Plasma Clusterin as a Potential Biomarker for Alzheimer’s Disease-A Systematic Review and Meta-analysis

2019 ◽  
Vol 16 (11) ◽  
pp. 1018-1027
Author(s):  
XinRui Shi ◽  
BeiJia Xie ◽  
Yi Xing ◽  
Yi Tang
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Regression Model ◽  
Disease Severity ◽  
Cox Regression ◽  
Meta Analysis ◽  
Control Groups ◽  
Potential Biomarker ◽  
The Difference ◽  
And Control

Background: Plasma clusterin has been reported to be associated with the pathology, prevalence, severity, and rapid clinical progress of Alzheimer’s Disease (AD). However, whether plasma clusterin can be used as a biomarker of AD is inconsistent and even conflicting. Objective: We conducted this study to evaluate the potential of plasma clusterin as the biomarker of AD. Method: PubMed, Embase, and Cochrane databases were systematically searched for studies on the relationship between plasma clusterin levels and AD diagnosis, risk and disease severity. We also compared the difference in Cerebrospinal Fluid (CSF) clusterin levels between AD and control groups. We converted and pooled data using standardized mean difference, Pearson linear regression model and the Cox regression model. Results: A total of 17 articles and 7228 individuals, including 1936 AD were included. The quality ranged from moderate to high. There was no difference in plasma clusterin between AD and control groups (SMD= 0.19 [-0.10, 0.48], p=0.20). Plasma clusterin levels were not correlated with the risk (RR=1.03 [0.97-1.09], p=0.31), the MMSE scores (R=0.33 [-0.06, 0.71], p= 0.09), and the integrated neuropsychological measurements (R=0.21 [-0.20, 0.63], p=0.31) of AD. Additionally, there was no difference in CSF clusterin between AD and control groups (SMD=1.94 [ -0.49, 4.37], p=0.12). Conclusion: Our meta-analysis suggested no relationship between plasma clusterin levels and the diagnosis, risk, and disease severity of AD and no difference in the CSF clusterin between AD and the control groups. Overall, there is no evidence to support plasma clusterin as a biomarker of AD based on the pooled results.

Abstract 2211: Statin Therapy May Increase the Risk of Intracerebral Hemorrhage: A Meta-analysis of 26 Randomized Controlled Trials

Stroke ◽  
2012 ◽  
Vol 43 (suppl_1) ◽  
Author(s):  
James S McKinney ◽  
William J Kostis ◽  
John B Kostis
Keyword(s):  
Statin Therapy ◽  
Meta Analysis ◽  
Active Group ◽  
Controlled Trials ◽  
Control Groups ◽  
Randomized Controlled ◽  
All Cause Mortality ◽  
Group A ◽  
The Difference ◽  
And Control

Introduction--- Statin therapy decreases the risk of myocardial infarction and ischemic stroke. However, an increased risk of intracerebral hemorrhage (ICH) has been observed in some studies. To investigate this issue we performed a meta-analysis of all randomized controlled trials (RCTs) using statins that reported ICH. Methods--- We performed a Medline literature search through March 18, 2011 and identified additional RCTs by reviewing reference lists of retrieved studies and prior meta-analyses. All RCTs of statin therapy versus placebo or high dose versus low dose statin therapy that reported ICH or hemorrhagic stroke were included. The primary outcome variable was ICH. 26 RCTs were included. All analyses used random effects models and heterogeneity was not observed in any of the analyses. Results--- 84 831 subjects were included in the Active group, and 84 851 in the Control group. A trend towards a higher incidence of ICH was observed in the Active treatment group compared to Control (OR = 1.15; 95% CI = 0.91 to 1.45, p =0.24) (Figure). Significant relationships were not observed between the log OR for ICH with achieved LDL in the Active group (slope = 0.0002; 95% CI = -0.0098 to 0.0101, p =0.96) or with the difference in LDL drop between the Active and Control groups (slope = 0.0030; 95% CI = -0.0089 to 0.0149, p =0.62). Total stroke (OR = 0.84; 95% CI = 0.78 to 0.91, p <0.001) and all-cause mortality (OR = 0.91; 95% CI = 0.86 to 0.96, p <0.001) were significantly reduced in the Active group. A significant relationship between all-cause mortality and the difference in LDL drop between the Active and Control groups was observed (slope = -0.0030; 95% CI = -0.0009 to -0.0051, p<0.005). There was not evidence of publication bias in this meta-analysis. Conclusions--- Active therapy was associated with a trend towards increased ICH in this meta-analysis of 26 RCTs of statin therapy. However, this risk does not appear to be related to the degree of decline or achieved LDL. The risk of ICH is offset by a significant reduction in ischemic stroke and all-cause mortality and should not dissuade practitioners from prescribing statins in otherwise appropriate patients.

