Evaluating 2B3, a novel immunotherapy in PDAPP model of amyloid pathology

• Main Author: Evans, Charles
• Published: Cardiff University 2016
• Subjects: 616.8; BF Psychology
• Online Access: http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.699359

There are currently no disease-modifying therapies to halt or prevent the onset of Alzheimer’s disease (AD). Immunotherapy and antibodies targeting the neurotoxic amyloid-β (Aβ) peptide for its removal from the brain have provided a promising opportunity to provide disease-modifying therapies. However, despite promising pre-clinical data, any benefits have failed to translate to the clinic. This thesis evaluated an antibody approach that, rather than targeting amyloid per se, binds to the amyloid precursor protein (APP) at the β-secretase cleavage site to reduce amyloid production by steric hindrance (Thomas et al. 2011, 2013). The main hypothesis of this thesis was that 2B3 administration to aged PDAPP mice (Games et al. 1995), which overexpress a mutated form of APP (Indiana mutation; V717F), would (1) reduce APP metabolism and (2) Aβ production and (3) alleviate age-associated cognitive deficits in PDAPP mice.