Catherine Canon - Academia.edu (original) (raw)
Uploads
Papers by Catherine Canon
Nature Medicine, 2000
One hallmark of Alzheimer disease is the accumulation of amyloid β-peptide in the brain and its d... more One hallmark of Alzheimer disease is the accumulation of amyloid β-peptide in the brain and its deposition as plaques. Mice transgenic for an amyloid β precursor protein (APP) mini-gene driven by a platelet-derived (PD) growth factor promoter (PDAPP mice), which overexpress one of the disease-linked mutant forms of the human amyloid precursor protein, show many of the pathological features of Alzheimer disease, including extensive deposition of extracellular amyloid plaques, astrocytosis and neuritic dystrophy 1,2. Active immunization of PDAPP mice with human amyloid β-peptide reduces plaque burden and its associated pathologies 3. Several hypotheses have been proposed regarding the mechanism of this response 4,5. Here we report that peripheral administration of antibodies against amyloid β-peptide, was sufficient to reduce amyloid burden. Despite their relatively modest serum levels, the passively administered antibodies were able to enter the central nervous system, decorate plaques and induce clearance of preexisting amyloid. When examined in an ex vivo assay with sections of PDAPP or Alzheimer disease brain tissue, antibodies against amyloid β-peptide triggered microglial cells to clear plaques through Fc receptor-mediated phagocytosis and subsequent peptide degradation. These results indicate that antibodies can cross the blood-brain barrier to act directly in the central nervous system and should be considered as a therapeutic approach for the treatment of Alzheimer disease and other neurological disorders.
Proceedings of the National Academy of Sciences, 2003
Transgenic PDAPP mice, which express a disease-linked isoform of the human amyloid precursor prot... more Transgenic PDAPP mice, which express a disease-linked isoform of the human amyloid precursor protein, exhibit CNS pathology that is similar to Alzheimer's disease. In an age-dependent fashion, the mice develop plaques containing β-amyloid peptide (Aβ) and exhibit neuronal dystrophy and synaptic loss. It has been shown in previous studies that pathology can be prevented and even reversed by immunization of the mice with the Aβ peptide. Similar protection could be achieved by passive administration of some but not all monoclonal antibodies against Aβ. In the current studies we sought to define the optimal antibody response for reducing neuropathology. Immune sera with reactivity against different Aβ epitopes and monoclonal antibodies with different isotypes were examined for efficacy both ex vivo and in vivo . The studies showed that: ( i ) of the purified or elicited antibodies tested, only antibodies against the N-terminal regions of Aβ were able to invoke plaque clearance; ( ii...
Nature Medicine, 2000
One hallmark of Alzheimer disease is the accumulation of amyloid β-peptide in the brain and its d... more One hallmark of Alzheimer disease is the accumulation of amyloid β-peptide in the brain and its deposition as plaques. Mice transgenic for an amyloid β precursor protein (APP) mini-gene driven by a platelet-derived (PD) growth factor promoter (PDAPP mice), which overexpress one of the disease-linked mutant forms of the human amyloid precursor protein, show many of the pathological features of Alzheimer disease, including extensive deposition of extracellular amyloid plaques, astrocytosis and neuritic dystrophy 1,2. Active immunization of PDAPP mice with human amyloid β-peptide reduces plaque burden and its associated pathologies 3. Several hypotheses have been proposed regarding the mechanism of this response 4,5. Here we report that peripheral administration of antibodies against amyloid β-peptide, was sufficient to reduce amyloid burden. Despite their relatively modest serum levels, the passively administered antibodies were able to enter the central nervous system, decorate plaques and induce clearance of preexisting amyloid. When examined in an ex vivo assay with sections of PDAPP or Alzheimer disease brain tissue, antibodies against amyloid β-peptide triggered microglial cells to clear plaques through Fc receptor-mediated phagocytosis and subsequent peptide degradation. These results indicate that antibodies can cross the blood-brain barrier to act directly in the central nervous system and should be considered as a therapeutic approach for the treatment of Alzheimer disease and other neurological disorders.
Proceedings of the National Academy of Sciences, 2003
Transgenic PDAPP mice, which express a disease-linked isoform of the human amyloid precursor prot... more Transgenic PDAPP mice, which express a disease-linked isoform of the human amyloid precursor protein, exhibit CNS pathology that is similar to Alzheimer's disease. In an age-dependent fashion, the mice develop plaques containing β-amyloid peptide (Aβ) and exhibit neuronal dystrophy and synaptic loss. It has been shown in previous studies that pathology can be prevented and even reversed by immunization of the mice with the Aβ peptide. Similar protection could be achieved by passive administration of some but not all monoclonal antibodies against Aβ. In the current studies we sought to define the optimal antibody response for reducing neuropathology. Immune sera with reactivity against different Aβ epitopes and monoclonal antibodies with different isotypes were examined for efficacy both ex vivo and in vivo . The studies showed that: ( i ) of the purified or elicited antibodies tested, only antibodies against the N-terminal regions of Aβ were able to invoke plaque clearance; ( ii...