scholarly journals Plasma lipidome is dysregulated in Alzheimer’s disease and is associated with disease risk genes

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Yue Liu ◽  
Anbupalam Thalamuthu ◽  
Karen A. Mather ◽  
John Crawford ◽  
Marina Ulanova ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Classification Accuracy ◽  
Lipid Profiles ◽  
Lipid Classes ◽  
Differential Association ◽  
Control Group ◽  
Healthy Controls ◽  
Lipid Species ◽  
And Control

AbstractLipidomics research could provide insights of pathobiological mechanisms in Alzheimer’s disease. This study explores a battery of plasma lipids that can differentiate Alzheimer’s disease (AD) patients from healthy controls and determines whether lipid profiles correlate with genetic risk for AD. AD plasma samples were collected from the Sydney Memory and Ageing Study (MAS) Sydney, Australia (aged range 75–97 years; 51.2% male). Untargeted lipidomics analysis was performed by liquid chromatography coupled–mass spectrometry (LC–MS/MS). We found that several lipid species from nine lipid classes, particularly sphingomyelins (SMs), cholesterol esters (ChEs), phosphatidylcholines (PCs), phosphatidylethanolamines (PIs), phosphatidylinositols (PIs), and triglycerides (TGs) are dysregulated in AD patients and may help discriminate them from healthy controls. However, when the lipid species were grouped together into lipid subgroups, only the DG group was significantly higher in AD. ChEs, SMs, and TGs resulted in good classification accuracy using the Glmnet algorithm (elastic net penalization for the generalized linear model [glm]) with more than 80% AUC. In general, group lipids and the lipid subclasses LPC and PE had less classification accuracy compared to the other subclasses. We also found significant increases in SMs, PIs, and the LPE/PE ratio in human U251 astroglioma cell lines exposed to pathophysiological concentrations of oligomeric Aβ42. This suggests that oligomeric Aβ42 plays a contributory, if not causal role, in mediating changes in lipid profiles in AD that can be detected in the periphery. In addition, we evaluated the association of plasma lipid profiles with AD-related single nucleotide polymorphisms (SNPs) and polygenic risk scores (PRS) of AD. We found that FERMT2 and MS4A6A showed a significantly differential association with lipids in all lipid classes across disease and control groups. ABCA7 had a differential association with more than half of the DG lipids (52.63%) and PI lipids (57.14%), respectively. Additionally, 43.4% of lipids in the SM class were differentially associated with CLU. More than 30% of lipids in ChE, PE, and TG classes had differential associations with separate genes (ChE-PICALM, SLC24A4, and SORL1; PE-CLU and CR1; TG-BINI) between AD and control group. These data may provide renewed insights into the pathobiology of AD and the feasibility of identifying individuals with greater AD risk.

scholarly journals Brevican and Neurocan Peptides as Potential Cerebrospinal Fluid Biomarkers for Differentiation Between Vascular Dementia and Alzheimer’s Disease

2020 ◽  
pp. 1-13
Author(s):  
Karolina Minta ◽  
Gunnar Brinkmalm ◽  
Erik Portelius ◽  
Per Johansson ◽  
Johan Svensson ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cerebrospinal Fluid ◽  
Vascular Dementia ◽  
Extracellular Enzymes ◽  
Control Group ◽  
Healthy Controls ◽  
Clear Trend ◽  
Cerebrospinal Fluid Biomarkers

