QBI Neuroscience Seminar: 'Distinct microglial phenotypes in Alzheimer’s disease are controlled by amyloid plaque phagocytosis'

Event Details

Date:

Wednesday, 06 February 2019 - Wednesday, 06 February 2019

Time:

11:00 am - 12:00 pm

Room:

QBI Level 7 Auditorium

UQ Location:

Queensland Brain Institute (St Lucia)

URL:

http://www.qbi.uq.edu.au/neuroscience-seminars

Event category(s):

Full Description:: Dr Alexandra Grubman
Monash University, Clayton, VIC 3800

Title: Distinct microglial phenotypes in Alzheimer’s disease are controlled by amyloid plaque phagocytosis

Abstract: Microglia are brain immune cells that remove cellular and extracellular debris and regulate synaptic plasticity, maturation and removal. Recently altered microglial genomics, epigenomics and functions emerged as key contributors to Alzheimer’s disease (AD). Nonetheless, whether toxic microglial inflammatory cytokine secretion and aberrant synapse overpruning outweigh the beneficial amyloid clearance functions of microglia in AD remains highly controversial. To address these questions, we explored whether functional differences in amyloid plaque phagocytosis in a plaque-depositing AD mouse result from or contribute to the underlying molecular and functional diversity of microglia in AD.

Using a combination of bulk and single cell RNA-seq, and proteomics approaches, we showed that the amyloid plaque phagocytic subset of microglia are molecularly distinct from physiological microglia and from non-plaque containing microglia in AD brains. For instance, several later onset AD risk factors and their direct interacting partners are differentially expressed in plaque-containing microglia. We are now using stem cell derived microglia like cells to manipulate the signaling pathways involved in generating the plaque-associated microglial signature.