Upload
alzheimer-research-forum
View
3.165
Download
0
Tags:
Embed Size (px)
Citation preview
Microglial Networks in Alzheimer’s disease
John Hardy [email protected]
UCL Institute of Neurology United Kingdom
Risk Loci for Alzheimer’s Disease (~6000
Samples: General Lessons hold true as Sample numbers increase)
BIN1, bridging integrator 1; OR, odds ratio.
Harold D, et al. Nat Genet. 2009;41:1088-1093; Hollingworth P, et al. Nat Genet. 2011;43:429-435; Lambert JC, et al. Nat Genet.
2009;41:1094-1099.
Apolipoprotein E4 OR ~4 Cholesterol metabolism: coding and expression
CLU OR ~1.4 Cholesterol metabolism: complement cascade—not coding, not simple expression
PICALM OR ~1.4 Endosomal vesicle recycling? Not coding
ABCA7 OR ~1.3 Cholesterol metabolism: not known but Gly1527Ala is possible
CR1 OR ~1.4 Complement cascade: very complicated—probably sequence and expression
BIN1 OR ~1.2 Endosomal vesicle recycling? Not coding
MS4AE OR ~1.2 Cell surface protein: not coding
Normal Functioning CR1 and TREM2 Promote Neuroprotection by Microglia
Loss of Function of CR1 and TREM2 Promotes Inflammation and Neurotoxicity
TNFa, tumor necrosis factor alpha.
An introduction to the UK Brain Expression Consortium (UKBEC) data set
Frontal cortex (n=83)
Temporal cortex (n=72)
Occipital cortex (n=77)
Hippocampus (n=86)
Intralobular white matter (n=83)
Cerebellar cortex (n=76)
Thalamus (n=81)
Putamen (n=77)
Substantia nigra (n=65)
Medulla (inf. olivary nuc, n=88)
GENOME-WIDE EXPRESSION
From EACH brain sample 10 brain regions
Affy Human Exon 1.0 ST
arrays
CONTROL HUMAN BRAINS N = 134
ONLY samples coming from a single brain bank, MRC Sudden Death Brain Bank
TREM2 is a “hub” gene within its module in multiple brain regions including hippocampus
(Forabosco et al. NBA June 2013)
Hippocampus