A Novel Polymorphic Purine Complex at the Upstream Region of the Human Caveolin-1 Gene and Risk of Alzheimer’s Disease

2009 ◽  
Vol 24 (S1) ◽  
pp. 1-1
Author(s):  
M. Ohadi ◽  
Y. Heshmati ◽  
A. Mirabzadeh ◽  
H.R. Khorram Khorshid ◽  
K. Kamali
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Late Onset ◽  
Upstream Region ◽  
Case Group ◽  
Control Groups ◽  
Gene Encoding ◽  
Aberrant Expression ◽  
Caveolin 1 ◽  
And Control

Crucial interaction of caveolin-1 (CAV1) with beta- and gamma-secretases, and aberrant expression of the gene encoding this protein in Alzheimer's disease (AD) support a role for CAV1 in the pathophysiology of this disease.We report a novel polymorphic purine complex stretching ~150 bp of genomic DNA at the 1.5 kb upstream region of the human CAV1 gene, alleles and genotypes of which are associated with sporadic late-onset AD. Extra-short alleles were observed in the case group that were absent in the control subjects. Increased homozygosity for haplotypes was also observed at this region in the Alzheimer's cases, for those alleles and allele lengths shared by the case and control groups [(c2=30.75, df=1, p< .000, OR=4.54, CI 95% (2.56-8.3)]. This region contains GGAA and GAAA motifs, the consensus binding sites for the Ets and IRF family transcription factors, respectively, and is highly conserved in distantly-related non-human primates in respect with location and motif sequence. The effect of this complex sequence on the expression of CAV1, and the related mechanisms in the pathophysiology of AD remain to be clarified.

scholarly journals Measuring serum oestradiol in women with Alzheimer's disease: the importance of the sensitivity of the assay method

2003 ◽  
pp. 67-72 ◽  
Author(s):  
E Hogervorst ◽  
J Williams ◽  
M Combrinck ◽  
A David Smith
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Robust Regression ◽  
Meta Analysis ◽  
Hormone Replacement ◽  
Assay Method ◽  
Sensitive Assay ◽  
Significant Difference ◽  
Low Levels ◽  
The Difference

OBJECTIVE: Oestrogens could be protective against the development of Alzheimer's disease (AD) but reports on oestrogen levels in AD have been conflicting. DESIGN AND METHODS: A meta-analysis using robust regression was carried out to assess whether the sensitivity of the assays of past studies had affected the reported level of total oestradiol. We had also measured total oestradiol in women with AD (n=66) and controls (n=62) not using hormone replacement therapy. We used two assays for total oestradiol to assess the difference between sensitive (radioimmunoassay with a specific rabbit antibody: 3 pmol/l) and relatively insensitive (immunoassay: 37 pmol/l) assays. RESULTS: Meta-analysis using robust regression indicated that insensitive assays gave higher levels of total oestradiol when many samples fall below the level of sensitivity of the method. Earlier reports of low levels of total oestradiol in AD might be explained by this phenomenon, since total oestradiol levels (using the sensitive assay) in our controls were one third of those reported in the earlier studies. Using the sensitive assay we found that women with AD had significantly (P<0.01) higher levels (26+/-13 pmol/l) of total oestradiol than controls (21+/-13 pmol/l). Using the insensitive assay, there was no significant difference in the levels of total oestradiol. CONCLUSIONS: The sensitivity of the assay determines the reported value of the oestradiol levels. Studies using a sensitive assay do not report significantly lower levels of total oestradiol in women with AD. This weighs against the hypothesis that low levels of total oestradiol are a risk factor for AD.

scholarly journals Blood-Based ATN Biomarkers of Alzheimer’s Disease: A Meta-Analysis

2021 ◽  
Vol 79 (1) ◽  
pp. 177-195
Author(s):  
Ivan Koychev ◽  
Katrin Jansen ◽  
Alina Dette ◽  
Liu Shi ◽  
Heinz Holling
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Single Molecule ◽  
Meta Analysis ◽  
Random Effect ◽  
Neurofilament Light ◽  
Meta Analyses ◽  
And Control ◽  
T Tau ◽  
Biological State

Background: The Amyloid Tau Neurodegeneration (ATN) framework was proposed to define the biological state underpinning Alzheimer’s disease (AD). Blood-based biomarkers offer a scalable alternative to the costly and invasive currently available biomarkers. Objective: In this meta-analysis we sought to assess the diagnostic performance of plasma amyloid (Aβ40, Aβ42, Aβ42/40 ratio), tangle (p-tau181), and neurodegeneration (total tau [t-tau], neurofilament light [NfL]) biomarkers. Methods: Electronic databases were screened for studies reporting biomarker concentrations for AD and control cohorts. Biomarker performance was examined by random-effect meta-analyses based on the ratio between biomarker concentrations in patients and controls. Results: 83 studies published between 1996 and 2020 were included in the analyses. Aβ42/40 ratio as well as Aβ42 discriminated AD patients from controls when using novel platforms such as immunomagnetic reduction (IMR). We found significant differences in ptau-181 concentration for studies based on single molecule array (Simoa), but not for studies based on IMR or ELISA. T-tau was significantly different between AD patients and control in IMR and Simoa but not in ELISA-based studies. In contrast, NfL differentiated between groups across platforms. Exosome studies showed strong separation between patients and controls for Aβ42, t-tau, and p-tau181. Conclusion: Currently available assays for sampling plasma ATN biomarkers appear to differentiate between AD patients and controls. Novel assay methodologies have given the field a significant boost for testing these biomarkers, such as IMR for Aβ, Simoa for p-tau181. Enriching samples through extracellular vesicles shows promise but requires further validation.

