Neurobiochemical Cross-talk Between COVID-19 and Alzheimer’s Disease

Rahman, Mohammad Azizur; Islam, Kamrul; Rahman, Saidur; Al-Amin, Al-Amin

doi:10.1007/s12035-020-02177-w

Cited by 98 publications

(108 citation statements)

References 80 publications

(113 reference statements)

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“…Angiotensin converting enzyme 2 (ACE2) is required for SARS-CoV-2 infection. Recently, it was reported that Ace2 gene and protein expression is elevated in AD patients compared to that in normal elderly individuals [11][12][13]. Consistent with these results, an increase in ACE2 expression results in an increased susceptibility to SARS-CoV-2 infection in elderly patients with AD.…”

Section: Introductionsupporting

confidence: 59%

Identifying new COVID-19 receptor Neuropilin-1 in severe Alzheimer’s diseases patients group brain using genome-wide association study approach

Lim

Yang

Kim

et al. 2021

Preprint

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Background Numerous studies have been conducted on different aspects of the COVID-19 (coronavirus disease 2019) pandemic, which is caused by SARS-CoV-2, since its emergence in late 2019. Mutual relations among SARS-CoV-2 and neuro-pathophysiological phenomena are continuously being demonstrated, and several underlying diseases, such as those in the elderly, are positively correlated with susceptibility to SARS-CoV-2 infection. The expression of angiotensin converting enzyme 2 (ACE2), which is required for SARS-CoV-2 infection, was recently demonstrated to be increased in Alzheimer’s disease (AD) patients. Methods Recent preclinical studies have shown that Neuropilin-1 (NRP1), which is a transmembrane protein with roles in neuronal development, axonal outgrowth, and angiogenesis, also plays a role in the infectivity of SARS-CoV-2. Thus, we hypothesized that NRP1 may be upregulated in AD patients and that a correlation between AD and SARS-CoV-2 NRP1-mediated infectivity may exist. We used an AD mouse model that mimics AD and performed high throughput total RNA-seq with brain tissue and whole blood. For quantification of NPR1 in AD, brain tissues and blood were subjected to western blotting and RT-qPCR analysis. In silico analysis for NRP1 expression in AD patients has been performed on the human hippocampus data sets (GSE4226, GSE1297). Results Many cases of severe symptom of COVID-19 are concentrated in elderly group who have complications such as diabetes, degenerative disease, and brain disorders. Total RNA-seq analysis showed that Nrp1 gene was commonly overexpressed in AD model. Similar to ACE2, NRP1 protein also strongly expressed in the AD brain tissues. Interestingly, in silico analysis revealed that the level of expression for NRP1 was distinct at age and AD progression. Conclusions Given that the NRP1 is highly expressed in AD, it will be important to understand and predict that NRP1 may a risk factor for SARS-CoV-2 infection in AD patients. This will support to development of potential therapeutic drug to reduce SARS-CoV-2 transmission.

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Section: Introductionsupporting

confidence: 59%

Identifying new COVID-19 receptor Neuropilin-1 in severe Alzheimer’s diseases patients group brain using genome-wide association study approach

Lim

Yang

Kim

et al. 2021

Preprint

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“…The dramatically elevated cytokine levels in patient serum have been closely correlated with COVID-19 fatality [97]. Plasma proteomics profiling has also identified cytokines/chemokines to be most perturbed in COVID-19 patients and implicated them as early biomarkers to monitor disease severity [72]. Based on this observation, AD and COVID-19 have similar inflammatory signaling.…”

Section: Direct Pathologic Changes Of Admentioning

confidence: 97%

“…Similarly, the case fatality ratio (CFR) of COVID-19 in the 80s and above is about 2-fold higher than the overall CFR in Italy, the first country affected by the pandemic after China [70]. Aging may induce production of reactive oxygen species, modification of epigenetics, and alterations of gene expression or non-coding RNA expression levels, which contribute to the pathogenesis of both AD and COVID-19 [71,72].…”

