scholarly journals Mitochondrial Alterations in Peripheral Mononuclear Blood Cells from Alzheimer’s Disease and Mild Cognitive Impairment Patients

2016 ◽  
Vol 2016 ◽  
pp. 1-11 ◽  
Author(s):  
A. Delbarba ◽  
G. Abate ◽  
C. Prandelli ◽  
M. Marziano ◽  
L. Buizza ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Mitochondrial Dna ◽  
Cognitive Impairment ◽  
Mild Cognitive Impairment ◽  
Cytochrome C ◽  
Blood Cells ◽  
Healthy Subjects ◽  
Mononuclear Cells ◽  
Mitochondrial Dna Copy Number

It is well recognized that mitochondrial dysfunction contributes to neurodegeneration occurring in Alzheimer’s disease (AD). However, evidences of mitochondrial defects in AD peripheral cells are still inconclusive. Here, some mitochondrial-encoded and nuclear-encoded proteins, involved in maintaining the correct mitochondria machine, were investigated in terms of protein expression and enzymatic activity in peripheral blood mononuclear cells (PBMCs) isolated from AD and Mild Cognitive Impairment (MCI) patients and healthy subjects. In addition mitochondrial DNA copy number was measured by real time PCR. We found some differences and some similarities between AD and MCI patients when compared with healthy subjects. For example, cytochrome C and cytochrome B were decreased in AD, while MCI showed only a statistical reduction of cytochrome C. On the other hand, both AD and MCI blood cells exhibited highly nitrated MnSOD, index of a prooxidant environment inside the mitochondria. TFAM, a regulator of mitochondrial genome replication and transcription, was decreased in both AD and MCI patients’ blood cells. Moreover also the mitochondrial DNA amount was reduced in PBMCs from both patient groups. In conclusion these data confirmed peripheral mitochondria impairment in AD and demonstrated that TFAM and mtDNA amount reduction could be two features of early events occurring in AD pathogenesis.

DEF8 and Autophagy-Associated Genes are Altered in Mild Cognitive Impairment, Probable Alzheimer’s Disease Patients and a Transgenic Model of the Disease

2021 ◽  
pp. 1-16
Author(s):  
Esteban Leyton ◽  
Diego Matus ◽  
Sandra Espinoza ◽  
José Matías Benitez ◽  
Bastián I. Cortes ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cognitive Impairment ◽  
Mild Cognitive Impairment ◽  
Real Time ◽  
Real Time Pcr ◽  
Mononuclear Cells ◽  
Differentially Expressed ◽  
Protein Levels ◽  
5Xfad Mice

Background: Disturbances in the autophagy/endolysosomal systems are proposed as early signatures of Alzheimer’s disease (AD). However, few studies are available concerning autophagy gene expression in AD patients. Objective: To explore the differential expression of classical genes involved in the autophagy pathway, among them a less characterized one, DEF8 (Differentially expressed in FDCP 8), initially considered a Rubicon family member, in peripheral blood mononuclear cells (PBMCs) from individuals with mild cognitive impairment (MCI) and probable AD (pAD) and correlate the results with the expression of DEF8 in the brain of 5xFAD mice. Method: By real-time PCR and flow cytometry, we evaluated autophagy genes levels in PBMCs from MCI and pAD patients. We evaluated DEF8 levels and its localization in brain samples of the 5xFAD mice by real-time PCR, western blot, and immunofluorescence. Results: Transcriptional levels of DEF8 were significantly reduced in PBMCs of MCI and pAD patients compared with healthy donors, correlating with the MoCA and MoCA-MIS cognitive tests scores. DEF8 protein levels were increased in lymphocytes from MCI but not pAD, compared to controls. In the case of brain samples from 5xFAD mice, we observed a reduced mRNA expression and augmented protein levels in 5xFAD compared to age-matched wild-type mice. DEF8 presented a neuronal localization. Conclusion: DEF8, a protein proposed to act at the final step of the autophagy/endolysosomal pathway, is differentially expressed in PBMCs of MCI and pAD and neurons of 5xFAD mice. These results suggest a potential role for DEF8 in the pathophysiology of AD.

scholarly journals Assessment of Functional Characteristics of Amnestic Mild Cognitive Impairment and Alzheimer’s Disease Using Various Methods of Resting-State FMRI Analysis

2015 ◽  
Vol 2015 ◽  
pp. 1-12 ◽  
Author(s):  
Jungho Cha ◽  
Jung-Min Hwang ◽  
Hang Joon Jo ◽  
Sang Won Seo ◽  
Duk L. Na ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cognitive Impairment ◽  
Mild Cognitive Impairment ◽  
Resting State ◽  
Healthy Subjects ◽  
Meta Analysis ◽  
Amnestic Mild Cognitive Impairment ◽  
Published Data ◽  
Functional Characteristics

