Browsing by Author "Petyuk, Vlad"

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    Neuropathological correlates and genetic architecture of microglial activation in elderly human brain
    (Springer Nature, 2019-01-24) Felsky, Daniel; Roostaei, Tina; Nho, Kwangsik; Risacher, Shannon L.; Bradshaw, Elizabeth M.; Petyuk, Vlad; Schneider, Julie A.; Saykin, Andrew; Bennett, David A.; De Jager, Philip L.; Radiology and Imaging Sciences, School of Medicine
    Microglia, the resident immune cells of the brain, have important roles in brain health. However, little is known about the regulation and consequences of microglial activation in the aging human brain. Here we report that the proportion of morphologically activated microglia (PAM) in postmortem cortical tissue is strongly associated with β-amyloid, tau-related neuropathology, and the rate of cognitive decline. Effect sizes for PAM measures are substantial, comparable to that of APOE ε4, the strongest genetic risk factor for Alzheimer's disease, and mediation models support an upstream role for microglial activation in Alzheimer's disease via accumulation of tau. Further, we identify a common variant (rs2997325) influencing PAM that also affects in vivo microglial activation measured by [11C]-PBR28 PET in an independent cohort. Thus, our analyses begin to uncover pathways regulating resident neuroinflammation and identify overlaps of PAM's genetic architecture with those of Alzheimer's disease and several other traits.
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    Parkinson's disease biomarkers: perspective from the NINDS Parkinson's Disease Biomarkers Program
    (Future Medicine, 2017-05) Gwinn, Katrina; David, Karen K.; Swanson-Fischer, Christine; Albin, Roger; St Hillaire-Clarke, Coryse; Sieber, Beth-Anne; Lungu, Codrin; Bowman, F. DuBois; Alcalay, Roy N.; Babcock, Debra; Dawson, Ted M.; Dewey, Richard B., Jr.; Foroud, Tatiana; German, Dwight; Huang, Xuemei; Petyuk, Vlad; Potashkin, Judith A.; Saunders-Pullman, Rachel; Sutherland, Margaret; Walt, David R.; West, Andrew B.; Zhang, Jing; Chen-Plotkin, Alice; Scherzer, Clemens R.; Vaillancourt, David E.; Rosenthal, Liana S.; Medical and Molecular Genetics, School of Medicine
    Biomarkers for Parkinson's disease (PD) diagnosis, prognostication and clinical trial cohort selection are an urgent need. While many promising markers have been discovered through the National Institute of Neurological Disorders and Stroke Parkinson's Disease Biomarker Program (PDBP) and other mechanisms, no single PD marker or set of markers are ready for clinical use. Here we discuss the current state of biomarker discovery for platforms relevant to PDBP. We discuss the role of the PDBP in PD biomarker identification and present guidelines to facilitate their development. These guidelines include: harmonizing procedures for biofluid acquisition and clinical assessments, replication of the most promising biomarkers, support and encouragement of publications that report negative findings, longitudinal follow-up of current cohorts including the PDBP, testing of wearable technologies to capture readouts between study visits and development of recently diagnosed (de novo) cohorts to foster identification of the earliest markers of disease onset.