Retinal ganglion cell dendritic degeneration in a mouse model of Alzheimer's disease

Williams, Pete A., Thirgood, Rebecca A., Oliphant, Huw, Frizzati, Aura ORCID: https://orcid.org/0000-0002-7002-6180, Littlewood, Elinor, Votruba, Marcela ORCID: https://orcid.org/0000-0002-7680-9135, Good, Mark Andrew ORCID: https://orcid.org/0000-0002-1824-1203, Williams, Julie ORCID: https://orcid.org/0000-0002-4069-0259 and Morgan, James Edwards ORCID: https://orcid.org/0000-0002-8920-1065 2013. Retinal ganglion cell dendritic degeneration in a mouse model of Alzheimer's disease. Neurobiology of Aging 34 (7) , pp. 1799-1806. 10.1016/j.neurobiolaging.2013.01.006

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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.

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	MRC Centre for Neuropsychiatric Genetics and Genomics (CNGG) Medicine Neuroscience and Mental Health Research Institute (NMHRI) Optometry and Vision Sciences Psychology Systems Immunity Research Institute (SIURI)
Subjects:	R Medicine > RC Internal medicine > RC0321 Neuroscience. Biological psychiatry. Neuropsychiatry R Medicine > RE Ophthalmology
Uncontrolled Keywords:	Retinal ganglion cell; Dendrite; Synapse; Alzheimer's disease; Mitochondrion; Hippocampus
Publisher:	Elsevier
ISSN:	0197-4580
Last Modified:	10 Mar 2023 07:17
URI:	https://orca.cardiff.ac.uk/id/eprint/44783

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