Section: The Potential Contributing Factors To the Ad-mediated Elevation Of Covid-19 Morbidity And Mortality Agingmentioning

confidence: 99%

COVID-19 and Alzheimer’s disease: how one crisis worsens the other

Xia

Wang

Zheng

2021

Transl Neurodegener

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Alzheimer’s disease (AD) has emerged as a key comorbidity of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). The morbidity and mortality of COVID-19 are elevated in AD due to multiple pathological changes in AD patients such as the excessive expression of viral receptor angiotensin converting enzyme 2 and pro-inflammatory molecules, various AD complications including diabetes, lifestyle alterations in AD, and drug-drug interactions. Meanwhile, COVID-19 has also been reported to cause various neurologic symptoms including cognitive impairment that may ultimately result in AD, probably through the invasion of SARS-CoV-2 into the central nervous system, COVID-19-induced inflammation, long-term hospitalization and delirium, and post-COVID-19 syndrome. In addition, the COVID-19 crisis also worsens behavioral symptoms in uninfected AD patients and poses new challenges for AD prevention. In this review, we first introduce the symptoms and pathogenesis of COVID-19 and AD. Next, we provide a comprehensive discussion on the aggravating effects of AD on COVID-19 and the underlying mechanisms from molecular to social levels. We also highlight the influence of COVID-19 on cognitive function, and propose possible routes of viral invasion into the brain and potential mechanisms underlying the COVID-19-induced cognitive impairment. Last, we summarize the negative impacts of COVID-19 pandemic on uninfected AD patients and dementia prevention.

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“…Athough IFTM3 is known to intercept and shuttle viral particles to the lysosomes 1 , Hur et al 2 uncovered a novel role for IFITM3 as a γ-secretase modulator that promotes Αβ production 2 , (i.e as a direct consequence of an innate immune response). Considering the accumulating evidence on common pathways between COVID-19 and Alzheimer's disease (AD) 3 , we aimed to examine their currently unexplored converge on IFITM3. Bulk and single cell RNA expression studies of AD patients, as well as COVID-19 infectomics converge on IFITM3 and FYN, its regulating kinase, as differentially expressed genes common between AD and COVID-19.…”

Section: Matters Arising Introductionmentioning

confidence: 99%

FYN, SARS-CoV-2, and IFITM3 in the Neurobiology of Alzheimer’s Disease: A Regulatory Feedback Loop Governing Tau and Aβ Pathology

Vavougios¹,

Breza²,

Nikou³

et al. 2020

Preprint

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Introduction IFITM3, an innate immune protein linked to COVID-19 severity, has recently been identified as a novel γ-secretase modulator. Independent research has shown that IFITM3 may facilitate SARS-CoV-2 neurotropism in an ACE2-independent manner. In a previous study, we had detected perturbations in IFITM3 networks in both the CNS and peripheral immune cells donated by AD patients.The purpose of this study is to explore the transcriptomic evidence of the SARS-CoV-2 / IFITM3 / AD interplay, validating previous findings from our group. Methods Exploratory analyses involved meta-analysis of bulk and single cell RNA data for IFITM3 and FYN differential expression. For confirmatory analyses, we performed gene set enrichment analysis (GSEA) on an AD gene signature from AD Consensus transcriptomics; using the Enrichr platform, we scrutinized COVID-19 datasets for significant, overlapping enriched biological networks. Results Bulk RNA data analysis revealed that IFITM3 and FYN were differentially expressed in two CNS regions in AD: the temporal cortex (AD vs. Controls, adj.p-value=1.3e-6) and the parahippocampal cortex (AD vs. controls, adj.p-value=0.012). Correspondingly, single cell RNA analysis of IFITM3 and FYN revealed that it was differentially expressed in neuronal cells donated from AD patients (astrocytes, microglia and oligodendrocyte precursor cells), when compared to controls. Discussion IFITM3 and by extent FYN were found as interactors within biological networks overlapping between AD and SARS-CoV-2 infection. SARS-CoV-2 SARS-CoV-2-mediated IFITM3 induction would mechanistically result in increased Aβ production. FYN recruitment by viral processes results in abrogation of both fusion of IFITM3 vesicles with lysosomes; immunoevasion, by FYN-mediated impairment of autophagy would then serve to promote impaired detoxification from Aβ, while propagating Tau pathology in an IFITM3-independent manner.

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Neurobiochemical Cross-talk Between COVID-19 and Alzheimer’s Disease

Cited by 98 publications

References 80 publications

Identifying new COVID-19 receptor Neuropilin-1 in severe Alzheimer’s diseases patients group brain using genome-wide association study approach

Identifying new COVID-19 receptor Neuropilin-1 in severe Alzheimer’s diseases patients group brain using genome-wide association study approach

COVID-19 and Alzheimer’s disease: how one crisis worsens the other

FYN, SARS-CoV-2, and IFITM3 in the Neurobiology of Alzheimer’s Disease: A Regulatory Feedback Loop Governing Tau and Aβ Pathology

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