scholarly journals Exploring the Serum Level of RE1 Silencing Transcription Factor in Alzheimer’s Disease

Author(s):  
Shashank Shekhar ◽  
Manjari Tripathi ◽  
A. B. Dey ◽  
Sharmistha Dey

Abstract Objective The aim of this study was to evaluate the serum RE1 silencing transcription factor (REST) level in Alzheimer’s disease (AD), mild cognitive impairment (MCI), and elderly controls by using surface plasmon resonance (SPR) technology. Materials and Methods In this case–control study of 133 subjects, 49 patients with AD, 49 patients with MCI, and 35 elderly controls were recruited. The REST protein concentrations were evaluated by SPR. The resonance unit for each sample was recorded and the concentration of serum REST of study group was derived from the standard curve. All the experiments were done in triplicates. Statistical analysis was done and p-value of < 0.05 was considered as statistically significant. Results A significant difference was observed in the Montreal Cognitive Assessment score, Hindi Mental State Examination scale (HMSE) score education, disease duration, and gender among the groups. A significant (p>0.0001) difference in the duration of disease between AD and MCI was observed. It was observed that the mean concentration of serum REST was not significantly (p = 0.266) different among the groups. Conclusion This study first time evaluated the serum levels of REST in AD, MCI and age-matched elderly controls. The rest levels were similar in all groups; however, it can provide a new direction to future blood-based biomarker studies of REST.

2021 ◽  
Author(s):  
Jiajia Fu ◽  
Yan Huang ◽  
Ting Bao ◽  
Ruwei Ou ◽  
Qianqian Wei ◽  
...  

Abstract Background: The ε2, ε3 and ε4 alleles of apolipoprotein (APO) E gene constitute a common polymorphism in most populations, among which the APOEε4 allele is known to increase both the susceptibility and severity of Alzheimer's Disease (AD), and it is also associated with lipid profiles. High serum total cholesterol (TC) level in middle age has been proven to be a risk factor for AD and its related pathology. In addition, sex may alter the risk associated with the APOEε4 allele, and gender-specific APOE gene interactions can alter the response to anticholinesterase therapy. Therefore, sex is an important factor in studying the relationship between the APOE gene, lipid profiles and AD, and the underlying mechanism. However, there are few studies on whether there are differences in the effects of APOEε2 and APOEε4 on AD patients and healthy people of different genders, respectively.Material and methods: A total of 549 participants, including 298 AD patients and 251 body mass index (BMI)-matched health controls (HCs), were enrolled. Lipid profiles and APOE genes in both AD patients and matched controls were determined. The cognitive functions of the AD patients were evaluated using the Mini-mental State Examination (MMSE) and the Montreal Cognitive Assessment (MoCA).Results: (1) The levels of TC and LDL in the AD group were higher than those in HCs. Subgroup analysis found that the AD patients with the APOEε4 allele had higher levels of TC and LDL than HCs carrying the APOEε4 allele, while in individuals without the APOEε4 allele. There was no significant difference in TG and HDL levels between the AD group and HCs. (2) The levels of TC and LDL in the APOEε4 carriers were higher than those in non-APOEε4 carriers. Subgroup analysis found that the increase of TC and LDL in the APOEε4 carriers was found in the AD and female populations, but not in HCs and male populations. (3) The levels of TC and LDL in the APOEε2 carriers were lower than those in non-APOEε2 carriers. Subgroup analysis found that the TC of APOEε2 carriers was lower than that of non-carriers in the male AD population, but not in the female AD population, female HCs, and male HCs. (4) The levels of TC, HDL and LDL in the female population were higher than the male population. (5) The increased LDL level may increase the risk of AD in female people carrying APOEε4.Conclusion: AD patients had higher TC and LDL levels than HCs, especially in the population with the APOEε4 allele. The levels of TC and LDL in the APOEε4 carriers were higher than those in non-APOEε4 carriers, especially in the female AD populations. The TC of APOEε2 carriers was lower than that of non-carriers, especially in male AD populations.


