Medicine and Health Sciences Commons^™

Efficient Production Of A Mature And Functional Gamma Secretase Protease, Imran Khan, Sudarsan Krishnaswamy, Miheer Sabale, David M. Groth, Linda Wijaya, Michael Morici, Imre Berger, Christiane Schaffitzel, Paul E. Fraser, Ralph N. Martins, Giuseppe Verdile

Research outputs 2014 to 2021

Baculoviral protein expression in insect cells has been previously used to generate large quantities of a protein of interest for subsequent use in biochemical and structural analyses. The MultiBac baculovirus protein expression system has enabled, the use of a single baculovirus to reconstitute a protein complex of interest, resulting in a larger protein yield. Using this system, we aimed to reconstruct the gamma (γ)-secretase complex, a multiprotein enzyme complex essential for the production of amyloid-β (Aβ) protein. A MultiBac vector containing all components of the γ-secretase complex was generated and expression was observed for all components. The complex was active …

Alterations In Serum Kynurenine Pathway Metabolites In Individuals With High Neocortical Amyloid-Β Load: A Pilot Study, Pratishtha Chatterjee, Kathryn Goozee, Chai K. Lim, Ian James, Kaikai Shen, Kelly R. Jacobs, Hamid R. Sohrabi, Tejal Shah, Prita R. Asih, Preeti Dave, Candice Manyan, Kevin Taddei, David B. Lovejoy, Roger Chung, Gilles J. Guillemin, Ralph N. Martins

Research outputs 2014 to 2021

The kynurenine pathway (KP) is dysregulated in neuroinflammatory diseases including Alzheimer's disease (AD), however has not been investigated in preclinical AD characterized by high neocortical amyloid-β load (NAL), prior to cognitive impairment. Serum KP metabolites were measured in the cognitively normal KARVIAH cohort. Participants, aged 65-90 y, were categorised into NAL+ (n = 35) and NAL- (n = 65) using a standard uptake value ratio cut-off = 1.35. Employing linear models adjusting for age and APOEϵ4, higher kynurenine and anthranilic acid (AA) in NAL+ versus NAL- participants were observed in females (kynurenine, p = 0.004; AA, p = 0.001) but …

White Matter Hyperintensities And The Mediating Role Of Cerebral Amyloid Angiopathy In Dominantly-Inherited Alzheimer’S Disease, Seonjoo Lee, Molly E. Zimmerman, Atul Narkhede, Sara E. Nasrabady, Giuseppe Tosto, Irene B. Meier, Tammie L.S. Benzinger, Daniel S. Marcus, Anne M. Fagan, Nick C. Fox, Nigel J. Cairns, David M. Holtzman, Virginia Buckles, Bernardino Ghetti, Eric Mcdade, Ralph Martins, Andrew J. Saykin, Colin L. Masters, John M. Ringman, Stefan Fӧrster, Peter R. Schofield, Reisa A. Sperling, Keith A. Johnson, Jasmeer P. Chhatwal, Stephen Salloway, Stephen Correia, Clifford R. Jack, Jr, Michael Weiner, Randall J. Bateman, John C. Morris, Richard Mayeux, Adam M. Brickman

Research outputs 2014 to 2021

Introduction: White matter hyperintensity (WMH) volume on MRI is increased among presymptomatic individuals with autosomal dominant mutations for Alzheimer’s disease (AD). One potential explanation is that WMH, conventionally considered a marker of cerebrovascular disease, are a reflection of cerebral amyloid angiopathy (CAA) and that increased WMH in this population is a manifestation of this vascular form of primary AD pathology. We examined whether the presence of cerebral microbleeds, a marker of CAA, mediates the relationship between WMH and estimated symptom onset in individuals with and without autosomal dominant mutations for AD.

Participants and methods: Participants (n = 175, …