title: Retinal ganglion cell dendritic degeneration in a mouse model of Alzheimer's disease.
abstract: 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.
authors: School of Optometry and Vision Sciences, Cardiff University, Cardiff, UK.
authors: Pete A
authors: PA
authors: Williams
authors: Rebecca A
authors: RA
authors: Thirgood
authors: Huw
authors: H
authors: Oliphant
authors: Aura
authors: A
authors: Frizzati
authors: Elinor
authors: E
authors: Littlewood
authors: Marcela
authors: M
authors: Votruba
authors: Mark A
authors: MA
authors: Good
authors: Julie
authors: J
authors: Williams
authors: James E
authors: JE
authors: Morgan
mesh_terms: D000544:Alzheimer Disease / Q000473:pathology*; D000818:Animals; D003712:Dendrites / Q000737:chemistry / Q000473:pathology* / Q000648:ultrastructure; D004195:Disease Models, Animal; D005260:Female; D051379:Mice; D008822:Mice, Transgenic; D012162:Retinal Degeneration / Q000473:pathology*; D012165:Retinal Ganglion Cells / Q000737:chemistry / Q000473:pathology* / Q000648:ultrastructure