Retinal ganglion cell dendritic degeneration in a mouse model of Alzheimer's disease.
Document Type
Article
Publication Date
7-2013
JAX Source
Neurobiol Aging 2013 Jul; 34(7):1799-806.
Volume
34
Issue
7
First Page
1799
Last Page
1806
ISSN
1558-1497
PMID
23465714
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. Neurobiol Aging 2013 Jul; 34(7):1799-806.
Recommended Citation
Williams PA,
Thirgood R,
Oliphant H,
Frizzati A,
Littlewood E,
Votruba M,
Good M,
Williams J,
Morgan J.
Retinal ganglion cell dendritic degeneration in a mouse model of Alzheimer's disease. Neurobiol Aging 2013 Jul; 34(7):1799-806.