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Targeting Amyloid Propagation in Alzheimer Disease: Structures, Immunology and Extracellular Vesicle Topology

Principal Investigator:
  • Neil Cashman, University of British Columbia
Team Members:
  • Cheryl Wellington, University of British Columbia
  • Ging-Yuek Hsiung, University of British Columbia
  • Weihong Song, University of British Columbia
  • Michael Smith Foundation for Health Research
  • Genome BC
  • Pacific Alzheimer Research Foundation

Project Overview

A treatment or prevention of Alzheimer’s disease is a top priority for medical science. Small aggregates of the protein amyloid-beta (A-beta), called oligomers, have been identified as being the primary cause of brain cell death in Alzheimer’s disease. However, there are many different subtypes of amyloid-beta oligomers and the specific one that causes disease is hotly debated by scientists. Neil Cashman and his team have identified an amyloid-beta oligomer-specific targeting site. The target is comprised of three amino acids in a distinct 3-dimensional arrangement. They have confirmed that immunological compounds (i.e. antibodies), which specifically recognize this amyloid-beta oligomer target site, exclusively detect amyloid-beta oligomers in the brains and spinal fluids of Alzheimer’s disease patients. Normal, healthy control patients, however, did not have this particular amyloid-beta oligomer targeting site in brain tissue or spinal fluids. Scientist know that all peoples, whether they have Alzheimer’s disease or not, have some amyloid-beta oligomers in their brains. Since amyloid-beta oligomers with our targeting site were only found in the brains of Alzheimer’s disease patients, it is possible that the team has defined a targeting site specific to the amyloid-beta oligomers that cause disease. They are exploiting this new knowledge to learn how toxic amyloid-beta oligomers spread from region-to-region in the brain causing disease. This knowledge is critical for the development of therapeutics to block the spread of neurodegeneration in the brain. In addition, they have found that some healthy people naturally develop immune responses against their amyloid-beta oligomer-specific target. Using samples from the Canadian Longitudinal Study of Aging, they will investigate the correlations between this response and onset of Alzheimer’s disease, perhaps producing a tool for early diagnosis of the disease.