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The factors that account for this pattern of degeneration, including associated neuronal dysfunction and dysmorphia, are unclear. Previously, we generated a model of AD using the nematode Caenorhabditis elegans with the AD risk variant of apolipoprotein E (APOE4). We showed that the soma of HSN class neurons degenerate in early-adult animals. Here, we performed behavioral analyses to deduce the effect of APOE4 on the function of distinct neuronal circuits. We found evidence that APOE4 induces dysfunction of other neurons; this spatiotemporal pattern roughly correlates with endogenous levels of PTL-1, the C. elegans homolog of human MAPT, also known as tau. Moreover, deletion of ptl-1 suppressed defects in multiple behaviors, suggesting broad protective effects across the nervous system including the HSN neurons. Lastly, we showed that PTL-1 in the touch receptor neurons, in which PTL-1 is most abundant, contributes non-cell autonomously to age-related axon dysmorphia and dysfunction of the HSN neurons. Our results suggest that C. elegans provides a useful in vivo system to study how endogenous tau acts downstream of APOE4 to cause progressive, patterned neurodegenerative phenotypes.<\/jats:p>","DOI":"10.1242\/dmm.052469","type":"journal-article","created":{"date-parts":[[2026,6,11]],"date-time":"2026-06-11T07:57:17Z","timestamp":1781164637000},"source":"Crossref","is-referenced-by-count":1,"title":["Loss of endogenous tau suppresses APOE4-induced patterned behavioral decline and axon dysmorphia in a model of Alzheimer's disease"],"prefix":"10.1242","volume":"19","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8003-2691","authenticated-orcid":false,"given":"Eric A.","family":"Cardona","sequence":"first","affiliation":[{"name":"Center for Learning and Memory, University of Texas at Austin 1 Department of Neuroscience , , Austin, TX 78712 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7715-2278","authenticated-orcid":false,"given":"Chelsea J.","family":"Webber","sequence":"additional","affiliation":[{"name":"Center for Learning and Memory, University of Texas at Austin 1 Department of Neuroscience , , Austin, TX 78712 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zheng","family":"Wu","sequence":"additional","affiliation":[{"name":"Center for Learning and Memory, University of Texas at Austin 1 Department of Neuroscience , , Austin, TX 78712 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Blythe M.","family":"Bolton","sequence":"additional","affiliation":[{"name":"University of Texas at Austin 2 Department of Molecular Biosciences , , Austin, TX 78712 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8514-5505","authenticated-orcid":false,"given":"Elif","family":"Sarinay-Cenik","sequence":"additional","affiliation":[{"name":"University of Texas at Austin 2 Department of Molecular Biosciences , , Austin, TX 78712 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9619-4713","authenticated-orcid":false,"given":"Jonathan T.","family":"Pierce","sequence":"additional","affiliation":[{"name":"Center for Learning and Memory, University of Texas at Austin 1 Department of Neuroscience , , Austin, TX 78712 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"237","published-online":{"date-parts":[[2026,7,27]]},"reference":[{"key":"2026072703515589800_DMM052469C1","doi-asserted-by":"publisher","first-page":"13707","DOI":"10.1523\/JNEUROSCI.4040-10.2010","article-title":"Apolipoprotein E4 causes age- and Tau-dependent impairment of GABAergic interneurons, leading to learning and memory deficits in mice","volume":"30","author":"Andrews-Zwilling","year":"2010","journal-title":"J. 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