HIV Neuroinfection and Alzheimer’s Disease: Similarities and Potential Links?

Canet, Geoffrey; Dias, Chloé; Gabelle, Audrey; Simonin, Yannick; Gosselet, Fabien; Marchi, Nicola; Makinson, Alain; Tuaillon, Édouard; Perre, Philippe Van de; Givalois, Laurent; Salinas, Sara

doi:10.3389/fncel.2018.00307

Cited by 66 publications

(51 citation statements)

References 154 publications

(182 reference statements)

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“…More recently, insulin deficiency and insulin resistance have been associated with pathological abnormalities akin to Alzheimer's disease type neurodegeneration [41]. This is similar to the neurotoxic cytokine cascade reported for HAND and has led to the speculation that Alzheimer's disease is "type 3 diabetes" [42][43][44][45][46].…”

Section: Associated Comorbid Neurocognitive Changesmentioning

confidence: 80%

The Increase of HIV-1 Infection, Neurocognitive Impairment, and Type 2 Diabetes in The Rio Grande Valley

Garza

Rodrigo

Fernandez

et al. 2020

CHR

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: The Human Immunodeficiency Virus (HIV-1) infection remains a persistent predicament for the State of Texas, ranking seventh among the most documented HIV cases in the United States. In this regard, the Rio Grande Valley (RGV) in South Texas is considered as one of the least investigated areas of the state with respect to HIV infection and HIV associated comorbidities. Considering the 115% increase in average HIV incidence rates per 100,000 within the RGV from 2007-2015, it is worth characterizing this population with respect to their HIV-1 infection, HIV-1 Associated Neurocognitive Disorders (HAND), and the association of treatment with combined antiretroviral therapy (cART). Moreover, the increased rate of Type-2 Diabetes (T2D) in the RGV population is intertwined with that of HIV-1 infection facing challenges due to the lack of knowledge about prevention to inadequate access to healthcare. Hence, the role of T2D in the development of HAND among the people living with HIV (PLWH) in the RGV will be reviewed to establish a closer link between T2D and HAND in cART-treated patients of the RGV.

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Section: Associated Comorbid Neurocognitive Changesmentioning

confidence: 80%

The Increase of HIV-1 Infection, Neurocognitive Impairment, and Type 2 Diabetes in The Rio Grande Valley

Garza

Rodrigo

Fernandez

et al. 2020

CHR

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“…Analysis of the disease-gene associations showed the differentially regulated genes were also implicated in other ailments with impaired cognition (Table S4). Specifically, Alzheimer's disease and tauopathy were enriched in the disease ontology (Table S4), suggesting potential convergence of the two pathologies [41].…”

Section: Molecular Signature Of Mnd Involves Coordinated Biological Rmentioning

confidence: 99%

Transcriptomic analysis of brain tissues identifies a role for CCAAT enhancer binding protein β in HIV-associated neurocognitive disorder

Canchi

Swinton

Rissman

et al. 2020

J Neuroinflammation

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Background: HIV-associated neurocognitive disorders (HAND) persist in the era of combined antiretroviral therapy (ART) despite reductions in viral load (VL) and overall disease severity. The mechanisms underlying HAND in the ART era are not well understood but are likely multifactorial, involving alterations in common pathways such as inflammation, autophagy, neurogenesis, and mitochondrial function. Newly developed omics approaches hold potential to identify mechanisms driving neuropathogenesis of HIV in the ART era. Methods: In this study, using 33 postmortem frontal cortex (FC) tissues, neuropathological, molecular, and biochemical analyses were used to determine cellular localization and validate expression levels of the prolific transcription factor (TF), CCAAT enhancer binding protein (C/EBP) β, in brain tissues from HIV+ cognitively normal and HAND cases. RNA sequencing (seq) and transcriptomic analyses were performed on FC tissues including 24 specimens from wellcharacterized people with HIV that had undergone neurocognitive assessments. In vitro models for brain cells were used to investigate the role of C/EBPβ in mediating gene expression.Results: The most robust signal for TF dysregulation was observed in cases diagnosed with minor neurocognitive disorder (MND) compared to cognitive normal (CN) cases. Of particular interest, due to its role in inflammation, autophagy and neurogenesis, C/EBPβ was significantly upregulated in MND compared to CN brains. C/EBPβ was increased at the protein level in HAND brains. C/EBPβ levels were significantly reduced in neurons and increased in astroglia in HAND brains compared to CN. Transfection of human astroglial cells with a plasmid expressing C/ EBPβ induced expression of multiple targets identified in the transcriptomic analysis of HAND brains, including dynamin-1-like protein (DNM1L) and interleukin-1 receptor-associated kinase 1. Recombinant HIV-Tat reduced and increased C/EBPβ levels in neuronal and astroglial cells, respectively.(Continued on next page) Conclusions: These findings are the first to present RNAseq-based transcriptomic analyses of HIV+ brain tissues, providing further evidence of altered neuroinflammation, neurogenesis, mitochondrial function, and autophagy in HAND. Interestingly, these studies confirm a role for CEBPβ in regulating inflammation, metabolism, and autophagy in astroglia. Therapeutic strategies aimed at transcriptional regulation of astroglia or downstream pathways may provide relief to HIV+ patients at risk for HAND and other neurological disorders.

