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Dementia"],"published-print":{"date-parts":[[2025,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>INTRODUCTION<\/jats:title>\n                    <jats:p>\n                      Elevated plasma homocysteine (Hcy) is associated with an increased risk of developing neurodegenerative diseases; however, its relationship with the apolipoprotein E (\n                      <jats:italic>APOE<\/jats:italic>\n                      ) \u03b54 allele has not been well characterized.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>METHODS<\/jats:title>\n                    <jats:p>\n                      Participants clinically diagnosed with Alzheimer's disease or mild cognitive impairment (AD\/MCI), frontotemporal dementia, Parkinson's disease, or cerebrovascular disease were stratified by the presence of the\n                      <jats:italic>APOE<\/jats:italic>\n                      \u03b54 allele. Volumetric magnetic resonance imaging, plasma amyloid\/tau\/neurodegeneration biomarkers, and cognitive performance were quantified.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>RESULTS<\/jats:title>\n                    <jats:p>\n                      Across all diagnostic groups, Hcy was associated with lower brain parenchymal fraction and greater neurofilament light chain in\n                      <jats:italic>APOE<\/jats:italic>\n                      \u03b54 non\u2010carriers only. In AD\/MCI, Hcy was associated with phosphorylated tau 217 in\n                      <jats:italic>APOE<\/jats:italic>\n                      \u03b54 non\u2010carriers, but not in carriers. Exploratory analyses revealed interactions between Hcy and\n                      <jats:italic>APOE<\/jats:italic>\n                      \u03b54 on memory and visuospatial function.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>DISCUSSION<\/jats:title>\n                    <jats:p>\n                      Hcy may contribute to neurodegeneration depending on the presence of the\n                      <jats:italic>APOE<\/jats:italic>\n                      \u03b54 allele and specific disease processes. Trials on vitamin B12 supplementation may consider stratifying by\n                      <jats:italic>APOE<\/jats:italic>\n                      genotype.\n                    <\/jats:p>\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>Homocysteine (Hcy) was associated with neurodegenerative biomarkers across disease groups.<\/jats:p>\n                          <\/jats:list-item>\n                          <jats:list-item>\n                            <jats:p>\n                              Relationships with Hcy were predominantly found in apolipoprotein E (\n                              <jats:italic>APOE<\/jats:italic>\n                              ) \u03b54 non\u2010carriers.\n                            <\/jats:p>\n                          <\/jats:list-item>\n                          <jats:list-item>\n                            <jats:p>\n                              In Alzheimer's disease, associations between Hcy and phosphorylated tau 217 were found in\n                              <jats:italic>APOE<\/jats:italic>\n                              \u03b54 non\u2010carriers only.\n                            <\/jats:p>\n                          <\/jats:list-item>\n                          <jats:list-item>\n                            <jats:p>\n                              Significant interactions existed between Hcy and\n                              <jats:italic>APOE<\/jats:italic>\n                              \u03b54 status on cognition.\n                            <\/jats:p>\n                          <\/jats:list-item>\n                        <\/jats:list>\n                      <\/jats:p>\n                    <\/jats:sec>\n                  <\/jats:sec>","DOI":"10.1002\/alz.14376","type":"journal-article","created":{"date-parts":[[2024,11,19]],"date-time":"2024-11-19T04:54:34Z","timestamp":1731992074000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Homocysteine, neurodegenerative biomarkers, and\n                    <i>APOE<\/i>\n                    \u03b54 in neurodegenerative diseases"],"prefix":"10.1002","volume":"21","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3610-5213","authenticated-orcid":false,"given":"William Z.","family":"Lin","sequence":"first","affiliation":[{"name":"Department of Pharmacology &amp; 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