scholarly journals Investigating the Relationship between Diabetes and Alzheimer’s Disease:

2020 ◽  
Vol 7 (1) ◽  
pp. 1-11
Author(s):  
Tammanna R. Sahrawat ◽  
Jyoti Dwivedi
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
System Biology ◽  
Network System ◽  
System Biology Approach ◽  
Common Elements ◽  
Age Related ◽  
Potential Marker ◽  
The Common ◽  
The Relationship

Ageing is associated with a number of diseases. Alzheimer’s disease (AD) and diabetes are among such most common diseases. These two diseases are considered to be fundamentally similar disorders because they share some common elements, though they differ in the time of onset, tissues affected as well as the magnitudes of their specific traits. The present study was undertaken to prospect the association between the genes involved in Diabetes and AD; and their common pathophysiology. Using a network system biology approach, the genes common between Diabetes and AD were retrieved from DisGeNET database. The common genes were analysed using in silico tool, Cyctoscape’s various plug-ins, ClusterONE, CytoHubba, ClueGO and CluePedia. Eleven genes which can act as potential marker for both Diabetes and AD namely IL4, ICAM1, ALB, INS, CSF2, IL6, TNF, IL10, GAPDH, TLR4, and AKT have been identified in the present study. This is the first study of its kind in which relationship between Diabetes and AD has been investigated to identify their common genes, which can help in better understanding of pathophysiology of these age-related diseases.

scholarly journals Tau seeding activity anticipates phospho-tau pathology in Alzheimer’s disease

2018 ◽  
Author(s):  
Sarah K. Kaufman ◽  
Kelly Del Tredici ◽  
Talitha L. Thomas ◽  
Heiko Braak ◽  
Marc I. Diamond
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Visual Cortex ◽  
Brain Regions ◽  
Tau Pathology ◽  
Age Related ◽  
Important Addition ◽  
Disease Stages ◽  
Relationship Of ◽  
The Relationship

AbstractAlzheimer’s disease (AD) is characterized by accumulation of tau neurofibrillary tangles (NFTs) and, according to the prion model, transcellular propagation of pathological “seeds” may underlie its progression. Staging of NFT pathology with phospho-tau antibody is useful to classify AD and primary age-related tauopathy (PART) cases. The locus coeruleus (LC) shows the earliest phospho-tau signal, whereas other studies suggest that pathology begins in the transentorhinal/entorhinal cortices (TRE/EC). The relationship of tau seeding activity, phospho-tau pathology, and progression of neurodegeneration remains obscure. Consequently, we employed an established cellular biosensor assay to quantify tau seeding activity in fixed human tissue, in parallel with AT8 phospho-tau staining of immediately adjacent sections. We studied four brain regions from each of n=247 individuals across a range of disease stages. We detected the earliest and most robust seeding activity in the TRE/EC. The LC did not uniformly exhibit seeding activity until later NFT stages. We also detected seeding activity in the first temporal gyrus and visual cortex at stages before NFTs and/or AT8-immunopositivity were detectable. AD and putative PART cases exhibited similar patterns of seeding activity that anticipated histopathology across all NFT stages. Our findings are consistent with the prion model and suggest that pathological seeding activity begins in the TRE/EC rather than in the LC, and may offer an important addition to classical histopathology.

scholarly journals Cell type-specific potential pathogenic genes and functional pathways in Alzheimer’s Disease

BMC Neurology ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Xiao-Lan Wang ◽  
Lianjian Li
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Neurodegenerative Disorder ◽  
Single Cells ◽  
Estrogen Signaling ◽  
Cell Type ◽  
Age Related ◽  
Excitatory Neurons ◽  
Cell Type Specific ◽  
The Common

