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Pathological tau propagates through the AD brain in a defined manner, which correlates with neuron and synapse loss and cognitive decline. One proposed mechanism of tau spread is through synaptically connected brain structures. Apolipoprotein E4 ( APOE4) genotype is the strongest genetic risk factor for late-onset AD and is associated with increased tau burden. Whether the apolipoprotein E ( APOE) genotype influences neurodegeneration via tau spread is currently unknown. Here, we demonstrate that virally expressed human tau (with the P301L mutation) injected into mouse entorhinal cortex at 5\u20136\u2009months or 15\u201316\u2009months of age spreads trans-synaptically to the hippocampus by 14\u2009weeks post-injection. Injections of tau in mice expressing human APOE2, APOE3 or APOE4, as well as APOE knock-outs, showed that tau can spread trans-synaptically in all genotypes and that APOE genotype and age do not affect the spread of tau. These data suggest that APOE genotype is not directly linked to synaptic spread of tau in our model, but other mechanisms involving non-cell autonomous manners of tau spread are still possible.<\/jats:p>","DOI":"10.1177\/23982128231191046","type":"journal-article","created":{"date-parts":[[2023,8,17]],"date-time":"2023-08-17T03:15:35Z","timestamp":1692242135000},"update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":13,"title":["Apolipoprotein E isoform does not influence trans-synaptic spread of tau pathology in a mouse model"],"prefix":"10.1177","volume":"7","author":[{"given":"Caitlin","family":"Davies","sequence":"first","affiliation":[{"name":"Centre for Discovery Brain Sciences and UK Dementia Research Institute, The University of Edinburgh, Edinburgh, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jane","family":"Tulloch","sequence":"additional","affiliation":[{"name":"Centre for Discovery Brain 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