Genetic underpinnings in Alzheimer’s disease – a review

Moustafa, Ahmed A.; Hassan, Mubashir; Hewedi, Doaa H.; Hewedi, Iman H.; Garami, Julia; Ashwal, Hany Al; Zaki, Nazar; Seo, Sung‐Yum; Cutsuridis, Vassilis; Angulo, Sergio; Natesh, Joman Y.; Herzallah, Mohammad M.; Frydecka, Dorota; Misiak, Błażej; Salama, Mohamed; Mohamed, Wael; Haj, Mohamad El; Hornberger, Michael

doi:10.1515/revneuro-2017-0036

Cited by 34 publications

(12 citation statements)

References 149 publications

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“…In contrast, most AD patients have late-onset symptoms of dementia with undefined causes. Recent results from genome wide association studies (GWAS) provide several genes that associated with AD (Lambert et al, 2013; Moustafa et al, 2018; Van Cauwenberghe et al, 2016); however, the mechanisms between these genes and AD pathophysiology remain to be elucidated.…”

Section: Alzheimer's Disease (Ad)mentioning

confidence: 99%

Sleep and circadian rhythm disruption and stress intersect in Alzheimer's disease

Phan

Malkani

2019

Neurobiology of Stress

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Alzheimer's disease (AD) was discovered and the pathological hallmarks were revealed more than a century ago. Subsequently, many remarkable discoveries and breakthroughs provided us with mechanistic insights into the pathogenesis of AD. The identification of the molecular underpinning of the disease not only provided the framework of AD pathogenesis but also targets for therapeutic inventions. Despite all the initial successes, no effective treatment for AD has emerged yet as all the late stages of clinical trials have failed. Many factors ranging from genetic to environmental factors have been critically appraised as the potential causes of AD. In particular, the role of stress on AD has been intensively studied while the relationship between sleep and circadian rhythm disruption (SCRD) and AD have recently emerged. SCRD has always been thought to be a corollary of AD pathologies until recently, multiple lines of evidence converge on the notion that SCRD might be a contributing factor in AD pathogenesis. More importantly, how stress and SCRD intersect and make their concerted contributions to AD phenotypes has not been reviewed. The goal of this literature review is to examine at multiple levels – molecular, cellular (e.g. microglia, gut microbiota) and holistic – how the interaction between stress and SCRD bi-directionally and synergistically exacerbate AD pathologies and cognitive impairment. AD, in turn, worsens stress and SCRD and forms the vicious cycle that perpetuates and amplifies AD.

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Section: Alzheimer's Disease (Ad)mentioning

confidence: 99%

Sleep and circadian rhythm disruption and stress intersect in Alzheimer's disease

Phan

Malkani

2019

Neurobiology of Stress

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“…The three main causative genes ( APP, PSEN1 , and PSEN2 ) and one common genetic risk factor ( APOEε4 allele) have been identified. Large-scale GWAS studies found multiple additional risk loci for late-onset AD, with the associated genes mapping to the three principal pathways: cholesterol and lipid metabolism; immune system and inflammatory response; and endosomal vesicle cycling [ 132 ].…”

Section: Neat1/paraspeckles Are Dysregulated In Neurodegenerative Dismentioning

confidence: 99%

NEAT1 and paraspeckles in neurodegenerative diseases: A missing lnc found?

Williams

Shelkovnikova

2018

Non-coding RNA Research

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Neurodegenerative diseases are among the most common causes of disability worldwide. Although neurodegenerative diseases are heterogeneous in both their clinical features and the underlying physiology, they are all characterised by progressive loss of specific neuronal populations. Recent experimental evidence suggests that long non-coding RNAs (lncRNAs) play important roles in the CNS in health and disease. Nuclear Paraspeckle Assembly Transcript 1 (NEAT1) is an abundant, ubiquitously expressed lncRNA, which forms a scaffold for a specific RNA granule in the nucleus, or nuclear body, the paraspeckle. Paraspeckles act as molecular hubs for cellular processes commonly affected by neurodegeneration. Transcriptomic analyses of the diseased human tissue have revealed altered NEAT1 levels in the CNS in major neurodegenerative disorders as well as in some disease models. Although it is clear that changes in NEAT1 expression (and in some cases, paraspeckle assembly) accompany neuronal damage, our understanding of NEAT1 contribution to the disease pathogenesis is still rudimentary. In this review, we have summarised the available knowledge on NEAT1 involvement in the molecular processes linked to neurodegeneration and on NEAT1 dysregulation in this type of disease, with a special focus on amyotrophic lateral sclerosis. The goal of this review is to attract the attention of researchers in the field of neurodegeneration to NEAT1 and paraspeckles.

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“…In previous work a lot of genes belonging to C 1 and C 2 communities had already been highlighted as linked to AD. For example RIN3 was found to play key roles in the development of AD ad in particular it resulted associated with AD risk [58, 59]. J.W.…”

Section: Resultsmentioning

confidence: 99%

Shannon entropy approach reveals relevant genes in Alzheimer’s disease

et al. 2019

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Alzheimer’s disease (AD) is the most common type of dementia and affects millions of people worldwide. Since complex diseases are often the result of combinations of gene interactions, microarray data and gene co-expression analysis can provide tools for addressing complexity. Our study aimed to find groups of interacting genes that are relevant in the development of AD. In this perspective, we implemented a method proposed in a previous work to detect gene communities linked to AD. Our strategy combined co-expression network analysis with the study of Shannon entropy of the betweenness. We analyzed the publicly available GSE1297 dataset, achieved from the GEO database in NCBI, containing hippocampal gene expression of 9 control and 22 AD human subjects. Co-expressed genes were clustered into different communities. Two communities of interest (composed by 72 and 39 genes) were found by calculating the correlation coefficient between communities and clinical features. The detected communities resulted stable, replicated on two independent datasets and mostly enriched in pathways closely associated with neuro-degenative diseases. A comparison between our findings and other module detection techniques showed that the detected communities were more related to AD phenotype. Lastly, the hub genes within the two communities of interest were identified by means of a centrality analysis and a bootstrap procedure. The communities of the hub genes presented even stronger correlation with clinical features. These findings and further explorations on the detected genes could shed light on the genetic aspects related with physiological aspects of Alzheimer’s disease.

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Genetic underpinnings in Alzheimer’s disease – a review

Cited by 34 publications

References 149 publications

Sleep and circadian rhythm disruption and stress intersect in Alzheimer's disease

Sleep and circadian rhythm disruption and stress intersect in Alzheimer's disease

NEAT1 and paraspeckles in neurodegenerative diseases: A missing lnc found?

Shannon entropy approach reveals relevant genes in Alzheimer’s disease

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