scholarly journals ABCA1-Labeled Exosomes in Serum Contain Higher MicroRNA-193b Levels in Alzheimer’s Disease

2021 ◽  
Vol 2021 ◽  
pp. 1-10
Author(s):  
Chen-Geng Liu ◽  
Yue Zhao ◽  
Yao Lu ◽  
Pei-Chang Wang

Objective. We aimed to establish a method to determine whether microRNA-193b (miR-193b) levels in ABCA1-labeled serum exosomes might serve as a marker for the diagnosis of Alzheimer’s disease. Methods. We used immunocapture methods to determine the levels of ABCA1-labeled exosomal miR-193b in cultures of white blood cells (WBCs), red blood cells (RBCs), mouse hippocampal neuron HT-22 cells, and primary mouse neuronal cells. ABCA1-labeled exosomal miR-193b levels were also evaluated in the cerebrospinal fluid (CSF) and serum of APP/PS1 double-transgenic mice, as well as control subjects ( n = 60 ) and study participants with subjective cognitive decline (SCD, n = 89 ), stage and mild cognitive impairment (MCI, n = 92 ), and dementia of the Alzheimer type (DAT, n = 92 ). Results. ABCA1 levels of exosomes harvested from the medium of HT-22 cells and neurons were significantly higher than those of RBCs and WBCs ( P < 0.05 ). Exosomal ABCA1 from the CSF of APP/PS1 mice were transmitted to the serum of wild-type mice after injection, and high miR-193b levels were observed in both the serum and CSF after injection. The ABCA1-labeled exosomal miR-193b levels were higher in the CSF of MCI and DAT patients compared with the CSF of the control group ( P < 0.05 ). The ABCA1-labeled exosomal miR-193b were also slightly higher ( P > 0.05 ) in the serum of SCD patients and significantly higher in the serum of MCI and DAT patients compared with the serum of the control group ( P < 0.05 ). Conclusion. This study provides a method to capture specific exosomes. Detection of serum exosomes labeled with ABCA1 may facilitate the early diagnosis of AD.

2020 ◽  
Author(s):  
Marta González-Sánchez ◽  
Fernando Bartolome ◽  
Desiree Antequera ◽  
Veronica Puertas-Martín ◽  
Pilar González ◽  
...  

Abstract Background Efforts focused on developing new less invasive biomarkers for early Alzheimer’s disease (AD) diagnosis are substantial. Evidences of infectious pathogens in AD brains may suggest a deteriorated innate immune system in AD pathophysiology. We previously demonstrated reduced salivary levels of Lf in AD patients, one of the major antimicrobial peptides. Methods To assess the clinical utility of salivary Lf for AD diagnosis, we examine the relationship between salivary Lf and cerebral amyloid-β (Aβ) load in two different cross-sectional cohorts including patients with different neurodegenerative disorders. Study participants for cohort 1 (n = 116) were enrolled from the 12 de Octubre University Hospital Neurology Service in Madrid (Spain) and Pablo de Olavide University in Sevilla (Spain). Study participants for cohort 2 (n = 142) were enrolled as part of the Atherobrain - Heart to Head (H2H) project. Participants underwent neurological and neuropsychological examination, saliva sampling, and amyloid-Positron-Emission Tomography (PET) neuroimaging. Results The diagnostic performance of salivary Lf in the cohort 1 had an area under the curve [AUC] of 0.95 (0.911-0.992) for the differentiation of the prodromal AD/AD group positive for amyloid-PET (PET + ) versus healthy group, and 0.97 (0.924-1) versus the frontotemporal dementia (FTD) group. In the cohort 2, salivary Lf had also an excellent diagnostic performance in the health control group versus prodromal AD comparison: AUC 0.93 (95% CI 0.876-0.989). Salivary Lf detected prodromal AD and AD dementia distinguishing them from other dementias as FTD with over 87% sensitivity and 91% specificity. Conclusion Therefore, salivary Lf seems to have a very good diagnostic performance to detect AD. Our findings support the possible utility of salivary Lf as a new non-invasive and cost-effective AD biomarker.