Abstract Background Alzheimer's disease (AD) is a pervasive age-related and highly heritable neurodegenerative disorder but has no effective therapy. The complex cellular microenvironment in the AD brain impedes our understanding of pathogenesis. Thus, a comprehensive investigation of cell type-specific responses in AD is crucial to provide precise molecular and cellular targets for therapeutic development. Methods Here, we integrated analyzed 4,441 differentially expressed genes (DEGs) that were identified from 263,370 single-cells in cortex samples by single-nucleus RNA sequencing (snRNA-seq) between 42 AD-pathology subjects and 39 normal controls within 3 studies. DEGs were analyzed in microglia, astrocytes, oligodendrocytes, excitatory neurons, inhibitory neurons, and endothelial cells, respectively. In each cell type, we identified both common DEGs which were observed in all 3 studies, and overlapping DEGs which have been seen in at least 2 studies. Firstly, we showed the common DEGs expression and explained the biological functions by comparing with existing literature or multil-omics signaling pathways knowledgebase. We then determined the significant modules and hub genes, and explored the biological processes using the overlapping DEGs. Finally, we identified the common and distinct dysregulated pathways using overall DEGs and overlapping DEGs in a cell type-specific manner. Results Up-regulated LINGO1 has been seen in both oligodendrocytes and excitatory neurons across 3 studies. Interestingly, genes enriched in the mitochondrial module were up-regulated across all cell types, which indicates mitochondrial dysfunction in the AD brain. The estrogen signaling pathway seems to be the most common pathway that is disrupted in AD. Conclusion Together, these analyses provide detailed information of cell type-specific and overall transcriptional changes and pathways underlying the human AD-pathology. These findings may provide important insights for drug development to tackle this disease.

scholarly journals 0422 Apocalypse Tau: The Relationship Between Inflammaging and Local Sleep Disruption in Older Adults is Mediated by Tau Burden

SLEEP ◽  
2020 ◽  
Vol 43 (Supplement_1) ◽  
pp. A161-A162
Author(s):  
A Dave ◽  
K E Sprecher ◽  
K K Lui ◽  
M G Chappel-Farley ◽  
I Y Chen ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Older Adults ◽  
Alzheimer's Disease ◽  
Chronic Inflammation ◽  
Glial Activation ◽  
Sleep Disruption ◽  
Age Related ◽  
The Relationship ◽  
Local Expression ◽  
Local Sleep

Abstract Introduction Chronic inflammation in aging is independently associated with tau burden and sleep disruption, though the mechanism linking inflammation with sleep disruption remains unknown. Recent evidence associates tau burden with deficits in local expression of sleep spindles and slow wave activity (SWA). Here we test the hypothesis that age-related central inflammation disrupts local sleep by influencing tau pathology. Methods Cognitively asymptomatic older adults from the Wisconsin Alzheimer’s Disease Research Center underwent overnight polysomnography with high-density electroencephalography (hdEEG; 256 channels) at the University of Wisconsin-Madison (n=33, 61.9±6.7 years, 23 female). EEG data were subjected to multitaper spectral analysis (0.5-40Hz) to yield topographic maps of SWA (SWA1:0.5-1Hz, SWA2:1-4.5Hz) and spindle (sigma1:11-13Hz; sigma2:13-16Hz) power during NREM sleep. Cerebrospinal fluid assay-based measurements of YKL-40 (indicating glial activation), phosphorylated tau (Ptau), and total tau (Ttau), were correlated with SWA and sigma topographical power employing Holm-Bonferroni correction. Multiple linear regression models were implemented controlling for age, apnea-hypopnea index (AHI), and sex at significant derivations. Finally, Sobel testing was employed to assess whether tau burden mediated YKL-40-sleep associations. Results Age was associated with YKL-40 (r=0.53, p=0.002), and YKL-40 was associated with both Ptau (r=0.66, p<0.001) and Ttau (r=0.68, p<0.001). Correlations between sigma2 activity and both Ptau and Ttau were detected at 14 derivations, 12 of which remained significant after controlling for age, sex, and AHI. YKL-40 was associated with sigma2 power (r=-0.39, p=0.025) across derivations expressing peak significance with tau. Sobel mediation analyses indicated that both Ptau (t=-2.15, p=0.031) and Ttau (t=-2.36, p=0.018) mediated the relationship between YKL-40 and sigma2 activity at these derivations. SWA was not associated with Ttau, Ptau, or YKL-40. Conclusion These results suggest that age-related increases in central glial activation may disrupt local expression of fast spindles by increasing tau burden, highlighting a potential role for chronic inflammation in sleep deficits observed in aging and Alzheimer’s disease. Support Supported by R56 AG052698, P50AG033514

scholarly journals Steroids and Alzheimer’s Disease: Changes Associated with Pathology and Therapeutic Potential

