Divergent brain gene expression patterns associate with distinct cell-specific tau neuropathology traits in progressive supranuclear palsy

• DOI: 10.1007/s00401-018-1900-5
• Publication Date: 2018-08-22T15:15:18Z
• Authors: Mariet Allen; Xue Wang; Daniel J. Serie; Samantha L. Stric...; Jeremy D. Burgess; Shunsuke Koga; Curtis S. Younkin; Thuy T. Nguyen; Kimberly G. Malphrus; Sarah J. Lincoln; Melissa Alamprese; Kuixi Zhu; Rui Chang; Minerva M. Carras...; Naomi Kouri; Melissa E. Murray; Joseph S. Reddy; Cory Funk; Nathan D. Price; Todd E. Golde; Steven G. Younkin; Yan W. Asmann; Julia E. Crook; Dennis W. Dickson; Nilüfer Ertekin-T...
• Keywords: Neuropathology; Tauopathy

Progressive supranuclear palsy (PSP) is a neurodegenerative parkinsonian disorder characterized by tau pathology in neurons and glial cells. Transcriptional regulation has been implicated as potential mechanism conferring disease risk neuropathology for some PSP genetic variants. However, the role of transcriptional changes drivers distinct cell-specific lesions not explored. In this study, we integrated brain gene expression measurements, quantitative traits genome-wide genotypes from 268 autopsy-confirmed patients to identify associations with unique pathologies. We provide individual transcript network oligodendroglial (coiled bodies = CB), neuronal (neurofibrillary tangles NFT), astrocytic (tufted astrocytes TA) pathology, threads genomic annotations these findings. identified divergent patterns lesions, neuropathologies being most different. determined that NFT are positively associated co-expression enriched synaptic candidate genes, whereas TA microglial gene-enriched immune network. contrast, negatively system transcripts. Our findings have implications diverse molecular mechanisms underlie vulnerability PSP.