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These processes include lipid metabolism potentially regulated upstream by Apolipoprotein E (APOE) and clearance of APOE itself.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>\n                      To determine the impact of HTT reduction on autophagy and clearance of APOE in cell culture and in mouse liver\n                      <jats:italic toggle=\"yes\">in vivo<\/jats:italic>\n                      .\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Western blot analysis was performed on liver tissue from tamoxifen-treated mice with and without UBC-Cre expression, required for tamoxifen-induced HTT knockout (KO). siRNA was used to knockdown (KD) HTT in HepG2 immortalized liver cells.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>HTT KO in mouse liver reduces levels of LAMP2A, a protein essential for chaperone-mediated autophagy (CMA) which we previously found is required for optimal degradation of APOE and HTT in cultured cells. In turn, APOE levels were increased with HTT KO in mouse liver, while HTT KD in cell culture decreased levels of APOE.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>In the context of liver tissue, reduced CMA may contribute to accumulation of APOE and autophagic cargo resulting from a loss of HTT function in autophagy. The extent to which macroautophagy is upregulated to cope with reduced CMA found with HTT KO may be tissue specific, which may relate to the selectivity of tissue pathogenesis observed in Huntington's disease where loss of normal HTT function may be involved. This study may help elucidate the consequences of systemic HTT reduction on autophagy in liver tissue.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1177\/18796397251391110","type":"journal-article","created":{"date-parts":[[2025,10,29]],"date-time":"2025-10-29T17:11:46Z","timestamp":1761757906000},"page":"110-123","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":0,"title":["Huntingtin knockdown dysregulates autophagic degradation of Apolipoprotein E"],"prefix":"10.1177","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1854-7894","authenticated-orcid":false,"given":"Gianna M","family":"Fote","sequence":"first","affiliation":[{"name":"Department of Biological Chemistry, University of California Irvine, Irvine, CA, USA"},{"name":"Department of Neurological Surgery, University of California Irvine, Irvine, CA, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3251-1441","authenticated-orcid":false,"given":"Nicolette R","family":"McClure","sequence":"additional","affiliation":[{"name":"Department of Neurobiology and Behavior, University of California Irvine, Irvine, CA, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0619-8954","authenticated-orcid":false,"given":"Robert M","family":"Bragg","sequence":"additional","affiliation":[{"name":"University of Washington"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3533-1753","authenticated-orcid":false,"given":"Jharrayne","family":"McKnight","sequence":"additional","affiliation":[{"name":"Department of Neurobiology and Behavior, University of California Irvine, Irvine, CA, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4573-9514","authenticated-orcid":false,"given":"Leslie M","family":"Thompson","sequence":"additional","affiliation":[{"name":"Department of Biological Chemistry, University of California Irvine, Irvine, CA, USA"},{"name":"Department of Neurobiology and Behavior, University of California Irvine, Irvine, CA, USA"},{"name":"Department of Psychiatry and Human Behavior, University of California Irvine, Irvine, CA, USA"},{"name":"Institute for Memory Impairments and Neurological Disorders, University of California Irvine, Irvine, CA, USA"},{"name":"Center for Epigenetics and Metabolism, University of California Irvine, Irvine, CA, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1711-8868","authenticated-orcid":false,"given":"Jeffrey B","family":"Carroll","sequence":"additional","affiliation":[{"name":"University of Washington"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2467-6294","authenticated-orcid":false,"given":"Joan S","family":"Steffan","sequence":"additional","affiliation":[{"name":"Department of Psychiatry and Human Behavior, University of California Irvine, Irvine, CA, USA"},{"name":"Institute for Memory Impairments and Neurological Disorders, University of California Irvine, Irvine, CA, USA"},{"name":"Center for Epigenetics and Metabolism, University of California Irvine, Irvine, CA, 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