Background: Brevican and neurocan are central nervous system-specific extracellular matrix proteoglycans. They are degraded by extracellular enzymes, such as metalloproteinases. However, their degradation profile is largely unexplored in cerebrospinal fluid (CSF). Objective: The study aim was to quantify proteolytic peptides derived from brevican and neurocan in human CSF of patients with Alzheimer’s disease (AD) and vascular dementia (VaD) compared with controls. Methods: The first cohort consisted of 75 individuals including 25 patients with AD, 7 with mild cognitive impairment (MCI) diagnosed with AD upon follow-up, 10 patients with VaD or MCI diagnosed with VaD upon follow-up, and 33 healthy controls and cognitively stable MCI patients. In the second cohort, 31 individuals were included (5 AD patients, 14 VaD patients and 12 healthy controls). Twenty proteolytic peptides derived from brevican (n = 9) and neurocan (n = 11) were quantified using high-resolution parallel reaction monitoring mass spectrometry. Results: In the first cohort, the majority of CSF concentrations of brevican and neurocan peptides were significantly decreased inVaDas compared withADpatients (AUC = 0.83.0.93, p≤0.05) and as compared with the control group (AUC = 0.79.0.87, p ≤ 0.05). In the second cohort, CSF concentrations of two brevican peptides (B87, B156) were significantly decreased in VaD compared with AD (AUC = 0.86.0.91, p ≤ 0.05) and to controls (AUC = 0.80.0.82, p ≤ 0.05), while other brevican and neurocan peptides showed a clear trend to be decreased in VaD compared with AD (AUC = 0.64.80, p > 0.05). No peptides differed between AD and controls. Conclusion: Brevican and neurocan peptides are potential diagnostic biomarkers for VaD, with ability to separate VaD from AD.

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.

The Application Value of ApoE Gene Polymorphism in Alzheimer's Disease

2019 ◽  
Vol 9 (10) ◽  
pp. 1403-1407
Author(s):  
Cong Chen ◽  
Yuhui Zhang ◽  
Bin Chen ◽  
Chaosheng Zeng ◽  
Min Chen ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Gene Polymorphism ◽  
Apoe Genotype ◽  
Apoe Gene ◽  
Control Group ◽  
Apolipoprotein E Polymorphism ◽  
Abnormal Lipid Metabolism ◽  
And Control ◽  
Apoe Gene Polymorphism

To explore the association of apolipoprotein E polymorphism with Alzheimer's disease (AD), so as to provide possible research value for potential targeted therapy. 120 AD patients and 50 healthy volunteers were enrolled to extract fasting blood samples. ApoE gene polymorphism and blood lipids were tested in blood. ApoE gene and genotype frequency between AD group and control group were compared by PCR and sequencing methods. MMSE, CDR, and BPSD were used to determine the intelligence. ApoE genotype was detected by DNA microarray. ɛ4 carrier accounted for 45% in AD group, which was significantly elevated compared with control group (12%) (P < 0.05). TG, TC, and LDL-C levels were increased, while HDL-C was reduced in ɛ4 allele carriers (allP < 0.05). The MMSE scores of ApoEɛ4 genotype carriers in AD group were markedly lower than those of nonApoEɛ4 genotype carriers (P < 0.05) and control (P < 0.01). The proportion of dementia in ApoEɛ4 genotype carriers from AD group was apparently higher than the ɛ4 gene non-carriers (P < 0.05). The ApoEɛ4 gene is an AD risk factor. The changes of genotype and frequency of ApoEɛ4 gene are the main factors leading to abnormal lipid metabolism in AD patients, suggesting that ApoEɛ4 gene detection might be helpful for the early diagnosis and treatment of AD.

scholarly journals Investigation of five polymorphic DNA markers associated with late onset Alzheimer disease

Genetika ◽  
2013 ◽  
Vol 45 (2) ◽  
pp. 503-514 ◽  
Author(s):  
Jalal Gharesouran ◽  
Maryam Rezazadeh ◽  
Mohaddes Mojtaba
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Dna Markers ◽  
Neurodegenerative Disorder ◽  
Late Onset ◽  
The Elderly ◽  
Healthy Controls ◽  
Genotype Frequencies ◽  
Significant Difference ◽  
And Control

Alzheimer's disease is a complex neurodegenerative disorder characterized by memory and cognitive impairment and is the leading cause of dementia in the elderly. The aim of our study was to examine the polymorphic DNA markers CCR2 (+190 G/A), CCR5?32, TNF-? (-308 G/A), TNF-? (-863 C/A) and CALHM1 (+394 C/T) to determine the relationship between these polymorphisms and the risk of late onset Alzheimer's disease in the population of Eastern Azerbaijan of Iran. A total of 160 patient samples and 163 healthy controls were genotyped by PCR-RFLP and the results confirmed using bidirectional sequencing. Statistical analysis of obtained data revealed non-significant difference between frequency of CCR5?32 in case and control groups. The same result was observed for TNF-? (-863 C/A) genotype and allele frequencies. Contrary to above results, significant differences were detected in frequency of TNF-? (-308 G/A) and CCR2-64I genotypes between the cases and healthy controls. A weak significant difference observed between allele and genotype frequencies of rs2986017 in CALHM1 (+394 C/T; P86L) in patient and control samples. It can be concluded that the T allele of P86L variant in CALHM1 & +190 G/A allele of CCR2 have a protective role against abnormal clinical features of Alzheimer's disease.