2012 ◽  
Vol 2012 ◽  
pp. 1-5 ◽  
Author(s):  
Brigitte Schreitmüller ◽  
Thomas Leyhe ◽  
Elke Stransky ◽  
Niklas Köhler ◽  
Christoph Laske

Background. Alzheimer's disease (AD) is the most common cause of dementia in the elderly. AD is characterized by the accumulation of amyloid plaques and neurofibrillary tangles and by massive neuronal loss in the brain. There is epidemiologic and pathologic evidence that AD is associated with vascular risk factors and vascular diseases, contributing to cerebral hypoperfusion with consecutive stimulation of angiogenesis and upregulation of proangiogenic factors such as Angiopoietin-1 (Ang-1).Methods. In the present study, we measured Ang-1 serum levels in 42 patients with AD, 20 patients with mild cognitive impairment (MCI), and in 40 healthy elderly controls by ELISA.Results. We found significantly increased Ang-1 serum levels in patients with AD compared to control subjects(P=0.003). There was no significant difference between MCI patients and healthy controls(P=0.553)or between AD and MCI patients(P=0.054). The degree of cognitive impairment as measured by the mini-mental status examination (MMSE) score was significantly correlated with the Ang-1 serum levels in all patients and healthy controls.Conclusions. We found significantly increased Ang-1 serum levels in AD patients. We could also show an association between Ang-1 serum levels and the cognitive status in all patients and healthy controls. Thus, serum Ang-1 could be a potential candidate for a biomarker panel for AD diagnosis.


2020 ◽  
Vol 4 (1) ◽  
pp. 379-391
Author(s):  
Alexander Andreev ◽  
Burak Erdinc ◽  
Kiran Shivaraj ◽  
Julia Schmutz ◽  
Olga Levochkina ◽  
...  

Background: Dementia is a spectrum of neurological diseases characterized by memory impairment and cognitive decline with the pathogenesis and effective management remaining elusive. Several studies have identified a correlation between anemia and Alzheimer’s disease and related dementias (ADRD); however, anemia subtypes and association with ADRD have yet to be studied conclusively. Objective: To study an association between ADRD and anemia of chronic inflammation. Methods: We conducted a retrospective case-control study of the patients, diagnosed with ADRD at Brookdale Hospital. Pair-wise comparisons between means of controls and cases in terms of iron studies and laboratory results were performed using a Mann–Whitney U test. Pair-wise comparisons between anemia subgroups (moderate and severe) were performed using a Two Sample proportion Z-Test, where for each couple of normally distributed population. Results: There was a total of 4,517 (1,274 ADRD group; 3,243 Control group) patients. There was significant difference in hemoglobin 10.15 versus 11.04 [p-value <0.001]. Iron studies showed a significant difference in ferritin 395±488.18 versus 263±1023.4 [p < 0.001], total iron binding capacity 225±84.08 versus 266±82.30 [p < 0.001] and serum iron level 64±39.34 versus 53±41.83 [p < 0.001]. Folic acid and vitamin B12 levels were normal in both groups. Severe and moderate anemia in the ADRD group were respectively 6.2% [95% CI: 4.2–8.4] and 13% [95% CI: 9.8–16.2] higher. Overall, incidence of moderate-to-severe anemia was found to be 19% higher in ADRD group [95% CI: 15.8–22.1]. Conclusion: We demonstrated an association between ADRD and anemia of chronic inflammation independent of age, renal function, and HgbA1C levels.


Bioimpacts ◽  
2019 ◽  
Vol 9 (4) ◽  
pp. 219-225 ◽  
Author(s):  
Elham Mehdizadeh ◽  
Mohammad Khalaj-Kondori ◽  
Zeinab Shaghaghi-Tarakdari ◽  
Saeed Sadigh-Eteghad ◽  
Mahnaz Talebi ◽  
...  

Introduction: Alzheimer’s disease (AD), which is a progressive neurodegenerative disorder, causes structural and functional brain disruption. MS4A6A, TREM2, and CD33 gene polymorphisms loci have been found to be associated with the pathobiology of late-onset AD (LOAD). In the present study, we tested the hypothesis of association of LOAD with rs983392, rs75932628, and rs3865444 polymorphisms in MS4A6A, TREM2, CD33 genes, respectively.Methods: In the present study, 113 LOAD patients and 100 healthy unrelated age- and gender-matched controls were selected. DNA was extracted from blood samples by the salting-out method and the genotyping was performed by RFLP-PCR. Electrophoresis was carried out on agarose gel. Sequencing was thereafter utilized for the confirmation of the results. Results: Only CD33 rs3865444 polymorphism revealed a significant difference in the genotypic frequencies of GG (P = 0.001) and GT (P = 0.001), and allelic frequencies of G (P = 0.033) and T (P = 0.03) between LOAD patients and controls. Conclusion: The evidence from the present study suggests that T allele of CD33 rs3865444 polymorphism is associated with LOAD in the studied Iranian population.


Author(s):  
Mengqi Liu ◽  
Jing Zhang ◽  
Linxiong Zong ◽  
Wenping Fan ◽  
Botao Wang ◽  
...  