2020 ◽  
Vol 21 (13) ◽  
pp. 4812 ◽  
Author(s):  
Yvette Akwa
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Therapeutic Potential ◽  
Current Knowledge ◽  
Memory Loss ◽  
Amyloid Β ◽  
Neuroactive Steroids ◽  
Age Related ◽  
Pathogenic Factors ◽  
The Relationship

Alzheimer’s disease (AD) is a multifactorial age-related neurodegenerative disease that today has no effective treatment to prevent or slow its progression. Neuroactive steroids, including neurosteroids and sex steroids, have attracted attention as potential suitable candidates to alleviate AD pathology. Accumulating evidence shows that they exhibit pleiotropic neuroprotective properties that are relevant for AD. This review focuses on the relationship between selected neuroactive steroids and the main aspects of AD disease, pointing out contributions and gaps with reference to sex differences. We take into account the regulation of brain steroid concentrations associated with human AD pathology. Consideration is given to preclinical studies in AD models providing current knowledge on the neuroprotection offered by neuroactive (neuro)steroids on major AD pathogenic factors, such as amyloid-β (Aβ) and tau pathology, mitochondrial impairment, neuroinflammation, neurogenesis and memory loss. Stimulating endogenous steroid production opens a new steroid-based strategy to potentially overcome AD pathology. This article is part of a Special Issue entitled Steroids and the Nervous System.

MiR-335-5p Inhibits β-Amyloid (Aβ) Accumulation to Attenuate Cognitive Deficits Through Targeting c-jun-N-terminal Kinase 3 in Alzheimer’s Disease

2020 ◽  
Vol 17 (1) ◽  
pp. 93-101 ◽  
Author(s):  
Dan Wang ◽  
Zhifu Fei ◽  
Song Luo ◽  
Hai Wang
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Transgenic Mice ◽  
Western Blot ◽  
Mrna Expression ◽  
Cognitive Deficits ◽  
Protein Levels ◽  
Amyloid Aβ ◽  
Β Amyloid ◽  
The Relationship

Objectives: Alzheimer's disease (AD), also known as senile dementia, is a common neurodegenerative disease characterized by progressive cognitive impairment and personality changes. Numerous evidences have suggested that microRNAs (miRNAs) are involved in the pathogenesis and development of AD. However, the exact role of miR-335-5p in the progression of AD is still not clearly clarified. Methods: The protein and mRNA levels were measured by western blot and RNA extraction and quantitative real-time PCR (qRT-PCR), respectively. The relationship between miR-335-5p and c-jun-N-terminal kinase 3 (JNK3) was confirmed by dual-luciferase reporter assay. SH-SY5Y cells were transfected with APP mutant gene to establish the in vitro AD cell model. Flow cytometry and western blot were performed to evaluate cell apoptosis. The APP/PS1 transgenic mice were used as an in vivo AD model. Morris water maze test was performed to assess the effect of miR- 335-5p on the cognitive deficits in APP/PS1 transgenic mice. Results: The JNK3 mRNA expression and protein levels of JNK3 and β-Amyloid (Aβ) were significantly up-regulated, and the mRNA expression of miR-335-5p was down-regulated in the brain tissues of AD patients. The expression levels of miR-335-5p and JNK3 were significantly inversely correlated. Further, the dual Luciferase assay verified the relationship between miR-335- 5p and JNK3. Overexpression of miR-335-5p significantly decreased the protein levels of JNK3 and Aβ and inhibited apoptosis in SH-SY5Y/APPswe cells, whereas the inhibition of miR-335-5p obtained the opposite results. Moreover, the overexpression of miR-335-5p remarkably improved the cognitive abilities of APP/PS1 mice. Conclusion: The results revealed that the increased JNK3 expression, negatively regulated by miR-335-5p, may be a potential mechanism that contributes to Aβ accumulation and AD progression, indicating a novel approach for AD treatment.