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 Inter-Individual Differences in Exercise Responses in Alzheimer’s Disease

2020 ◽  
Vol 4 (Supplement_1) ◽  
pp. 188-188
Author(s):  
Fang Yu ◽  
Dereck Salisbury ◽  
Michelle Mathiason
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Individual Differences ◽  
Aerobic Exercise ◽  
Aerobic Fitness ◽  
Cognitive Responses ◽  
Walk Test ◽  
Control Groups ◽  
Ergometer Exercise ◽  
And Control

Abstract Aerobic exercise is widely supported as a disease-modifying treatment for Alzheimer’s disease (AD) in animal models; however, its effects on cognition have been mixed in human studies, which may be attributable to inter-individual differences in aerobic fitness and cognitive responses to aerobic exercise. This study evaluated inter-individual differences in aerobic fitness and cognitive responses to 6-month aerobic exercise in participants with AD dementia by secondarily analyzing the FIT-AD Trial data. Aerobic fitness with the shuttle walk test (SWT), 6-minute walk test (6MWT), and maximal oxygen consumption (VO2max) from cycle-ergometer exercise test, and cognition with the AD Assessment Scale–Cognition (ADAS-Cog). Inter-individual differences were calculated as the differences in the standard deviation of 6-month change (SDR) in outcomes between the intervention and control groups. The sample size was 78 (77.4±6.3 years old, 15.7±2.8 years of education, 41% women). VO2max was available in 26 participants (77.7±7.1 years old, 14.8±2.6 years of education, 35% women). The results show that the SDR was 37.0, 121.1, 1.7, and 2.3 for SWT, 6MWT, VO2max, and ADAS-Cog, respectively, but there were no statistically significant differences between the intervention and control groups in these measures over six months. Our results indicate that inter-individual differences exist in aerobic fitness and cognitive responses to aerobic exercise in AD, which contributed to the favorable, but not statistically significant between-group differences in aerobic fitness and cognition. To conclude, our study is the first to demonstrate inter-individual differences in the responses to aerobic exercise in AD dementia using SDR.

scholarly journals Association between increased levels of amyloid-β oligomers in plasma and episodic memory loss in Alzheimer’s disease

2019 ◽  
Vol 11 (1) ◽  
Author(s):  
Xue Meng ◽  
Tao Li ◽  
Xiao Wang ◽  
Xiaozhen Lv ◽  
Zhiyu Sun ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Episodic Memory ◽  
Cognitive Performance ◽  
Memory Performance ◽  
Amyloid Β ◽  
Disease Assessment ◽  
Control Groups ◽  
Delayed Recall ◽  
And Control

Abstract Objective The objectives of this study were to investigate whether the plasma levels of oligomeric amyloid-β (OAβ) were affected in Alzheimer’s disease (AD) and to examine the associations (or possible correlations) between plasma OAβ levels and memory performance. Method Thirty subjects with AD and 28 cognitively normal controls were recruited in the study. The multimer detection system (MDS) was used to measure the levels of OAβ in the plasma. In addition to assessing the general cognitive function with the Mini-Mental State Examination (MMSE), Cognitive Abilities Screening Instrument (CASI), and Alzheimer’s Disease Assessment Scale–cognitive portion (ADAS-Cog), the common objects memory test (COMT) was used to examine the episodic memory performance. Pearson’s and partial correlation analyses were conducted to explore the associations between cognitive performance and OAβ levels in the plasma. A receiving operating curve (ROC) analysis was used to discriminate between the AD and control groups. Results The plasma OAβ levels in the AD group were significantly higher than those in the control group [1.88 (0.38) ng/ml vs 1.20 (0.40) ng/ml, p < 0.001]. The elevated levels of plasma OAβ showed a strong correlation with cognitive performance in patients with AD, including an inverse correlation with scores on the MMSE (r = − 0.43, p = 0.02), CASI (r = − 0.56, p < 0.01), and the immediate recall (r = − 0.45, p = 0.01), 5-min delayed recall (r = − 0.56, p < 0.01), and 30-min delayed recall (r = − 0.71, p < 0.001) tests of the COMT, and a positive correlation with the ADAS-Cog scores (r = 0.59, p < 0.001). The EDTA plasma Aβ oligomer optical density (OD) value measured using the MDS could discriminate between the AD and control groups with an area under the curve (AUC) of 0.89. The optimal sensitivity and specificity were 82.1% and 90.0%, respectively. Conclusion The elevated levels of OAβ in the plasma distinguished the AD and control groups and were associated with the severity of symptoms, especially memory performance, in patients with AD. Our results suggested that plasma OAβ could potentially be a simple and non-invasive blood-based biomarker for AD diagnosis. Furthermore, longitudinal studies are warranted to explore the application of plasma OAβ levels as a valid diagnostic biomarker in patients with 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.

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