Laser-captured microglia in the Alzheimer’s and Parkinson’s brain reveal unique regional expression profiles and suggest a potential role for hepatitis B in Alzheimer’s brain

摘要

Expression array data from dozens of laboratories, including our own, show significant changes in expression of many genes in Alzheimer’s (AD) patients compared to normal controls (NC). These data typically rely on brain homogenates, and information about transcripts specific to microglia and other CNS cell types, which far outnumber microglia-specific transcripts, is lost. We therefore employed single cell laser capture methods to assess the full range of microglia-specific expression changes that occur in different brain regions (substantia nigra and hippocampus CA1), and disease states (AD, Parkinson’s disease (PD), and NC). Two novel pathways, neuronal repair and viral processing were identified. Based on KEGG analysis, one of the most significant viruses was hepatitis B virus (HBV) (FDR<.00000001). Immunohistochemistry with HBV core antibody in HBV-positive control, amnestic mild cognitive impairment, and AD cases, showed increased HBV immunoreactivity as disease pathology increases. These results are the first, to our knowledge, to show regional differences in human microglia. In addition, these data reveal new functions for microglia, and suggest a novel risk factor for AD.