PiB Fails to Map Amyloid Deposits in Cerebral Cortex of Aged Dogs with Canine Cognitive Dysfunction.
Front Aging Neurosci
; 5: 99, 2013.
Article
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| MEDLINE
| ID: mdl-24416017
ABSTRACT
Dogs with Canine Cognitive Dysfunction (CCD) accumulate amyloid beta (Aß) in the brain. As the cognitive decline and neuropathology of these old dogs share features with Alzheimer's disease (AD), the relation between Aß 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 Aß in humans and in other mammalian species is in doubt. To test the sensitivity and assess the distribution of Aß 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 Aß and Aß precursor protein (AßPP). The 6E10 stain revealed intracellular material positive for Aß or AßPP, 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 AßPP rather than Aß. As the comparison with the histological images revealed no correlation between the [(11)C]PiB and Aß and AßPP 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.
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Colección:
01-internacional
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MEDLINE
Idioma:
En
Revista:
Front Aging Neurosci
Año:
2013
Tipo del documento:
Article
País de afiliación:
Dinamarca