Microglial Networks inAlzheimer’s diseaseJohn Hardy j.hardy@ucl.ac.ukUCL Institute of Neurology UnitedKingdom
Risk Loci for Alzheimer’s Disease (~6000Samples: General Lessons hold true as Samplenumbers increase)BIN1, bridging integr...
Normal Functioning CR1 and TREM2Promote Neuroprotection by Microglia
Loss of Function of CR1 and TREM2Promotes Inflammation and NeurotoxicityTNFa, tumor necrosis factor alpha.
An introduction to the UK Brain ExpressionConsortium (UKBEC) data setFrontal cortex (n=83)Temporal cortex (n=72)Occipital ...
TREM2 is a “hub” gene within its module inmultiple brain regions including hippocampus(Forabosco et al. NBA June 2013)Hipp...
Microglial networks in alzheimer’s disease
Microglial networks in alzheimer’s disease
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Microglial networks in alzheimer’s disease

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Microglial networks in alzheimer’s disease

  1. 1. Microglial Networks inAlzheimer’s diseaseJohn Hardy j.hardy@ucl.ac.ukUCL Institute of Neurology UnitedKingdom
  2. 2. Risk Loci for Alzheimer’s Disease (~6000Samples: General Lessons hold true as Samplenumbers 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 ~4Cholesterol metabolism: coding andexpressionCLU OR ~1.4Cholesterol metabolism: complementcascade—not coding, not simpleexpressionPICALM OR ~1.4 Endosomal vesicle recycling? Not codingABCA7 OR ~1.3Cholesterol metabolism: not known butGly1527Ala is possibleCR1 OR ~1.4Complement cascade: verycomplicated—probably sequence andexpressionBIN1 OR ~1.2 Endosomal vesicle recycling? Not codingMS4AE OR ~1.2 Cell surface protein: not coding
  3. 3. Normal Functioning CR1 and TREM2Promote Neuroprotection by Microglia
  4. 4. Loss of Function of CR1 and TREM2Promotes Inflammation and NeurotoxicityTNFa, tumor necrosis factor alpha.
  5. 5. An introduction to the UK Brain ExpressionConsortium (UKBEC) data setFrontal 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-WIDEEXPRESSIONFrom EACH brainsample 10 brain regionsAffy HumanExon 1.0 STarraysCONTROLHUMANBRAINSN = 134ONLY samples coming from a single brain bank, MRC Sudden Death Brain Bank
  6. 6. TREM2 is a “hub” gene within its module inmultiple brain regions including hippocampus(Forabosco et al. NBA June 2013)Hippocampus

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