Autoimmune Mechanisms of Interferon Hypersensitivity and Neurodegenerative Diseases: Down Syndrome.

Down syndrome (DS), also known as trisomy 21 (T21), is associated with interferon (IFN) hypersensitivity, as well as predilections for Alzheimer's dementia (AD) and various autoimmune diseases. IFN- and IFN- receptors are encoded on chromosome 21 (Ch21). It remains unclear how other Ch21 genes contribute to the neuropathological features of DS/T21.

The recombinant vaccinia virus gene product, B18R, neutralizes interferon alpha and alleviates histopathological complications in an HIV encephalitis mouse model.

Interferon-alpha (IFN-α) has been identified as a neurotoxin that plays a prominent role in human immunodeficiency virus (HIV)-associated neurocognitive disorders and HIV encephalitis (HIVE) pathology. IFN-α is associated with cognitive dysfunction in other inflammatory diseases where IFN-α is upregulated. Trials of monoclonal anti-IFN-α antibodies have been generally disappointing possibly due to high specificity to limited IFN-α subtypes and low affinity.