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 the Alzheimer's brain

NEUROBIOLOGY OF AGING

卷:63

Article

Mastroeni, Diego^1,2  Nolz, Jennifer¹  Sekar, Shobana³  Delvaux, Elaine¹  Serrano, Geidy²  Cuyugan, Lori³  Liang, Winnie S.³  Beach, Thomas G.²  Rogers, Joseph⁴  Coleman, Paul D.^1,2 

[1] Arizona State Univ, Sch Life Sci, ASU Banner Biodesign Neurodegenerat Dis Res Ctr, Biodesign, 427 East Tyler Mall, Tempe, AZ 85287 USA

[2] Banner Sun Hlth Res Inst, Sun City, AZ USA

[3] Translat Genom Inst, Phoenix, AZ USA

[4] SRI Int, 333 Ravenswood Ave, Menlo Pk, CA 94025 USA

关键词: Microglia;    Alzheimer's disease;    Parkinson's disease;    Laser capture;    RNA sequencing;    Virus;    Synapse;   

DOI  :  10.1016/j.neurobiolaging.2017.10.019

来源: Elsevier

【 摘 要 】

Expression array data from dozens of laboratories, including our own, show significant changes in expression of many genes in Alzheimer's disease (AD) patients compared with normal controls. These data typically rely on brain homogenates, and information about transcripts specific to microglia and other central nervous system (CNS) cell types, which far outnumber microglia-specific transcripts, is lost. We therefore used 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, and normal controls). Two novel pathways, neuronal repair and viral processing were identified. Based on KEGG analysis (Kyoto Encyclopedia of Genes and Genomes, a collection of biological pathways), one of the most significant viruses was hepatitis B virus (HBV) (false discovery rate < 0.00000001). Immunohistochemical analysis using HBV-core antibody in HBV-positive control, amnestic mild cognitive impairment, and HBV-positive AD cases show 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. (C) 2017 Elsevier Inc. All rights reserved.

【 授权许可】

Free