1. Microglial Networks in
Alzheimer’s disease
John Hardy j.hardy@ucl.ac.uk
UCL Institute of Neurology United
Kingdom

2. 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

5. Normal Functioning CR1 and TREM2
Promote Neuroprotection by Microglia

6. Loss of Function of CR1 and TREM2
Promotes Inflammation and Neurotoxicity
TNFa, tumor necrosis factor alpha.

7. 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

8. TREM2 is a “hub” gene within its module in
multiple brain regions including hippocampus
(Forabosco et al. NBA June 2013)
Hippocampus