Background: Callosal angle (CA) and Evans index (EI) had been considered as imaging biomarkers to diagnosis normal-pressure hydrocephalus as traditional MR measurement methods. Objective: The current study was aimed to evaluate the differential diagnostic value of CA and EI in the mild cognitive impairment (MCI) and Alzheimer’s disease (AD). Methods: Five-hundred and two subjects were selected from the Alzheimer's Disease Neuroimaging Initiative (ADNI) database, which included 168 normal controls (NC), 233 MCI and 101 AD patients. The structural MR images were interactively applied with multiplanar reconstruction to measure the CA and EI. Results: CA presented no significant difference among NC, MCI and AD groups (H value = 3.848, P value = 0.146), and EI was demonstrated the higher in MCI and AD groups than that in NC groups (P = 0.000 and 0.001, respectively). MCI group had significant larger EI (0.29±0.04) than that (0.27±0.03) in NC group in 70-75 years old sub-groups. ROC showed that the area under the curve was 0.704±0.045 for NC-MCI in 70-75 years old groups. The correlation analysis indicated that EI was significantly negatively related with MMSE scores of MCI patients (r = -0.131, P = 0.046). Conclusion: EI might serve as a screening imaging biomarker for MCI in 70-75 years old, and show limited differential value for the diagnosis of AD. CA could present no diagnostic value for MCI and AD in the current study.


SLEEP ◽  
2021 ◽  
Author(s):  
Adriano D S Targa ◽  
Iván D Benítez ◽  
Faridé Dakterzada ◽  
Anna Carnes ◽  
Montse Pujol ◽  
...  

Abstract Study Objectives To investigate the association between sleep and cognitive decline of patients with mild-moderate Alzheimer’s disease. Methods Observational, prospective study, including consecutive patients diagnosed with mild-moderate Alzheimer’s disease. Cerebrospinal fluid was collected for amyloid-beta, total-tau, and phospho-tau levels determination. Also, overnight polysomnography was performed, followed by neuropsychological evaluations at baseline and after 12 months of follow-up. Principal component analysis revealed two profiles of patients in terms of sleep: one with a propensity to deepen the sleep (deep sleepers) and the other with a propensity to spend most of the time in the lighter sleep stage (light sleepers). Results The cohort included 125 patients with a median [IQR] of 75.0 [72.0;80.0] years. Deep and light sleepers did not present differences in relation to the cerebrospinal fluid pathological markers and to the cognitive function at the baseline. However, there was a significant difference of -1.51 (95% CI: -2.43 to -0.59) in the Mini-mental state examination after 12 months of follow-up. Accordingly, sleep depth and cognitive decline presented a dose-response relationship (p-for-trend = 0.02). Similar outcomes were observed in relation to the processing speed (Stroop words test, p-value = 0.016) and to the executive function (Verbal fluency test, p-value = 0.023). Conclusions Considering the increased cognitive decline presented by light sleepers, the sleep profile may have a predictive role in relation to the cognitive function of patients with mild-moderate Alzheimer’s disease. The modifiable nature of sleep sets this behavior as a possible useful intervention to prevent a marked cognitive decline.


2018 ◽  
Vol 15 (7) ◽  
pp. 610-617 ◽  
Author(s):  
Huifeng Zhang ◽  
Dan Liu ◽  
Huanhuan Huang ◽  
Yujia Zhao ◽  
Hui Zhou

Background: β-amyloid (Aβ) accumulates abnormally to senile plaque which is the initiator of Alzheimer's disease (AD). As one of the Aβ-degrading enzymes, Insulin-degrading enzyme (IDE) remains controversial for its protein level and activity in Alzheimer's brain. Methods: The electronic databases PubMed, EMBASE, The Cochrane Library, OVID and Sinomed were systemically searched up to Sep. 20th, 2017. And the published case-control or cohort studies were retrieved to perform the meta-analysis. Results: Seven studies for IDE protein level (AD cases = 293; controls = 126), three for mRNA level (AD cases = 138; controls = 81), and three for enzyme activity (AD cases = 123; controls = 75) were pooling together. The IDE protein level was significantly lower in AD cases than in controls (SMD = - 0.47, 95% CI [-0.69, -0.24], p < 0.001), but IDE mRNA and enzyme activity had no significant difference (SMD = 0.02, 95% CI [-0.40, 0.43] and SMD = 0.06, 95% CI [-0.41, 0.53] respectively). Subgroup analyses found that IDE protein level was decreased in both cortex and hippocampus of AD cases (SMD = -0.43, 95% CI [-0.71, -0.16], p = 0.002 and SMD = -0.53, 95% CI [-0.91, -0.15], p = 0.006 respectively). However, IDE mRNA was higher in cortex of AD cases (SMD = 0.71, 95% CI [0.14, 1.29], p = 0.01), not in hippocampus (SMD = -0.26, 95% CI [-0.58, 0.06]). Conclusions: Our results indicate that AD patients may have lower IDE protease level. Further relevant studies are still needed to verify whether IDE is one of the factors affecting Aβ abnormal accumulation and throw new insights for AD detection or therapy.


