Alzheimer's disease-like perturbations in HIV-mediated neuronal dysfunctions: understanding mechanisms and developing therapeutic strategies

Open Biol. 2020 Dec;10(12):200286. doi: 10.1098/rsob.200286. Epub 2020 Dec 23.


Excessive exposure to toxic substances or chemicals in the environment and various pathogens, including viruses and bacteria, is associated with the onset of numerous brain abnormalities. Among them, pathogens, specifically viruses, elicit persistent inflammation that plays a major role in Alzheimer's disease (AD) as well as dementia. AD is the most common brain disorder that affects thought, speech, memory and ability to execute daily routines. It is also manifested by progressive synaptic impairment and neurodegeneration, which eventually leads to dementia following the accumulation of Aβ and hyperphosphorylated Tau. Numerous factors contribute to the pathogenesis of AD, including neuroinflammation associated with pathogens, and specifically viruses. The human immunodeficiency virus (HIV) is often linked with HIV-associated neurocognitive disorders (HAND) following permeation through the blood-brain barrier (BBB) and induction of persistent neuroinflammation. Further, HIV infections also exhibited the ability to modulate numerous AD-associated factors such as BBB regulators, members of stress-related pathways as well as the amyloid and Tau pathways that lead to the formation of amyloid plaques or neurofibrillary tangles accumulation. Studies regarding the role of HIV in HAND and AD are still in infancy, and potential link or mechanism between both is not yet established. Thus, in the present article, we attempt to discuss various molecular mechanisms that contribute to the basic understanding of the role of HIV-associated neuroinflammation in AD and HAND. Further, using numerous growth factors and drugs, we also present possible therapeutic strategies to curb the neuroinflammatory changes and its associated sequels.

Keywords: Alzheimer's disease; HAND; HIV; microglia; neuroinflammation; neurotherapeutics.

Publication types

  • Review

MeSH terms

  • Alzheimer Disease / diagnosis
  • Alzheimer Disease / etiology
  • Amyloidogenic Proteins / metabolism
  • Animals
  • Astrocytes / metabolism
  • Biomarkers
  • Blood-Brain Barrier
  • Brain / metabolism
  • Brain / pathology
  • Brain / physiopathology
  • Brain / virology
  • Diagnosis, Differential
  • Disease Management
  • Disease Susceptibility*
  • HIV
  • HIV Infections / complications*
  • HIV Infections / virology
  • Humans
  • Microglia / metabolism
  • Neurodegenerative Diseases / diagnosis*
  • Neurodegenerative Diseases / etiology*
  • Neurodegenerative Diseases / therapy
  • Neurons / metabolism*
  • Neurons / virology
  • Risk Factors
  • Symptom Assessment


  • Amyloidogenic Proteins
  • Biomarkers