title: PiB Fails to Map Amyloid Deposits in Cerebral Cortex of Aged Dogs with Canine Cognitive Dysfunction.
abstract: Dogs with Canine Cognitive Dysfunction (CCD) accumulate amyloid beta (Aβ) in the brain. As the cognitive decline and neuropathology of these old dogs share features with Alzheimer's disease (AD), the relation between Aβ and cognitive decline in animal models of cognitive decline is of interest to the understanding of AD. However, the sensitivity of the biomarker Pittsburgh Compound B (PiB) to the presence of Aβ in humans and in other mammalian species is in doubt. To test the sensitivity and assess the distribution of Aβ in dog brain, we mapped the brains of dogs with signs of CCD (n = 16) and a control group (n = 4) of healthy dogs with radioactively labeled PiB ([(11)C]PiB). Structural magnetic resonance imaging brain scans were obtained from each dog. Tracer washout analysis yielded parametric maps of PiB retention in brain. In the CCD group, dogs had significant retention of [(11)C]PiB in the cerebellum, compared to the cerebral cortex. Retention in the cerebellum is at variance with evidence from brains of humans with AD. To confirm the lack of sensitivity, we stained two dog brains with the immunohistochemical marker 6E10, which is sensitive to the presence of both Aβ and Aβ precursor protein (AβPP). The 6E10 stain revealed intracellular material positive for Aβ or AβPP, or both, in Purkinje cells. The brains of the two groups of dogs did not have significantly different patterns of [(11)C]PiB binding, suggesting that the material detected with 6E10 is AβPP rather than Aβ. As the comparison with the histological images revealed no correlation between the [(11)C]PiB and Aβ and AβPP deposits in post-mortem brain, the marked intracellular staining implies intracellular involvement of amyloid processing in the dog brain. We conclude that PET maps of [(11)C]PiB retention in brain of dogs with CCD fundamentally differ from the images obtained in most humans with AD.
authors.affiliation: Department of Clinical Veterinary and Animal Sciences, Faculty of Health and Medical Sciences, University of Copenhagen , Frederiksberg , Denmark.
authors.forename: Rikke
authors.initials: R
authors.lastname: Fast
authors.affiliation: Centre of Functionally Integrative Neuroscience (CFIN), Aarhus University , Aarhus , Denmark ; Department of Nuclear Medicine and PET Center, Aarhus University Hospital , Aarhus , Denmark.
authors.forename: Anders
authors.initials: A
authors.lastname: Rodell
authors.affiliation: Centre of Functionally Integrative Neuroscience (CFIN), Aarhus University , Aarhus , Denmark ; Department of Nuclear Medicine and PET Center, Aarhus University Hospital , Aarhus , Denmark ; Department of Neuroscience and Pharmacology, Faculty of Health and Medical Sciences, University of Copenhagen , Copenhagen , Denmark.
authors.forename: Albert
authors.initials: A
authors.lastname: Gjedde
authors.affiliation: Centre of Functionally Integrative Neuroscience (CFIN), Aarhus University , Aarhus , Denmark.
authors.forename: Kim
authors.initials: K
authors.lastname: Mouridsen
authors.affiliation: Department of Nuclear Medicine and PET Center, Aarhus University Hospital , Aarhus , Denmark.
authors.forename: Aage K
authors.initials: AK
authors.lastname: Alstrup
authors.affiliation: Department of Biomedicine, Faculty of Health, University of Aarhus , Aarhus , Denmark ; Department of Neurosurgery, Aarhus University Hospital , Aarhus , Denmark.
authors.forename: Carsten R
authors.initials: CR
authors.lastname: Bjarkam
authors.affiliation: Department of Biomedicine, Faculty of Health, University of Aarhus , Aarhus , Denmark.
authors.forename: Mark J
authors.initials: MJ
authors.lastname: West
authors.affiliation: Department of Clinical Veterinary and Animal Sciences, Faculty of Health and Medical Sciences, University of Copenhagen , Frederiksberg , Denmark.
authors.forename: Mette
authors.initials: M
authors.lastname: Berendt
authors.affiliation: Centre of Functionally Integrative Neuroscience (CFIN), Aarhus University , Aarhus , Denmark ; Department of Nuclear Medicine and PET Center, Aarhus University Hospital , Aarhus , Denmark.
authors.forename: Arne
authors.initials: A
authors.lastname: Møller
keywords: 6E10 immunohistochemistry; Alzheimer’s disease; Pittsburgh compound B; beta-amyloid; canine cognitive dysfunction; dog