Author(s):  
Ellen E. H. Johnson ◽  
Claire Alexander ◽  
Grace J. Lee ◽  
Kaley Angers ◽  
Diarra Ndiaye ◽  
...  

2021 ◽  
pp. 1-30
Author(s):  
Claudio Babiloni ◽  
Raffaele Ferri ◽  
Giuseppe Noce ◽  
Roberta Lizio ◽  
Susanna Lopez ◽  
...  

Background: In relaxed adults, staying in quiet wakefulness at eyes closed is related to the so-called resting state electroencephalographic (rsEEG) rhythms, showing the highest amplitude in posterior areas at alpha frequencies (8–13 Hz). Objective: Here we tested the hypothesis that age may affect rsEEG alpha (8–12 Hz) rhythms recorded in normal elderly (Nold) seniors and patients with mild cognitive impairment due to Alzheimer’s disease (ADMCI). Methods: Clinical and rsEEG datasets in 63 ADMCI and 60 Nold individuals (matched for demography, education, and gender) were taken from an international archive. The rsEEG rhythms were investigated at individual delta, theta, and alpha frequency bands, as well as fixed beta (14–30 Hz) and gamma (30–40 Hz) bands. Each group was stratified into three subgroups based on age ranges (i.e., tertiles). Results: As compared to the younger Nold subgroups, the older one showed greater reductions in the rsEEG alpha rhythms with major topographical effects in posterior regions. On the contrary, in relation to the younger ADMCI subgroups, the older one displayed a lesser reduction in those rhythms. Notably, the ADMCI subgroups pointed to similar cerebrospinal fluid AD diagnostic biomarkers, gray and white matter brain lesions revealed by neuroimaging, and clinical and neuropsychological scores. Conclusion: The present results suggest that age may represent a deranging factor for dominant rsEEG alpha rhythms in Nold seniors, while rsEEG alpha rhythms in ADMCI patients may be more affected by the disease variants related to earlier versus later onset of the AD.


2021 ◽  
Vol 80 (2) ◽  
pp. 673-681
Author(s):  
Jin Wang ◽  
Xiaojuan Guo ◽  
Wenhui Lu ◽  
Jie Liu ◽  
Hong Zhang ◽  
...  

Background: Vascular factors and mitochondria dysfunction contribute to the pathogenesis of Alzheimer’s disease (AD). DL-3-n-butylphthalide (NBP) has an effect in protecting mitochondria and improving microcirculation. Objective: The aim was to investigate the effect of donepezil combined NBP therapy in patients with mild-moderate AD. Methods: It was a prospective cohort study. 92 mild-moderate AD patients were classified into the donepezil alone group (n = 43) or the donepezil combined NBP group (n = 49) for 48 weeks. All patients were evaluated with Alzheimer’s Disease Assessment Scale-Cognitive subscale (ADAS-cog), Clinician’s Interview-Based Impression of Change plus caregiver input (CIBIC-plus), Alzheimer’s Disease Cooperative Study-Activities of Daily Living (ADCS-ADL), and Neuropsychiatric Inventory (NPI) every 12 weeks. All patients were monitored for adverse events (AEs). The efficacy was analyzed using multivariate logistic regression analysis. Results: The multivariate logistic regression analysis showed that the changes of ADAS-cog score (OR = 2.778, 95% CI: [1.087, 7. 100], p = 0.033) and ADCS-ADL score (OR = 2.733, 95% CI: [1.002, 7.459], p = 0.049) had significant difference between donepezil alone group and donepezil combined NBP group, while the changes of NPI (OR = 1.145, 95% CI: [0.463, 2.829], p = 0.769), MMSE (OR = 1.563, 95% CI: [0.615, 3.971], p = 0.348) and CIBIC-plus (OR = 2.593, 95% CI: [0.696, 9.685], p = 0.156) had no significant difference. The occurrence of AEs was similar in the two groups. Conclusion: Over the 48-week treatment period, donepezil combined NBP group had slower cognitive decline and better activities of daily living in patients with mild to moderate AD. These indicated that the multi-target therapeutic effect of NBP may be a new choice for AD treatment.


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