Key Disease Mechanisms Linked to Alzheimer’s Disease in the Entorhinal Cortex

Bottero, Virginie; Powers, Dallen; Yalamanchi, Ashna; Quinn, James P.; Potashkin, Judith A.

doi:10.3390/ijms22083915

Cited by 24 publications

(27 citation statements)

References 133 publications

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“…However, further studies are needed to evaluate this association. Interestingly, previous analysis of DEGs between the entorhinal cortex of AD patients and healthy controls also showed alteration of the retrograde endocannabinoid signaling pathway and predicted GATA1 and GATA2 as the upstream regulators of the identified DEGs in AD [74]. Our results here identified altered pathways in each brain region of AD patients and shared pathways between AD sensitive brain regions.…”

Section: Discussionsupporting

confidence: 70%

Key Genes and Biochemical Networks in Various Brain Regions Affected in Alzheimer’s Disease

Abyadeh

Tofigh

Hosseinian

et al. 2022

Cells

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Alzheimer’s disease (AD) is one of the most complicated progressive neurodegenerative brain disorders, affecting millions of people around the world. Ageing remains one of the strongest risk factors associated with the disease and the increasing trend of the ageing population globally has significantly increased the pressure on healthcare systems worldwide. The pathogenesis of AD is being extensively investigated, yet several unknown key components remain. Therefore, we aimed to extract new knowledge from existing data. Ten gene expression datasets from different brain regions including the hippocampus, cerebellum, entorhinal, frontal and temporal cortices of 820 AD cases and 626 healthy controls were analyzed using the robust rank aggregation (RRA) method. Our results returned 1713 robust differentially expressed genes (DEGs) between five brain regions of AD cases and healthy controls. Subsequent analysis revealed pathways that were altered in each brain region, of which the GABAergic synapse pathway and the retrograde endocannabinoid signaling pathway were shared between all AD affected brain regions except the cerebellum, which is relatively less sensitive to the effects of AD. Furthermore, we obtained common robust DEGs between these two pathways and predicted three miRNAs as potential candidates targeting these genes; hsa-mir-17-5p, hsa-mir-106a-5p and hsa-mir-373-3p. Three transcription factors (TFs) were also identified as the potential upstream regulators of the robust DEGs; ELK-1, GATA1 and GATA2. Our results provide the foundation for further research investigating the role of these pathways in AD pathogenesis, and potential application of these miRNAs and TFs as therapeutic and diagnostic targets.

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Section: Discussionsupporting

confidence: 70%

Key Genes and Biochemical Networks in Various Brain Regions Affected in Alzheimer’s Disease

Abyadeh

Tofigh

Hosseinian

et al. 2022

Cells

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“…A recent autopsy study indicated that p-tau at threonine 217 (p-tau217) was the most important phosphorylation site in the differentiation between Alzheimer’s disease and control brain tissue ( Wesseling et al, 2020 ), and plasma p-tau217 has been considered a biomarker of AD ( Thijssen et al, 2021 ). Aβ and tau protein deposition can affect signal and substance transmission between neurons, leading to neuronal degeneration and death ( Bottero et al, 2021 ).…”

Section: Introductionmentioning

confidence: 99%

Epigenetics in Alzheimer’s Disease

Gao

Chen

Yang

et al. 2022

Front. Aging Neurosci.

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Alzheimer’s disease (AD) is a neurodegenerative disease with unknown pathogenesis and complex pathological manifestations. At present, a large number of studies on targeted drugs for the typical pathological phenomenon of AD (Aβ) have ended in failure. Although there are some drugs on the market that indirectly act on AD, their efficacy is very low and the side effects are substantial, so there is an urgent need to develop a new strategy for the treatment of AD. An increasing number of studies have confirmed epigenetic changes in AD. Although it is not clear whether these epigenetic changes are the cause or result of AD, they provide a new avenue of treatment for medical researchers worldwide. This article summarizes various epigenetic changes in AD, including DNA methylation, histone modification and miRNA, and concludes that epigenetics has great potential as a new target for the treatment of AD.

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“…Worldwide, nearly 50 million people are affected by AD and other dementias and this number is projected to continue to double every 20 years ( Grande et al, 2020 ). Despite this widespread prevalence, pathophysiology is still poorly understood ( Bottero et al, 2021 ) and neuronal destruction “cannot be prevented, slowed, or cured” ( Leandrou et al, 2020 , p.176).…”

Section: Introductionmentioning

confidence: 99%

Behavioral and Psychological Symptoms of Dementia as a Means of Communication: Considerations for Reducing Stigma and Promoting Person-Centered Care

Warren

2022

Front. Psychol.

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Dementia has rapidly become a major global health crisis. As the aging population continues to increase, the burden increases commensurately on both individual and societal levels. The behavioral and psychological symptoms of dementia (BPSD) are a prominent clinical feature of Alzheimer’s disease and related dementias (ADRD). BPSD represent a myriad of manifestations that can create significant challenges for persons living with dementia and their care providers. As such, BPSD can result in detriments to social interaction with others, resulting in harm to the psychosocial health of the person with dementia. While brain deterioration can contribute to BPSD as the disease progresses, it may be confounded by language and communication difficulties associated with ADRD. Indeed, when a person with dementia cannot effectively communicate their needs, including basic needs such as hunger or toileting, nor symptoms of pain or discomfort, it may manifest as BPSD. In this way, a person with dementia may be attempting to communicate with what little resources are available to them in the form of emotional expression. Failing to recognize unmet needs compromises care and can reduce quality of life. Moreover, failing to fulfill said needs can also deteriorate communication and social bonds with loved ones and caregivers. The aim of this review is to bring the differential of unmet needs to the forefront of BPSD interpretation for both formal and informal caregivers. The overarching goal is to provide evidence to reframe the approach with which caregivers view the manifestations of BPSD to ensure quality of care for persons with dementia. Understanding that BPSD may, in fact, be attempts to communicate unmet needs in persons with dementia may facilitate clinical care decisions, promote quality of life, reduce stigma, and foster positive communications.

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Key Disease Mechanisms Linked to Alzheimer’s Disease in the Entorhinal Cortex

Cited by 24 publications

References 133 publications

Key Genes and Biochemical Networks in Various Brain Regions Affected in Alzheimer’s Disease

Key Genes and Biochemical Networks in Various Brain Regions Affected in Alzheimer’s Disease

Epigenetics in Alzheimer’s Disease

Behavioral and Psychological Symptoms of Dementia as a Means of Communication: Considerations for Reducing Stigma and Promoting Person-Centered Care

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