scholarly journals Effects of Hand Exercise on Eating Action in Patients With Alzheimer’s Disease

2018 ◽  
Vol 34 (1) ◽  
pp. 57-62 ◽  
Author(s):  
Li-Li Chen ◽  
Hong Li ◽  
Xiao-Huan Chen ◽  
Shuang Jin ◽  
Qiu-Hua Chen ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Nursing Home ◽  
Exercise Group ◽  
Effective Intervention ◽  
Control Group ◽  
Daily Routine ◽  
Control Groups ◽  
And Control

We aim to investigate whether a popular hand exercise could be used to improve the action of eating in patients with Alzheimer’s disease (AD). A 6-month intervention was conducted in 60 patients with AD who live in a nursing home. They were divided into hand exercise and control groups. Patients of the control group maintained their daily routine. The improvement of Edinburgh Feeding Evaluation in Dementia scale in hand exercise group was significantly greater than in the control group ( P = .003). Significant differences in time of autonomous eating and time of simulated eating between patients in the hand exercise and control groups ( P < .05) were noted. The improvements in accuracy of eating action and coordination of eating action from baseline were significant in hand exercise group compared to the control group ( P = .020 and .014, respectively). Hand exercise is a safe and effective intervention to improve the feeding and eating of people with AD.

scholarly journals Autoantibodies to neurofibrillary tangles and brain tissue in Alzheimer's disease. Establishment of Epstein-Barr virus-transformed antibody-producing cell lines.

1987 ◽  
Vol 165 (1) ◽  
pp. 245-250 ◽  
Author(s):  
F Gaskin ◽  
B S Kingsley ◽  
S M Fu
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
B Cell ◽  
Cell Lines ◽  
Neurofibrillary Tangles ◽  
Control Group ◽  
Antibody Activity ◽  
Barr Virus ◽  
Epstein Barr ◽  
And Control

Multiple EBV-transformed B cell lines were established from five patients with a clinical diagnosis of Alzheimer's disease (AD) and six age-matched controls. The supernatants were screened for antibody activity against SDS-treated isolated neurofibrillary tangles (NFT). Reactive supernatants were identified from both the AD and control group. The frequencies of anti-NFT antibody-secreting lines were 6.3 and 1.6% for the AD and the control groups, respectively. A proportion of these supernatants also stained NFT in situ and neurons and/or glia in sections of the frontal and the temporal cortexes of autopsied AD and normal brains, as well as cells from three cell lines (HeLa, fibroblast, and neuroblastoma). Several patterns of staining were revealed by these supernatants, indicating different reactive antigens. One supernatant stained NFT and astrocytes in sections from AD brains. It did not stain sections from two normal brains. This cell line is the result of the immortalization of a circulating B cell making antibody specific for an antigen in AD. The present approach may provide new insights in the pathogenesis of AD.

scholarly journals Urinary Apolipoprotein C3 Is a Potential Biomarker for Alzheimer’s Disease

2020 ◽  
pp. 94-104
Author(s):  
Yumi Watanabe ◽  
Yoshitoshi Hirao ◽  
Kensaku Kasuga ◽  
Takayoshi Tokutake ◽  
Kaori Kitamura ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Urine Samples ◽  
Control Group ◽  
Label Free ◽  
Apolipoprotein C3 ◽  
Potential Biomarker ◽  
Proteomics Study ◽  
Urinary Levels ◽  
And Control

