Amyloid beta accumulation in HIV-1-infected brain: The role of the blood brain barrier

Abstract

In recent years, we face an increase in the aging of the HIV-1-infected population, which is not only due to effective antiretroviral therapy but also to new infections among older people. Even with the use of the antiretroviral therapy, HIV-associated neurocognitive disorders represent an increasing problem as the HIV-1-infected population ages. Increased amyloid beta (Aβ) deposition is characteristic of HIV-1-infected brains, and it has been hypothesized that brain vascular dysfunction contributes to this phenomenon, with a critical role suggested for the blood-brain barrier in brain Aβ homeostasis. This review will describe the mechanisms by which the blood-brain barrier may contribute to brain Aβ accumulation, and our findings in the context of HIV-1 infection will be discussed.

Figure 1. Schematic diagram of HIV-1-induced Aβ accumulation in brain endothelial cells

HIV-1-induced Aβ accumulation in brain endothelial cells is lipid raft/caveolae-dependent, involving LRP1/RAGE and the Ras-MAPK pathway. These events can lead to brain amyloid deposition and associated neurocognitive disorders. Abbreviations: Cav-1, caveolin-1; LRP1, lipoprotein receptor related protein 1; RAGE, receptor for advanced glycation end products; MAPK, mitogen activated protein kinase; TJ, tight junction; HAND, HIV-associated neurocognitive disorders.