Citations 3
Microglial translational profiling reveals a convergent APOE pathway from aging, amyloid, and tau
Kang, Silvia S. , Ebbert, Mark , Baker, Kelsey E., Cook, Casey , Wang, Xuewei , Sens, Jonathon , Kocher, Jeanne-Pierre, Petrucelli, Leonard , Fryer, John Denis , Ebbert, Mark T W , Sens, Jonathon P, Fryer, John D
Journal of Experimental Medicine | August 6, 2018 | Volume: 215 | Issue: 9 | Pages: 2235-2245
Alzheimer’s disease (AD) is an age-associated neurodegenerative disease characterized by amyloidosis, tauopathy, and activation of microglia, the brain resident innate immune cells. We show that a RiboTag translational profiling approach can bypass biases due to cellular enrichment/cell sorting. Using this approach in models of amyloidosis, tauopathy, and aging, we revealed a common set of alterations and identified a central APOE-driven network that converged on CCL3 and CCL4 across all conditions. Notably, aged females demonstrated a significant exacerbation of many of these shared transcripts in this APOE network, revealing a potential mechanism for increased AD susceptibility in females. This study has broad implications for microglial transcriptomic approaches and provides new insights into microglial pathways associated with different pathological aspects of aging and AD.
Behavioral and transcriptomic analysis of Trem2-null mice: not all knockout mice are created equal
Kang, Silvia S. , Kurti, Aishe, Baker, Kelsey E., Liu, Chia‐Chen , Ulrich, Jason D. , Bu, Guojun , Fryer, John Denis , Fryer, John D., Liu, Chia-Chen , Bu, Guojun , Colonna, Marco , Holtzman, David M.
Human Molecular Genetics | October 10, 2017 | Volume: 27 | Issue: 2 | Pages: 211-223
Loss of clusterin shifts amyloid deposition to the cerebrovasculature via disruption of perivascular drainage pathways
Wojtas, Aleksandra, Kang, Silvia S. , Olley, Benjamin M., Gatherer, Maureen, Shinohara, Mitsuru , Lozano, Patricia A., Liu, Chia‐Chen , Kurti, Aishe, Baker, Kelsey E., Yue, Mei, Petrucelli, Leonard , Bu, Guojun , Fryer, John Denis , Wojtas, Aleksandra M, Fryer, John D., Dickson, Dennis W. , Carare, Roxana Octavia , Liu, Chia-Chen , Bu, Guojun
Proceedings of the National Academy of Sciences | July 12, 2017 | Volume: 114 | Issue: 33 | Pages: No page available
Significance Deposition of amyloid-β (Aβ) peptide in the form of parenchymal plaques and Aβ accumulation in the walls of cerebral vessels as cerebral amyloid angiopathy (CAA) are pathological hallmarks of Alzheimer’s disease (AD). The clusterin ( CLU ) gene, which confers AD risk, is associated with amyloid deposition. Here we show that loss of CLU promotes cerebrovascular CAA, yet significantly reduces the amount of parenchymal plaques by altering perivascular drainage of Aβ in the APP/PS1 mouse model of AD. The absence of CLU in these mice is associated with a lower number of hemorrhages and a decrease in inflammation. These results suggest that CLU functions as a major Aβ chaperone to maintain Aβ solubility along interstitial fluid drainage pathways and prevent CAA formation.