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Section: Molecular Signature Of Mnd Involves Coordinated Biological Rmentioning

confidence: 99%

Transcriptomic analysis of brain tissues identifies a role for CCAAT enhancer binding protein β in HIV-associated neurocognitive disorders

Canchi

Swinton

Rissman

et al. 2020

Preprint

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Background: HIV-associated neurocognitive disorders (HAND) persist in the era of combined antiretroviral therapy (ART) despite reductions in viral load (VL) and overall disease severity. The mechanisms underlying HAND in ART era are not well understood but are likely multifactorial, involving alterations in common pathways such as inflammation, autophagy, neurogenesis, and mitochondrial function. Newly developed omics approaches hold potential to identify mechanisms driving neuropathogenesis of HIV in the ART era. Methods: In this study, using 33 postmortem frontal cortex (FC) tissues, neuropathological, molecular, and biochemical analyses were used to determine cellular localization and validate expression levels of the prolific transcription factor (TF), CCAAT enhancer binding protein (C/EBP) ß, in brain tissues from HIV+ cognitively normal and HAND cases. RNA sequencing (seq) and transcriptomics analyses were performed on FC tissues including 24 specimens from well-characterized people with HIV that had undergone neurocognitive assessments. In vitro models for brain cells were used to investigate the role of C/EBPß in mediating gene expression. Results: The most robust signal for TF dysregulation was observed in cases diagnosed with Minor Neurocognitive Disorders (MND) compared to cognitive normal (CN) cases. Of particular interest, due to its role in inflammation, autophagy and neurogenesis, C/EBPß was significantly upregulated in MND compared to CN brains. C/EBPß was increased at the protein level in HAND brains. C/EBPß levels were significantly reduced in neurons and increased in astroglia in HAND brains compared to CN. Transfection of human astroglial cells with a plasmid expressing C/EBPß induced expression of multiple targets identified in the transcriptomic analysis of HAND brains, including dynamin-1-like protein (DNM1L) and interleukin-1 receptor-associated kinase 1. Recombinant HIV-Tat reduced and increased C/EBPß levels in neuronal and astroglial cells, respectively. Conclusions: These findings are the first to present RNAseq-based transcriptomic analyses of HIV+ brain tissues, providing further evidence of altered neuroinflammation, neurogenesis, mitochondrial function, and autophagy in HAND. Interestingly, these studies confirm a role for CEBPß in regulating inflammation, metabolism, and autophagy in astroglia. Therapeutic strategies aimed at transcriptional regulation of astroglia or downstream pathways may provide relief to HIV+ patients at risk for HAND and other neurological disorders.

show abstract

HIV Neuroinfection and Alzheimer’s Disease: Similarities and Potential Links?

Cited by 66 publications

References 154 publications

The Increase of HIV-1 Infection, Neurocognitive Impairment, and Type 2 Diabetes in The Rio Grande Valley

The Increase of HIV-1 Infection, Neurocognitive Impairment, and Type 2 Diabetes in The Rio Grande Valley

Transcriptomic analysis of brain tissues identifies a role for CCAAT enhancer binding protein β in HIV-associated neurocognitive disorder

Transcriptomic analysis of brain tissues identifies a role for CCAAT enhancer binding protein β in HIV-associated neurocognitive disorders

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