Synapse ◽  
2013 ◽  
Vol 67 (8) ◽  
pp. 541-543 ◽  
Author(s):  
Kaneez Fatima Shad ◽  
Yashar Aghazadeh ◽  
Sagheer Ahmad ◽  
Bodo Kress

2020 ◽  
Author(s):  
Hao Hu ◽  
Lan Tan ◽  
Yan-Lin Bi ◽  
Wei Xu ◽  
Lin Tan ◽  
...  

Abstract Background The preclinical stage of Alzheimer's disease (AD) has become a key target stage for future AD prevention trials. Serum apolipoprotein, an important lipid-related factor, has been found to be involved in the pathogenesis of AD. This study was to examine whether apolipoprotein B (ApoB), apolipoprotein A-1 (ApoA1) or the ratio of ApoB and ApoA1 (ApoB/A1) were associated with early changes of cerebrospinal fluid (CSF) AD biomarkers in elderly adults with subjective cognitive decline. Methods This study included 201 cognitive normal (CN) elderly adults and 101 participants with subjective cognitive decline (SCD) from the Chinese Alzheimer’s Biomarker and LifestylE (CABLE) database. The Kruskall-Wallis test and Chisquare test were applied in the intergroup comparisons. Multiple linear regression models were used to examine the cross-sectional associations of serum ApoB, ApoA1 and ApoB/A1 levels with CSF AD-related biomarkers. Results Compared with the control group, SCD participants with significant AD biological characteristics had lower ApoB levels. In the total participants, higher level of serum ApoB was associated with increases in CSF Aβ42 (p = 0.0009) and Aβ42/40 (p = 0.0038) as well as decreases in CSF t-tau/Aβ42 (p < 0.0001) and p-tau/Aβ42 (p < 0.0001), independent of APOEɛ4 status. In the further subgroup analysis, these associations were much more significant in the SCD participants. In addition, higher levels of serum ApoB were also found associated with decreases in CSF t-tau (p = 0.0224), p-tau (p = 0.0086) and Aβ40 (p = 0.0297) in the SCD subgroup. Furthermore, we found that these protective associations between serum ApoB and CSF AD core biomarkers were much more significant in the overweight participants. Results showed no association between ApoA1 and all CSF biomarkers in either total participants or subgroups. Conclusions This study is the first to find protective associations of serum ApoB, but not ApoA1, with CSF AD core biomarkers in elderly adults, and these associations were more significant in SCD individuals. This finding indicated that ApoB may play a protective role in the preclinical stage of AD. Identifying the underlying mechanisms may contribute to the discovery of new pathogenic mechanisms and therapeutic targets.


1999 ◽  
Vol 11 (4) ◽  
pp. 227-231 ◽  
Author(s):  
T. Vecchi ◽  
V. Saveriano ◽  
L. Paciaroni

A selective deterioration of working memory functions has been suggested as an explanation of the cognitive decay occurring in normal ageing as well as in Alzheimer-type dementia. Recent studies have highlighted that elderly people’s limitations in working memory functions may be better interpreted when analysing the specific characteristics of the cognitive process (i.e., passive storage or active manipulation of information). In the present study, we have adapted a procedure used to investigate age-related memory modifications, involving both verbal and visuo-spatial material in tasks tapping passive and active processes, to investigate the deterioration associated with Alzheimer's disease. A group of Alzheimer patients in the early stages of the disease were matched to a control group of healthy elderly. Results show that Alzheimer patients performed less accurately than the control group in all tasks. However, the deficit was maximised in the case of active processes, regardless of the type of material used (verbal or visuo-spatial). These data highlight the importance of considering the amount of active processing as the key variable when interpreting the decay in cognitive functions in the early stages of Alzheimer’s disease.


2020 ◽  
Author(s):  
Hao Hu ◽  
Lan Tan ◽  
Yan-Lin Bi ◽  
Wei Xu ◽  
Lin Tan ◽  
...  

