Scientific Focus
Alzheimer’s Disease as well as vascular cognitive impairment are major health problems on our society. In fact, up to 80% of all dementia cases present themselves in a co-morbid manner with both AD and vascular cognitive impairment present in the patient. Hence, we are conducting basic research on the coocurrence of the two diseases to investigate underlying mechanisms and potential biomarkers. The neurovascular unit consist of multiple different cells that work in close coordination to regulates blood flow and blood brain barrier integrity and is of particular interest to us, as it is a common target in both diseases. We use a variety of methods to investigate disease related mechanisms on the genetic, functional and molecular level.
Methods
in vivo 2-Photon imaging, acute brain slice imaging, confocal microscopy, scRNA sequencing, primary cell culture, immunohistochemistry, molecular biology, protein biochemistry.
Selected Publications
Microglia Phenotypes Converge in Aging and Neurodegenerative Disease. M. Candlish and JK Hefendehl. Frontiers in Neurology May 2021
Medin aggregation causes cerebrovascular dysfunction in aging wild-type mice. K. Degenhardt, J Wagner, A Skodras, M Candlish, AJ Koppelmann, K Wild, R Maxwell, C Rotermund, F von Zweydorf, CJ Gloeckner, HA Davies, J Madine, D Del Turco, R Feederle, T Lashley, TDeller, P Kahle, J K Hefendehl, M Jucker, and JJ Neher. PNAS Sep. 2020
Mapping synaptic glutamate transporter dysfunction in vivo to regions surrounding Aβ plaques by iGluSnFR Two- Photon imaging. JK. Hefendehl, J. LeDue, R. Ko, T. Murphy, B.A. MacVicar. Nature Comm Oct 2016
Comment on “ApoE-Directed Therapeutics Rapidly Clear b-Amyloid and Reverse Deficits in AD Mouse Models”. Veeraraghavalu K,* Zhang C,* Miller S,* Hefendehl JK,* Rajapaksha TW,* Ulrich J,* Jucker M, Holtzman DM, Tanzi RE , Vassar R, Sisodia SS. (shared first authorship). Science 2013 Jan 22 340, 924 (2013)
Long-term in vivo Imaging of β-Amyloid Plaque Appearance and Growth in a Mouse Model of Cerebral β-Amyloidosis. Hefendehl JK*, Wegenast-Braun BM*, Liebig C, Eicke D, Milford D, Calhoun ME, Eichner M, Jucker M.. J Neurosci. 2011 Jan 12;31(2):624-9.