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In addition to brain pathology, amyloid plaque deposition, microglial activation, and cell loss occur in the retinas of human patients and animal models of Alzheimer\u2019s disease. Retinal ganglion cells, the output neurons of the retina, are vulnerable to damage in neurodegenerative diseases and are a potential opportunity for non-invasive clinical diagnosis and monitoring of Alzheimer\u2019s progression. However, the extent of retinal involvement in Alzheimer\u2019s models and how well this reflects brain pathology is unclear. Here we have quantified changes in retinal ganglion cells dendritic structure and hippocampal dendritic spines in three well-studied Alzheimer\u2019s mouse models, Tg2576, 3xTg-AD and APP<jats:sup>NL-G-F<\/jats:sup>. Dendritic complexity of DiOlistically labelled retinal ganglion cells from retinal explants was reduced in all three models in an age-, gender-, and receptive field-dependent manner. DiOlistically labelled hippocampal slices showed spine loss in CA1 apical dendrites in all three Alzheimer\u2019s models, mirroring the early stages of neurodegeneration as seen in the retina. Morphological classification showed that loss of thin spines predominated in all. The demonstration that retinal ganglion cells dendritic field reduction occurs in parallel with hippocampal dendritic spine loss in all three Alzheimer\u2019s models provide compelling support for the use of retinal neurodegeneration. As retinal dendritic changes are within the optical range of current clinical imaging systems (for example optical coherence tomography), our study makes a case for imaging the retina as a non-invasive way to diagnose disease and monitor progression in Alzheimer\u2019s disease.<\/jats:p>","DOI":"10.1186\/s40478-020-01094-2","type":"journal-article","created":{"date-parts":[[2020,12,7]],"date-time":"2020-12-07T10:05:56Z","timestamp":1607335556000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":45,"title":["Retinal ganglion cell degeneration correlates with hippocampal spine loss in experimental Alzheimer\u2019s disease"],"prefix":"10.1186","volume":"8","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2557-2887","authenticated-orcid":false,"given":"Ryan J.","family":"Bevan","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2348-3490","authenticated-orcid":false,"given":"Tim R.","family":"Hughes","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6194-8397","authenticated-orcid":false,"given":"Pete A.","family":"Williams","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1824-1203","authenticated-orcid":false,"given":"Mark A.","family":"Good","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4075-7676","authenticated-orcid":false,"given":"B. 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