Common transcriptional signatures in brain tissue from patients with HIV-associated neurocognitive disorders, Alzheimer's disease, and Multiple Sclerosis.
HIV-Associated Neurocognitive Disorders (HAND) is a common manifestation of HIV infection that afflicts about 50 % of HIV-positive individuals. As people with access to antiretroviral treatments live longer, HAND can be found in increasing segments of populations at risk for other chronic, neurodegenerative conditions such as Alzheimer's disease (AD) and Multiple Sclerosis (MS). If brain diseases of diverse etiologies utilize similar biological pathways in the brain, they may coexist in a patient and possibly exacerbate neuropathogenesis and morbidity. To test this proposition, we conducted comparative meta-analysis of selected publicly available microarray datasets from brain tissues of patients with HAND, AD, and MS. In pair-wise and three-way analyses, we found a large number of dysregulated genes and biological processes common to either HAND and AD or HAND and MS, or to all three diseases. The common characteristic of all three diseases was up-regulation of broadly ranging immune responses in the brain. In addition, HAND and AD share down-modulation of processes involved, among others, in synaptic transmission and cell-cell signaling while HAND and MS share defective processes of neurogenesis and calcium/calmodulin-dependent protein kinase activity. Our approach could provide insight into the identification of common disease mechanisms and better intervention strategies for complex neurocognitive disorders.
Molecular Virology Division, St. Luke's-Roosevelt Hospital Center, Columbia University, New York, NY 10019, USA. ab2612@columbia.edu
Alejandra
A
Borjabad
David J
DJ
Volsky
D015526:AIDS Dementia Complex / Q000235:genetics* / Q000276:immunology; D000544:Alzheimer Disease / Q000235:genetics* / Q000276:immunology; D017951:Antigen Presentation / Q000235:genetics; D001923:Brain Chemistry / Q000235:genetics*; D005625:Frontal Lobe / Q000737:chemistry / Q000378:metabolism; D020869:Gene Expression Profiling; D005819:Genetic Markers / Q000235:genetics*; D006801:Humans; D046228:Microarray Analysis; D009103:Multiple Sclerosis / Q000235:genetics* / Q000276:immunology; D014158:Transcription, Genetic / Q000235:genetics*; D059467:Transcriptome / Q000235:genetics
D005819:Genetic Markers