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

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

doi:10.3389/fncel.2018.00307

Abstract

Environmental factors such as chemicals, stress and pathogens are now widely believed to play important roles in the onset of some brain diseases, as they are associated with neuronal impairment and acute or chronic inflammation. Alzheimer’s disease (AD) is characterized by progressive synaptic dysfunction and neurodegeneration that ultimately lead to dementia. Neuroinflammation also plays a prominent role in AD and possible links to viruses have been proposed. In particular, the human immunodeficiency virus (HIV) can pass the blood-brain barrier and cause neuronal dysfunction leading to cognitive dysfunctions called HIV-associated neurocognitive disorders (HAND). Similarities between HAND and HIV exist as numerous factors involved in AD such as members of the amyloid and Tau pathways, as well as stress-related pathways or blood brain barrier (BBB) regulators, seem to be modulated by HIV brain infection, leading to the accumulation of amyloid plaques or neurofibrillary tangles (NFT) in some patients. Here, we summarize findings regarding how HIV and some of its proteins such as Tat and gp120 modulate signaling and cellular pathways also impaired in AD, suggesting similarities and convergences of these two pathologies.

Highlights

Neurodegenerative disorders, whether they are sporadic, genetic or due to pathogens, are caused by the specific impairment of different neural cell types and represent a major health issue in developed and developing countries
A concept that is clearly emerging though is that acute and chronic inflammation may pave the way to such disorders and neurotropic pathogens may represent likely candidates among environmental factors promoting this inflammatory/causative state
Large epidemiological studies are still needed to definitively conclude that aging human immunodeficiency virus (HIV)+ patients are more at risk of developing Alzheimer’s disease (AD), there are key physiological findings that suggest that this could be the case, though debate between neurologists exists (Ortega and Ances, 2014; Chakradhar, 2018)

Summary

Introduction

Neurodegenerative disorders, whether they are sporadic, genetic or due to pathogens, are caused by the specific impairment (cell death or cell dysfunction) of different neural cell types and represent a major health issue in developed and developing countries. Direct and indirect effects of HIV infection will lead to neuronal dysfunction (Figure 1): infected astrocytes and microglia release factors inducing neurotoxicity such as cytokines, chemokine and reactive oxygen species (ROS) (González-Scarano and Martín-García, 2005).

Results

Conclusion