A Biomarker Combining Imaging and Neuropsychological Assessment for Tracking Early Alzheimer's Disease in Clinical Trials

2018 ◽  
Vol 15 (5) ◽  
pp. 429-442 ◽  
Author(s):  
Nishant Verma ◽  
S. Natasha Beretvas ◽  
Belen Pascual ◽  
Joseph C. Masdeu ◽  
Mia K. Markey ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Clinical Trials ◽  
Cognitive Impairment ◽  
Latent Variable ◽  
Brain Regions ◽  
Disease Assessment ◽  
Latent Variable Analysis ◽  
The Relationship ◽  
Selection Of

Background: Combining optimized cognitive (Alzheimer's Disease Assessment Scale- Cognitive subscale, ADAS-Cog) and atrophy markers of Alzheimer's disease for tracking progression in clinical trials may provide greater sensitivity than currently used methods, which have yielded negative results in multiple recent trials. Furthermore, it is critical to clarify the relationship among the subcomponents yielded by cognitive and imaging testing, to address the symptomatic and anatomical variability of Alzheimer's disease. Method: Using latent variable analysis, we thoroughly investigated the relationship between cognitive impairment, as assessed on the ADAS-Cog, and cerebral atrophy. A biomarker was developed for Alzheimer's clinical trials that combines cognitive and atrophy markers. Results: Atrophy within specific brain regions was found to be closely related with impairment in cognitive domains of memory, language, and praxis. The proposed biomarker showed significantly better sensitivity in tracking progression of cognitive impairment than the ADAS-Cog in simulated trials and a real world problem. The biomarker also improved the selection of MCI patients (78.8±4.9% specificity at 80% sensitivity) that will evolve to Alzheimer's disease for clinical trials. Conclusion: The proposed biomarker provides a boost to the efficacy of clinical trials focused in the mild cognitive impairment (MCI) stage by significantly improving the sensitivity to detect treatment effects and improving the selection of MCI patients that will evolve to Alzheimer’s disease.

Emerging Promise of Immunotherapy for Alzheimer’s Disease: A New Hope for the Development of Alzheimer’s Vaccine

2020 ◽  
Vol 20 (13) ◽  
pp. 1214-1234 ◽  
Author(s):  
Md. Tanvir Kabir ◽  
Md. Sahab Uddin ◽  
Bijo Mathew ◽  
Pankoj Kumar Das ◽  
Asma Perveen ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Immune Response ◽  
Neutralizing Antibodies ◽  
Neurodegenerative Disorder ◽  
Symptomatic Relief ◽  
Aβ Oligomers ◽  
Th2 Immune Response ◽  
Age Related ◽  
Anti Inflammatory

Background: Alzheimer's disease (AD) is a chronic neurodegenerative disorder and the characteristics of this devastating disorder include the progressive and disabling deficits in the cognitive functions including reasoning, attention, judgment, comprehension, memory, and language. Objective: In this article, we have focused on the recent progress that has been achieved in the development of an effective AD vaccine. Summary: Currently, available treatment options of AD are limited to deliver short-term symptomatic relief only. A number of strategies targeting amyloid-beta (Aβ) have been developed in order to treat or prevent AD. In order to exert an effective immune response, an AD vaccine should contain adjuvants that can induce an effective anti-inflammatory T helper 2 (Th2) immune response. AD vaccines should also possess the immunogens which have the capacity to stimulate a protective immune response against various cytotoxic Aβ conformers. The induction of an effective vaccine’s immune response would necessitate the parallel delivery of immunogen to dendritic cells (DCs) and their priming to stimulate a Th2-polarized response. The aforesaid immune response is likely to mediate the generation of neutralizing antibodies against the neurotoxic Aβ oligomers (AβOs) and also anti-inflammatory cytokines, thus preventing the AD-related inflammation. Conclusion: Since there is an age-related decline in the immune functions, therefore vaccines are more likely to prevent AD instead of providing treatment. AD vaccines might be an effective and convenient approach to avoid the treatment-related huge expense.

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