the first stages of AD support the involvement of α-syn in the pathogenesis of AD. This result may have clinical and diagnostic implications, as well as help to apply the new concept of “precision medicine” in patients with MCI.

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 NLRC3 delays the progression of AD in APP/PS1 mice via inhibiting PI3K activation

2019 ◽  
Author(s):  
lihuang zha ◽  
Zai-xin Yu ◽  
Shuhong Guo ◽  
Li Zhou ◽  
Wen Guo ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Learning And Memory ◽  
Inflammatory Responses ◽  
Behavioral Experiment ◽  
Morris Water Maze Test ◽  
Control Group ◽  
Hippocampus Slice ◽  
Pi3k Activation ◽  
Brain Tissues

Abstract Background/Aims: NLRC3 inhibits inflammatory responses. Epidemiological studies indicate that neuroinflammation induces and accelerates the onset of Alzheimer's disease (AD). This study was designed to determine whether NLRC3 plays a role in neuroinflammation, Aβ accumulation and neuroprotection in AD mice. Methods: Thirty 12-month-old APP/PS1 transgenic mice were randomized into three groups as model group, APP/PS1 +LVCON307 and APP/PS1 +LV-NLRC3 group. Ten 12-month-old wild-type C57 mice were chosen as control group. Mice in APP/PS1 +LVCON307 and APP/PS1 +LV-NLRC3 group were injected with LVCON307 or LV-NLRC3 through intracerebroventricular injection. Six months after LVCON307 or LV-NLRC3 injection, We carried out Morris water maze test on mice and harvested their brain tissues after the behavioral experiment. The deposition of amyloid protein and the changes of Nissle bodies were observed by ThS and Nissle staining. The expressions of NLRC3, 6E10, GFAP, Iba1, NeuN and PI3K were detected by immunohistochemistry or immunofluorescence. Western blot was used to analyze the expression of NLRC3, PI3K, GFAP and Iba1. Results: The expression of NLRC3 is down-regulated in brain tissues of APP/PS1 mice. Mice in APP/PS1 group had a significant attenuation of learning and memory ability compared to the control group, the ability of learning and memory was improved in APP/PS1 +LV-NLRC3 mice. The expression of 6E10, GFAP, Iba1 and PI3K in brain and hippocampus slice of APP/PS1 and APP/PS1 + LVCON307 mice were significantly higher than those of the control group, while the expression of NLRC3 and NeuN was significantly lower than that of the control group. After overexpression of NLRC3, the expression of 6e10, GFAP, Iba1 and PI3K in APP/PS1 + LV-NLRC3 group was significantly lower than that in APP/PS1 and APP/PS1 + LVCON307 group, while the expression of NLRC3 and NeuN was significantly higher than that in APP/PS1 and APP/PS1 + LVCON307 group. NLRC3 co-localized with NeuN. PI3K activation with 740YP increased the expression of GFAP and Iba-1 in hippocampus with exogenous NLRC3 protein. Conclusion: NLRC3 may play an important role in the development and progression of AD. Down-regulation of NLRC3 can lead to the activation of PI3K, resulting in abnormal plaque deposition, glial cell activation and neuron loss during AD. NLRC3 delays the progression of AD in APP/PS1 mice via inhibiting PI3K activation. Keywords: NLRC3 • inflammation • Aβ • neuron •PI3K •Alzheimer's disease

scholarly journals Regional cerebral blood flow correlates of visuospatial tasks in Alzheimer's disease

2008 ◽  
Vol 14 (6) ◽  
pp. 1034-1045 ◽  
Author(s):  
WILLIAM J. TIPPETT ◽  
SANDRA E. BLACK
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cerebral Perfusion ◽  
Right Hemisphere ◽  
Single Photon ◽  
Photon Emission ◽  
Brain Network ◽  
Control Group ◽  
Cross Sectional ◽  
Visuospatial Tasks

AbstractThis study investigated the role of visuospatial tasks in identifying cognitive decline in patients with Alzheimer's disease (AD), by correlating neuropsychological performance with cerebral perfusion measures. There were 157 participants: 29 neurologically healthy controls (age: 70.3 ± 6.6, MMSE ≥ 27), 86 patients with mild AD (age: 69.18 ± 8.28, MMSE ≥ 21) and 42 patients moderate/severe AD (age: 68.86 ± 10.69, MMSE 8–20). Single Photon Emission Computerized Tomography (SPECT) was used to derive regional perfusion ratios, and correlated using partial least squares (PLS) with neuropsychological test scores from the Benton Line Orientation (BLO) and the Rey-Osterrieth Complex Figure (RO). Cross-sectional analysis demonstrated that mean scores differed in accordance with disease status: control group (BLO 25.5, RO 33.3); mild AD (BLO 20.1, RO 25.5); moderate/severe AD (BLO 10.7, RO 16). Correlations were observed between BLO/RO and right parietal SPECT regions in the AD groups. Visuospatial performance, often undersampled in cognitive batteries for AD, is clearly impaired even in mild AD and correlates with functional deficits as indexed by cerebral perfusion ratios on SPECT implicating right hemisphere circuits. Furthermore, PLS reveals that usual spatial tasks probe a distributed brain network in both hemispheres including many areas targeted by early AD pathology. (JINS, 2008, 14, 1034–1045.)

scholarly journals The Role of Galanin, Alarin, Irisin, PGC1-Α and BDNF in the Pathophysiology of Alzheimer's disease

2021 ◽  
Vol 8 (06) ◽  
pp. 5498-5507
Author(s):  
Huseyin Fatih Gul ◽  
Caner Yildirim ◽  
Can Emre Erdogan ◽  
Ozlem Gul ◽  
Nazlı Koc
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Control Group ◽  
Peroxisome Proliferator ◽  
The Novel ◽  
Cross Sectional ◽  
Peroxisome Proliferator Activated Receptor ◽  
The Mean ◽  
Positive Correlations

The roles of novel peptides such as peroxisome proliferator-activated receptor gamma coactivator 1- alpha (PGC1-α), irisin, brain-derived neurotrophic factor (BDNF), galanin and alarin in Alzheimer's disease (AD) are not fully known. It was aimed to plasma levels of the novel peptides that may affect the pathophysiology of AD were examined. This study was conducted as a cross-sectional. The study consisted of two groups, including 45 newly diagnosed individuals with AD and 45 healthy individuals. The peptide levels in plasma samples collected from the groups were measured by the ELISA method. The mean plasma peptide levels and age differences, between the groups, and the correlations between them were analyzed by the statistically. The means ages of both groups were over 65 years old. When plasma PGC1-α, irisin, BDNF, galanin, and alarin levels between the groups were examined, decreases were found in the group with AD (3.56±0.79ng/mL, 16.33±4.07ng/mL, 3.36±1.47ng/mL, 13.93±4.24ng/L, 31.99±11.89pg/mL, respectively) compared to the control group (4.23±1.31ng/mL, 22.19±9.61ng/mL, 4.58±2.10ng/mL, 14.4±9.01ng/L, 54.93±15.80pg/mL, respectively). In the negative correlations observed between age and plasma peptide levels. Significant positive correlations were observed between plasma PGC1-α levels and irisin, alarin, and BDNF, and the significant positive correlations were also observed between plasma BDNF levels and irisin and alarin. As far as we know, the study is the first report in which the peptides mentioned in AD were examined together. We consider that more detailed studies are needed to shed light on the roles and mechanisms of these peptides in AD.

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.

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