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Laura Emptage, Bill Milgram, Howard Dobson, Zoya Leonenko, Melanie Campbell; The Retina of the Cognitively Impaired Beagle Dog in Alzheimer’s Disease. Invest. Ophthalmol. Vis. Sci. 2013;54(15):6327.
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© ARVO (1962-2015); The Authors (2016-present)
Beagle dogs develop a form of Alzheimer’s disease (AD), Cognitive Dysfunction Syndrome, with symptoms similar to the disease in humans. We wished to determine the differences in expression of amyloid β between the retinas of cognitively impaired dogs and cognitively normal dogs; to characterize deposits and to compare the results to data previously obtained from retinas of humans with AD. Amyloid β is known to over express within the cerebrum of patients and dogs with AD, but the sensitivity of amyloid β deposits to fluorescent dyes is reported to differ in dog and human brains. Retinal amyloid β deposits would potentially allow objective, longitudinal tracking of AD in this species.
Cognitive testing on these dogs included a battery of non verbal cognitive function tests. Eyes were enucleated from two cognitively impaired and two normal dogs, euthanized for medical reasons unrelated to this study, then fixed in formalin. Post dissection, pieces of the retinas were flat mounted and stained with Thioflavin-S or Cucurmin and then studied using combined fluorescence and atomic force microscopy (AFM). Amyloid β deposits were expected close to the anterior surface of the flat mounted retinas of those with AD as found by our group previously in retinas from humans with AD. Areas of interest located by fluorescence were imaged with AFM at the nanoscale to characterize the amyloid β deposits.
Retinas of the cognitively impaired dogs had deposits stained with both Curcumin and Thioflavin-S (on separate pieces of retina). Amyloid β within the dog retina showed similar conformations to those in retinas from humans with AD, being either amorphous, “donut” like, or fibular. Amyloid β deposits were more numerous and larger in size within the retina of the more cognitively impaired dog. All retinas from control eyes were negative for fluorescent markers in both Thioflavin-S and Curcumin, and showed AFM images morphologically similar to human age matched control retinas.
Amyloid β deposits in retinas of cognitively impaired dogs have striking similarities in size, shape and location to amyloid β deposits in the retinas of humans with AD. Staining with Thioflavin-S was consistent, unlike reported inconsistent staining within the dog cerebrum. These results strengthen the utility of the beagle dog as a naturally occurring model of Alzheimer’s disease.
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