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SUMMARY:Broad complement inhibition in a mouse model of Alzheimer’s dise
 ase - Dr Elena M. Ribe\, Department of Psychiatry\, University of Oxford
DTSTART:20190220T160000Z
DTEND:20190220T170000Z
UID:TALK115816@talks.cam.ac.uk
CONTACT:Fiona Roby
DESCRIPTION:Alzheimer’s Disease (AD)\, the commonest form of dementia\, 
 is a neurodegenerative disorder characterized by the presence of extracell
 ular neuronal plaques\, intracellular neurofibrillary tangles\, neuroinfla
 mmation and neuronal cell loss. Although its aetiology remains largely unk
 nown\, recent genome-wide association studies (GWAS) have highlighted the 
 role of the immune system\, finding multiple immune related genes\, includ
 ing those encoding members of the complement cascades such as Complement R
 eceptor 1 (CR1)\, as susceptibility factors. Moreover\, complement compone
 nts have been found in association with plaques and tangles\, the histopat
 hological hallmarks of AD\, in postmortem AD brain. Thus\, a role for comp
 lement-mediated neuroinflammation in modulating disease progression has be
 en proposed and CR1 is a potential target for therapeutics development. In
  order to validate such an approach to disease modification\, we performed
  an in vivo study using two compounds targeting CR1 and thereby inhibiting
  complement at the level of the convertases C3/C5. Crry-Ig is a rodent fun
 ctional analogue of human CR1 that has been fused with the Fc portion of I
 gG (160 KDa) and Mirococept (APT070) is a 23KDa compound containing the 3 
 amino-terminal (Nt) repeats of human complement receptor 1 (CR1)\, current
 ly in phase 2a trials for kidney transplantation protection in man. Here w
 e show that the administration of these compounds to 14-15 month old Tg257
 6\, a mouse model of amyloidosis and neuroinflammation but not of tau path
 ology or neuronal cells loss\, resulted in substantial reduction in amyloi
 d pathology and microgliosis while the levels of GFAP reactive astrocytes 
 were not affected.\nTogether\, these findings suggest that complement inhi
 bition could be beneficial in slowing the progression of AD-related amyloi
 d pathology and in reducing neuroinflammation mediated by reactive microgl
 ia in the AD brain.\n
LOCATION:Lecture Theatre 2\, Department of Veterinary Medicine
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