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L. Guo, S. Nizari, E. M. Normando, S. Sensi, M. F. Cordeiro; Amyloid-ß and Tau Pathology in the Retina of a Triple-Transgenic Model of Alzheimer’s Disease (3xTg-AD). Invest. Ophthalmol. Vis. Sci. 2010;51(13):2113.
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Amyloid-ß (Aß) deposition and tau pathology in the brain are hallmarks of Alzheimer’s disease (AD), and recent studies have shown that similar pathological changes are also seen in the retina. However, there has been no previous investigation of retinal involvement in triple-transgenic (3xTg) AD mice that harbour three mutations of human APP (Swedish mutation), tau (P301L mutation) and presenilin (PS)-1 knockin, and mimic many critical aspects of AD neuropathology, including Aß plaques and neurofibrillary tangles development in the brain. The aim of this study was to examine Alzheimer’s related pathology in 3xTg-AD eyes including retina, lens and cornea..
Four eyes from the 3xTg-AD mice aged 14 months and two eyes from control mice aged 18 months were killed for immunohistochemistry. Whole eyes were embedded in paraffin after fixation in 4% fresh paraformaldehyde. Paraffin cross-sections of eyes were immunostained for Alzheimer’s related pathology, using antibodies against Aß (abcam 68896), APP (abcam 2084) and PHF-tau (AT8, Source BioScience). Retina, lens and corneal sections were graded by masked observers using a well-established method.
The eyes from 3xTg-AD mice showed overall an increase in both Aß and hyperphosphorylated tau (p-tau) compared to controls. In AD mice, increased Aß deposition was clearly visualized in the retina, associated with both intraneuronal and extraneuronal accumulation in retinal ganglion cells (RGCs) and the inner segments of photoreceptors. Over-expression of p-tau was evidenced across the retina. Substantial increase of both Aß and p-tau immunostaining was also found in the lens nucleus in AD mice compared to controls. In addition, Aß and p-tau immunostaining was observed in the cornea, especially in the corneal epithelium of AD mice.
This is the first demonstration of abnormal expression of Aß and hyper phosphorylated tau in the retina and lens in 3xTg-AD mice. Our results provide evidence that similar mechanisms of neurodegeneration in the brain occur in the eye, particularly in the retina in AD. The findings strengthen the notion of the eye being used as a window onto the brain in this disease.
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