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Marcela Votruba, Pete A. Williams, Rebecca A. Thirgood, Huw Oliphant, Mark A. Good, Julie Williams, James E. Morgan; Retinal Ganglion Cell Dendritic Degeneration in a Mouse Model Of Alzheimer’s Disease. Invest. Ophthalmol. Vis. Sci. 2012;53(14):4650. doi: https://doi.org/.
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© ARVO (1962-2015); The Authors (2016-present)
Retinal ganglion cells (RGC) may be regarded as a target biomarker in Alzheimer’s disease (AD). The retina is the only organ in which neurons can be imaged on a repeatable and long terms basis. We explored the possibility that RGC degeneration rather than cell death is an early marker of neuronal degeneration in a murine model of AD.
RGC dendritic morphology was assessed in retinal flat mounts and dendritic spine densities of CA1 hippocampal pyramidal neurones were quantified in 14 month old female transgenic mice expressing the APP (Swe) mutation (Tg2576) (Tg; n= 9: WT; n=8). Cells were labelled diolistically using DiI coated tungsten particles. Analysis of dendritic field area and dendritic length was carried out using ImageJ and NeuronJ respectively, and a custom Matlab macro to run a Sholl analysis, to assess dendritic complexity.
We observed a significant, 34.4% reduction in dendritic field area (±SEM) (WT, 33680±2034µm²; Tg2576, 22083±11573µm²; P = 0.0001) for retinal ganglion cells from Tg animals. Consistent with this, total dendritic length was reduced by 32.4% in Tg animals (±SEM) (WT, 1589±95µm; Tg, 1074±99µm; P = 0.0001). The Sholl plot confirmed a significant reduction in dendritic complexity for mid to peripheral parts of the dendritic tree. For hippocampal CA1 pyramidal neurones we assessed 2613 spines from 124 dendrites in Tg2576 animals and 3958 spines from 185 dendrites in WT animals. Although we observed a general trend for the number of spines to be reduced in the TG animals this did not reach conventional levels of significance (spines/µm±SEM; WT, 0.2679±0.0086; Tg, 0.2490±0.0076; Reduction, -7.1%; P = 0.05).
Our findings suggest that, in a well characterised mouse model of AD, RGC dendritic atrophy precedes RGC loss and, crucially, may precede dendritic spine changes in the hippocampus. Since RGC dendrites are confined to the inner plexiform layer of the retina, imaging techniques that focus on this layer, rather than the loss of retinal ganglion cells, may provide a new sensitive early biomarker for monitoring neural damage in AD.
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