Retinal ganglion cell dendritic degeneration in a mouse model of Alzheimer's disease.
Neurobiol Aging 2013 Jul; 34(7):1799-806.
Retinal ganglion cells (RGCs) may be regarded as a target biomarker in Alzheimer's disease (AD). We therefore explored the possibility that RGC degeneration, rather than cell loss, is an early marker of neuronal degeneration in a murine model of AD. RGC dendritic morphology and dendritic spine densities of CA1 hippocampal pyramidal neurons were quantified in 14-month-old transgenic mice expressing the APP(SWE) (amyloid precusor protein-Swedish mutation) mutation (Tg2576). The dendritic integrity of RGCs was found to be significantly reduced in the absence of significant RGC loss in Tg2576 mice compared with age-matched wild-type controls. In hippocampal CA1 pyramidal neurons, we observed dendritic spines to be present at a lower frequency from the same animals, but this did not reach significance. Synaptic and mitochondrial protein expression markers (PSD95 [postsynaptic density protein 95], synaptophysin, and Mfn2 [mitofusin 2]) showed no significant changes in RGC synaptic densities but a highly significant change in mitochondrial morphology with a marked reduction in the integrity of the mitochondrial cristae. Our findings suggest that, in a well-characterized mouse model of AD, RGC dendritic atrophy precedes cell loss, and this change may be because of accumulations of amyloid-β. Because RGC dendrites are confined to the inner plexiform layer of the retina, imaging techniques that focus on this layer, rather than the loss of RGCs, may provide a sensitive biomarker for monitoring neural damage in AD. Neurobiol Aging 2013 Jul; 34(7):1799-806.
Williams, Pete A.; Thirgood, Rebecca A; Oliphant, Huw; Frizzati, Aura; Littlewood, Elinor; Votruba, Marcela; Good, Mark A; Williams, Julie; and Morgan, James E, "Retinal ganglion cell dendritic degeneration in a mouse model of Alzheimer's disease." (2013). Faculty Research 2013. 53.