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Preclinical studies suggest that apolipoprotein E4 (\n                      <jats:italic>APOE<\/jats:italic>\n                      4), a major genetic risk factor for Alzheimer's disease, may exacerbate glymphatic dysfunction\u2010related accumulation of beta\u2010amyloid (A\u03b2) and tau, but human evidence is lacking. This study examined whether\n                      <jats:italic>APOE<\/jats:italic>\n                      4 moderates the relationship between glymphatic dysfunction, estimated by the ALPS index, and A\u03b2 or tau deposition.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>METHODS<\/jats:title>\n                    <jats:p>\n                      We analyzed 423 older adults (mean age 70.5\u00a0\u00a0\u00b1\u00a0\u00a08.1 years) with varying cognitive profiles who underwent DTI to calculate the ALPS index and [\n                      <jats:sup>1<\/jats:sup>\n                      <jats:sup>1<\/jats:sup>\n                      C] Pittsburgh Compound B (PiB) positron emission tomography (PET) for A\u03b2 deposition. Additionally, 132 underwent [\n                      <jats:sup>1<\/jats:sup>\n                      \u2078F] AV\u20101451 PET for tau imaging.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>RESULTS<\/jats:title>\n                    <jats:p>\n                      A significant interaction between\n                      <jats:italic>APOE<\/jats:italic>\n                      4 status and ALPS index was observed for A\u03b2 deposition, but not for tau. A lower ALPS index was associated with higher A\u03b2 only in\n                      <jats:italic>APOE<\/jats:italic>\n                      4\u2010positive individuals.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>DISCUSSION<\/jats:title>\n                    <jats:p>\n                      <jats:italic>APOE<\/jats:italic>\n                      4 enhances the association between glymphatic dysfunction and A\u03b2 burden.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Highlights<\/jats:title>\n                    <jats:p>\n                      <jats:list list-type=\"bullet\">\n                        <jats:list-item>\n                          <jats:p>\n                            Apolipoprotein E4 (\n                            <jats:italic>APOE<\/jats:italic>\n                            4) status moderates the link between analysis along the perivascular space (ALPS) index and cerebral beta\u2010amyloid.\n                          <\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>\n                            Lower ALPS index is associated with higher beta\u2010amyloid (A\u03b2) only in\n                            <jats:italic>APOE<\/jats:italic>\n                            4 carriers.\n                          <\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>\n                            No significant moderation by\n                            <jats:italic>APOE<\/jats:italic>\n                            4 on ALPS\u2013tau association was found.\n                          <\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>ALPS index may offer non\u2010invasive glymphatic marker for beta\u2010amyloid burden.<\/jats:p>\n                        <\/jats:list-item>\n                      <\/jats:list>\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/alz.70837","type":"journal-article","created":{"date-parts":[[2025,10,29]],"date-time":"2025-10-29T04:01:51Z","timestamp":1761710511000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["APOE4 modulates the association between DTI\u2010ALPS index and Alzheimer's pathologies"],"prefix":"10.1002","volume":"21","author":[{"given":"Koung Mi","family":"Kang","sequence":"first","affiliation":[{"name":"Department of Radiology Seoul National University Hospital  Seoul Republic of Korea"},{"name":"Department of Radiology Seoul National University College of Medicine  Seoul Republic of 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