Introduction: Biomarkers of Alzheimer’s disease (AD) that can easily be measured in routine health checkups are desirable. Urine is a source of biomarkers that can be collected easily and noninvasively. We previously reported on the comprehensive profile of the urinary proteome of AD patients and identified proteins estimated to be significantly increased or decreased in AD patients by a label-free quantification method. The present study aimed to validate urinary levels of proteins that significantly differed between AD and control samples from our proteomics study (i.e., apolipoprotein C3 [ApoC3], insulin-like growth factor-binding protein 3 [Igfbp3], and apolipoprotein D [ApoD]). Methods: Enzyme-linked immunosorbent assays (ELISAs) were performed using urine samples from the same patient and control groups analyzed in the previous proteomics study (18 AD and 18 controls, set 1) and urine samples from an independent group of AD patients and controls (13 AD, 5 mild cognitive impairment [MCI], and 32 controls) from the National Center for Geriatrics and Gerontology Biobank (set 2). Results: In set 1, the crude urinary levels of ApoD, Igfbp3, and creatinine-adjusted ApoD were significantly higher in the AD group relative to the control group (p = 0.003, p = 0.002, and p = 0.019, respectively), consistent with our previous proteomics results. In set 2, however, the crude urinary levels of Igfbp3 were significantly lower in the AD+MCI group than in the control group (p = 0.028), and the levels of ApoD and ApoC3 did not differ significantly compared to the control group. Combined analysis of all samples revealed creatinine-adjusted ApoC3 levels to be significantly higher in the AD+MCI group (p = 0.015) and the AD-only group (p = 0.011) relative to the control group. Conclusion: ApoC3 may be a potential biomarker for AD, as validated by ELISA. Further analysis of ApoC3 as a urinary biomarker for AD is warranted.

scholarly journals Alexithymia in Alzheimer’s Disease

2020 ◽  
Vol 10 (1) ◽  
pp. 44
Author(s):  
Eva Mª Arroyo-Anlló ◽  
Corinne Souchaud ◽  
Pierre Ingrand ◽  
Jorge Chamorro Sánchez ◽  
Alejandra Melero Ventola ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cognitive Abilities ◽  
Rating Scale ◽  
Mood State ◽  
Neuropsychological Test ◽  
Control Group ◽  
Control Groups ◽  
Significant Difference ◽  
And Control

Alexithymia is widely recognized as the inability to identify and express emotions. It is a construct which consists of four cognitive traits such as difficulty in identifying feelings, describing feelings to others, externally oriented thinking, and limited imaginative capacity. Several studies have linked alexithymia to cognitive functioning, observing greater alexithymia scores associated with poorer cognitive abilities. Despite Alzheimer’s disease (AD) being a neurodegenerative pathology characterized by cognitive troubles from the early stages, associated to behavioral and emotional disturbances, very few investigations have studied the alexithymia in AD. These studies have shown that alexithymia scores—assessed with Toronto Alexithymia Scale (TAS)—were greater in AD patients than healthy participants. The objective of the study was to investigate if the alexithymia was present in patients with mild AD. We hypothesized that the AD group would show more alexithymia features than the control group. We evaluated 54 subjects, including 27 patients diagnosed with mild AD and 27 normal healthy controls, using the Shalling Sifneos Psychosomatic Scale (SSPS-R) and a neuropsychological test battery. Using non-parametric statistical analyses—Wilcoxon and Mann–Whitney U tests—we observed that the SSPS-R scores were similar in the AD and control groups. All participants showed SSPS-R scores below to 10 points, which means no-alexithymia. We did not find significant correlations between SSPS-R scores and cognitive variables in both groups (p > 0.22), but we observed a negative association between name abilities and alexithymia, but it does not reach to significance (p = 0.07). However, a significant correlation between SSPS-R score and mood state, assessed using Zerssen Rating Scale, was found in both groups (p = 0.01). Because we did not find a significant difference in the alexithymia assessment between both subject groups, pot hoc analyses were computed for each item of the SSPS-R. We made comparisons of alexithymic responses percentages in each SSPS-R item between AD and control groups, using Fisher’s test. We observed that AD patients produced more alexithymic responses in some items of SSPS-R test than the control group, particularly about difficulties to find the words to describe feelings, as well as difficulties of imagination capacity and externally oriented thinking. The present results do not confirm our hypothesis and they do not support the results of previous studies revealing great alexithymia in AD.

