Chronic HIV infection leads to an Alzheimer's disease like illness. Involvement of the kynurenine pathway

Abstract

HIV disease is complicated by the development of a subcortical dementing illness known as AIDS dementia complex (ADC). Highly active antiretroviral therapy (HAART) has effectively lengthened HIV infected patients' life expectancy; indeed some are approaching an age where the risk of Alzheimer's disease (AD) is starting to become significant. Furthermore, many such patients have hyperlipidemia, which increases the risk of AD. Consequently, it is hypothesized that HIV infected patients are at an increased risk of AD or an illness that is very much like it. While this is a subcortical dementia and as such is quite different from AD, there are similarities especially in regard to the important role of neuroinflammation. Activation of the tryptophan metabolism via the kynurenine pathway (KP) and more particularly production of one of its end-products, excitotoxin quinolinic acid (QUIN), may play a central role in the amplification of the inflammatory mechanisms, amyloid plaque formation and even increase the rate of viral infection of brain cells.