Ludwig-Maximilians-Universität München & DZNE
Metabolic Biochemistry
Christian Haass holds the chair of Biochemistry at the Medical Faculty of the Ludwig-Maximilians-University in Munich, Germany. In addition, he is the speaker of the German Center for Neurodegenerative Diseases (DZNE-Munich) and the Munich Cluster for Systems Neurology (SyNergy). He completed his undergraduate work at the University of Heidelberg and graduated at the Center for Molecular Biology (ZMBH) with highest honors. He trained with a postdoctoral fellowship of the DFG (German Research Foundation) at the Center for Neurologic Diseases in the Selkoe laboratory at the Harvard Medical School. Within two years he was appointed to Assistant Professor of Neurology at Harvard. In 1999 he returned to Germany, where he first was appointed as a Professor of Molecular Biology at the Central Institute of Mental Health, Mannheim and four years later as the chairman of the Department of Metabolic Biochemistry of the Ludwigs-Maximilians-University Munich. Dr. Haass’ research focuses on the cellular and molecular mechanisms of Alzheimer’s disease and related disorders. He discovered the molecular mechanisms allowing physiological production of Amyloid -peptide and identified biological and pathological functions of secretases. His laboratory was also the first to reconstitute the gamma-secretase complex. More recently, Haass focusses on protective functions of microglia, which he attempts to therapeutically modify with selective antibodies. Haass received many prestigious awards, among them the Potemkin Award of the American Academy of Neurology, the MetLife Award, the Brain Prize, and the Gottfried Wilhelm Leibniz-Award of the DFG. He is a member of the European Molecular Biology Organization (EMBO), the Leopoldina (German Academy of Sciences) and the Bavarian Academy of Sciences.

Moderator of 2 Sessions

Session Type
SYMPOSIUM
Date
Wed, 16.03.2022
Session Time
04:15 PM - 06:00 PM
Room
ONSITE: 113
PLENARY LECTURE
Session Type
PLENARY LECTURE
Date
Sat, 19.03.2022
Session Time
08:30 AM - 09:00 AM
Room
ONSITE PLENARY: 115-117

Presenter of 2 Presentations

Discussants

Session Type
FORUM
Date
Fri, 18.03.2022
Session Time
03:50 PM - 04:50 PM
Room
ONSITE PLENARY: 115-117
Lecture Time
03:50 PM - 04:50 PM

THERAPEUTIC TARGETING OF MICROGLIAL FUNCTIONS

Session Type
SYMPOSIUM
Date
Wed, 16.03.2022
Session Time
04:15 PM - 06:00 PM
Room
ONSITE: 113
Lecture Time
04:15 PM - 04:30 PM

Abstract

Abstract Body

Triggering receptor expressed on myeloid cells 2 (TREM2) is essential for the transition of homeostatic microglia to a disease-associated microglial state. To enhance TREM2 activity, we sought to selectively increase the full-length protein on the cell surface via reducing its proteolytic shedding by A Disintegrin And Metalloproteinase (i.e., a-secretase) 10/17. We screened a panel of monoclonal antibodies against TREM2, with the aim to selectively compete for α-secretase-mediated shedding. Monoclonal antibody 4D9, which has a stalk region epitope close to the cleavage site, demonstrated dual mechanisms of action by stabilizing TREM2 on the cell surface and reducing its shedding, and concomitantly activating phospho-SYK signaling. 4D9 stimulated survival of macrophages and increased microglial uptake of myelin debris and amyloid β-peptide in vitro. In vivo target engagement was demonstrated in cerebrospinal fluid, where nearly all soluble TREM2 was 4D9-bound. Moreover, in a mouse model for Alzheimer’s disease related pathology, 4D9 reduced amyloidogenesis, enhanced microglial TREM2 expression, and reduced a homeostatic marker, suggesting a protective function by driving microglia toward a disease-associated state.

Hide