Resting-state functional magnetic resonance imaging (RS FMRI) has been widely used to analyze functional alterations in amnestic mild cognitive impairment (aMCI) and Alzheimer’s disease (AD) patients. Although many clinical studies of aMCI and AD patients using RS FMRI have been undertaken, conducting a meta-analysis has not been easy because of seed selection bias by the investigators. The purpose of our study was to investigate the functional differences in aMCI and AD patients compared with healthy subjects in a meta-analysis. Thus, a multimethod approach using regional homogeneity, amplitude of low-frequency fluctuation (ALFF), fractional ALFF (fALFF), and global brain connectivity was used to investigate differences between three groups based on previously published data. According to the choice of RS FMRI approach used, the patterns of functional alteration were slightly different. Nevertheless, patients with aMCI and AD displayed consistently decreased functional characteristics with all approaches. All approaches showed that the functional characteristics in the left parahippocampal gyrus were decreased in AD patients compared with healthy subjects. Although some regions were slightly different according to the different RS FMRI approaches, patients with aMCI and AD showed a consistent pattern of decreased functional characteristics with all approaches.

scholarly journals Altered Redox State in Whole Blood Cells from Patients with Mild Cognitive Impairment and Alzheimer’s Disease

2019 ◽  
Vol 71 (1) ◽  
pp. 153-163 ◽  
Author(s):  
Irene Martínez de Toda ◽  
Lara Miguélez ◽  
Carmen Vida ◽  
Eva Carro ◽  
Mónica De la Fuente
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cognitive Impairment ◽  
Mild Cognitive Impairment ◽  
Whole Blood ◽  
Blood Cells ◽  
Redox State ◽  
Whole Blood Cells

ADAM10 gene expression in the blood cells of Alzheimer's disease patients and mild cognitive impairment subjects

Biomarkers ◽  
2015 ◽  
Vol 20 (3) ◽  
pp. 196-201 ◽  
Author(s):  
Patricia Regina Manzine ◽  
Elena Marcello ◽  
Barbara Borroni ◽  
Willem Kamphuis ◽  
Elly Hol ◽  
...  
Keyword(s):  
Gene Expression ◽  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cognitive Impairment ◽  
Mild Cognitive Impairment ◽  
Blood Cells

scholarly journals Systemic inflammasome activation and pyroptosis associate with the progression of amnestic mild cognitive impairment and Alzheimer’s disease

2021 ◽  
Vol 18 (1) ◽  
Author(s):  
Wenjuan Rui ◽  
Hong Xiao ◽  
Yi Fan ◽  
Zhongxuan Ma ◽  
Ming Xiao ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cognitive Impairment ◽  
Mild Cognitive Impairment ◽  
Cognitive Assessment ◽  
Mononuclear Cells ◽  
Quantitative Polymerase Chain Reaction ◽  
Amnestic Mild Cognitive Impairment ◽  
Enzyme Linked Immunosorbent Assay ◽  
Inflammasome Activation

Abstract Background Growing evidence indicates that inflammasome-mediated inflammation plays important roles in the pathophysiology of amnestic mild cognitive impairment (aMCI) and Alzheimer’s disease (AD). Pyroptosis induced by inflammasome, and Gasdermin D (GSDMD) is involved in several neurodegenerative disorders. However, it is not clear whether peripheral inflammasome and pyroptosis are activated in aMCI and AD patients, influencing on neuroinflammation. The aim of this study was to examine the association between systemic inflammasome-induced pyroptosis and clinical features in aMCI and AD. Methods A total of 86 participants, including 33 subjects with aMCI, 33 subjects with AD, and 20 cognitively normal controls, in this study. The Mini Mental State Examination (MMSE) and the Montreal Cognitive Assessment (MoCA) scale were used for cognitive assessment. Levels of inflammasome-related genes/proteins in peripheral blood mononuclear cells (PBMCs) were determined using quantitative polymerase chain reaction and Western blotting. The levels of IL-1β, Aβ1-42, Aβ1-40, p-tau, and t-tau in cerebrospinal fluid (CSF), as well as the plasma IL-1β level, were measured by enzyme-linked immunosorbent assay. Finally, lipopolysaccharides (LPS) were used to investigate the effects of systemic inflammasome-induced pyroptosis in an AD mice model. Results Several genes involved in the inflammatory response were enriched in PBMCs of AD patients. The mRNA and protein levels of NLRP3, caspase-1, GSDMD, and IL-1β were increased in PBMCs of aMCI and AD patients. The IL-1β level in plasma and CSF of aMCI and AD patients was significantly higher than that in controls and negatively correlated with the CSF Aβ1-42 level, as well as MMSE and MoCA scores. Furthermore, there was a positive correlation between the IL-1β level in plasma and CSF of aMCI or AD patients. In vivo experiments showed that systemic inflammasome-induced pyroptosis aggravated neuroinflammation in 5 × FAD mice. Conclusions Our findings showed that canonical inflammasome signaling and GSDMD-induced pyroptosis were activated in PBMCs of aMCI and AD patients. In addition, the proinflammatory cytokine IL-1β was strongly associated with the pathophysiology of aMCI and AD. As such, targeting inflammasome-induced pyroptosis may be a new approach to inhibit neuroinflammation in aMCI and AD patients.

Increased expression of Interleukin-18 receptor in blood cells of subjects with Mild Cognitive Impairment and Alzheimer’s disease

Cytokine ◽  
2013 ◽  
Vol 61 (2) ◽  
pp. 360-363 ◽  
Author(s):  
Francesca Salani ◽  
Antonio Ciaramella ◽  
Federica Bizzoni ◽  
Francesca Assogna ◽  
Carlo Caltagirone ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cognitive Impairment ◽  
Mild Cognitive Impairment ◽  
Blood Cells ◽  
Interleukin 18
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