scholarly journals Analysis of the Proteomic Profiling of Brain Tissue in Alzheimer's Disease

2001 ◽  
Vol 17 (4) ◽  
pp. 247-257 ◽  
Author(s):  
T. Tsuji ◽  
S. Shimohama
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Proteome Analysis ◽  
Control Group ◽  
Normal Brain ◽  
Proteomic Profiling ◽  
Brain Proteins ◽  
Reference Map ◽  
And Control ◽  
Pathologic Processes

In proteome analysis, it is necessary to separate proteins as a first step prior to characterization. Thus, the overall performance of the analysis depends strongly on the separation tool, which is usually two-dimensional electrophoresis (2DE). We have utilized 2DE to begin characterization of the complex pathologic processes in Alzheimer's disease (AD). In the present study, we show how a reliable 2-DE database of brain proteins in Alzheimer's disease was created, improving reproducibility by using an immobilized pH gradient (IPG) for the first dimension gel electrophoresis. The recent progress in this field, and future prospects in this area are also discussed. Preparation of brain proteins into a suitable solubilized state enabled us to separate over 1000 well-defined protein spots in each 2-DE. A comparison of the density of the spots identified on the reference map between the AD and control group, showed that 5 protein spots were significantly increased, 28 spots were significantly decreased and 7 spots were specifically detected in AD. Two spots among those significantly increased and one spot among those significantly decreased were identified as GFAP related. It is hoped that comparative studies to identify, quantitate, and characterize the proteins differentially expressed in normal brain versus diseased brain will give insight into the mechanisms of pathogenesis and allow the development of a strategy to control both the etiology and course of the diseases.

scholarly journals Polymorphisms of Proinflammatory Cytokines in Relation to APOE Epsilon 4 and Risk of Alzheimer’s Disease in the Lithuanian Population

Medicina ◽  
2019 ◽  
Vol 55 (10) ◽  
pp. 689
Author(s):  
Pšemeneckienė ◽  
Petrikonis ◽  
Rastenytė
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Proinflammatory Cytokines ◽  
Risk Identification ◽  
Control Group ◽  
Study Population ◽  
Independent Risk Factors ◽  
And Gender ◽  
And Control ◽  
The Impact

Background and objective: Neuroinflammation is one of the pathological pathways of Alzheimer’s disease (AD), mediating the progression of neurodegeneration. Polymorphisms of proinflammatory cytokines have been linked to increased AD risk. Identification of certain combinations of polymorphisms could help predict disease in its preclinical stage. The aim of the study was to evaluate differences in the prevalence of TNFα –850T (rs1799724), IL1A –889T (rs1800587), and IL6 –174C (rs1800795, Intron type) polymorphisms between AD patients and healthy controls (HC) and determine the impact of these SNPs in combination with the APOEε4 allele on AD risk. Materials and Methods: The study population is comprised of 107 patients with sporadic AD (AD group) and age- and gender-matched 110 persons without impaired cognitive functions (control group). TNFα –850C > T polymorphism was revealed by a PCR and restriction fragment length polymorphism (RFLP) method. Real time PCR was used for IL1A and IL6 SNP genotyping. APOEε genotyping was done via hybridization method. Results: The frequencies of TNFα –850T, IL1A –889T, IL6 –174C allele and genotype did not differ between the AD and HC groups (p > 0.05). IL6 –174C was not in HWE, and it was not analysed further. APOEε4 allele (p = 0.001) and 3/4 and 4/4 genotypes (p = 0.005) were more prevalent in AD patients. APOEε4 carriage increased the risk of AD (OR 2.65, p = 0.001), while TNFα –850T and IL1A –889T polymorphisms were not found as significant independent risk factors for AD. The presence of at least one IL1A –889T allele in combination with APOEε4+ was associated with a lower risk of AD (OR 2.24, p = 0.047) than the carriage of APOEε4+ alone (OR 2.70, p = 0.015). Conclusions: No significant differences of TNFα –850, IL1A –889, and IL6 –174 polymorphisms frequencies were found between AD and control groups. In APOEε4 carriers IL1A –889T polymorphism was found to reduce the AD risk determined by APOEε4 alone.

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