Abstract Background: The preclinical stage of Alzheimer's disease (AD) has become a key target stage for future AD prevention trials. Serum apolipoprotein, an important lipid-related factor, has been found to be involved in the pathogenesis of AD. This study was to examine whether apolipoprotein B (ApoB), apolipoprotein A-1 (ApoA1) or the ratio of ApoB and ApoA1 (ApoB/A1) were associated with early changes of cerebrospinal fluid (CSF) AD biomarkers in elderly adults with subjective cognitive decline.Methods: This study included 201 cognitive normal (CN) elderly adults and 101 participants with subjective cognitive decline (SCD) from the Chinese Alzheimer’s Biomarker and LifestylE (CABLE) database. The Kruskall-Wallis test and Chisquare test were applied in the intergroup comparisons. Multiple linear regression models were used to examine the cross-sectional associations of serum ApoB, ApoA1 and ApoB/A1 levels with CSF AD-related biomarkers.Results: Compared with the control group, SCD participants with significant AD biological characteristics had lower ApoB levels. In the total participants, higher level of serum ApoB was associated with increases in CSF Aβ42 (p = 0.0009) and Aβ42/40 (p = 0.0038) as well as decreases in CSF t-tau/Aβ42 (p < 0.0001) and p-tau/Aβ42 (p < 0.0001), independent of APOEɛ4 status. In the further subgroup analysis, these associations were much more significant in the SCD participants. In addition, higher levels of serum ApoB were also found associated with decreases in CSF t-tau (p = 0.0224), p-tau (p = 0.0086) and Aβ40 (p = 0.0297) in the SCD subgroup. Furthermore, we found that these protective associations between serum ApoB and CSF AD core biomarkers were much more significant in the overweight participants. Results showed no association between ApoA1 and all CSF biomarkers in either total participants or subgroups. Conclusions: This study is the first to find protective associations of serum ApoB, but not ApoA1, with CSF AD core biomarkers in elderly adults, and these associations were more significant in SCD individuals. This finding indicated that ApoB may play a protective role in the preclinical stage of AD. Identifying the underlying mechanisms may contribute to the discovery of new pathogenic mechanisms and therapeutic targets.


2017 ◽  
Vol 41 (S1) ◽  
pp. S655-S655
Author(s):  
T. Kalelioglu ◽  
M. Yuruyen ◽  
G. Gultekin ◽  
H. Yavuzer ◽  
Y. Ozturk ◽  
...  

BackgroundIn this study we aimed to explore the role of inflammation in subjects with mild Alzheimer dementia (AD), mild cognitive impairment (MCI) and subjective cognitive decline (SCD) via new potential inflammation markers of Neutrophil-lymphocyte ratio (NLR) and Platelet-lymphocyte ratio (PLR). NLR and PLR are useful and cost-effective biomarkers, showing peripheral systemic inflammation, were previously shown in neuropsychiatric disorders [1].MethodsIn screening phase the patients were assessed with mini-mental state examination, clinical dementia rating scale (CDR), geriatric depression scale (GDS) and Hachinski Ischemic Scale (HIS) after unstructured psychiatric interview according to diagnostic and statistical manual of mental disorder, Text Revised (DSM-IV, TR). Spectrum of cognitive decline includes 31 patients with mild Alzheimer's disease, 30 subjects with mild cognitive impairment, 31 individuals with subjective cognitive decline. Thirty-one healthy controls enrolled to the study.ResultsNLR value of patients with AD was 2.38 ± 0.81, subjects with MCI was 2.48 ± 1.19, SCD group was 2.24 ± 1.11 and control group was 1.85 ± 0.80. NLR was significantly higher in AD and MCI groups when compared with control group (P = 0.006, P = 0.03, respectively). Platelet-lymphocyte ratio was not correlated with cognitive impairment. Neutrophil counts were indifferent when comparing either of groups. Lymphocyte levels were significantly lower in each of cognitive decline groups when compared to healthy controls.ConclusionThe present findings suggest that systemic inflammation may have a role in developing Alzheimer's Disease.Disclosure of interestThe authors have not supplied their declaration of competing interest.


2019 ◽  
Vol 16 (9) ◽  
pp. 834-835
Author(s):  
Petter Järemo ◽  
Alenka Jejcic ◽  
Vesna Jelic ◽  
Tasmin Shahnaz ◽  
Homira Behbahani ◽  
...  

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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