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Differences in hippocampal [\n                      <jats:sup>11<\/jats:sup>\n                      C]UCB\u2010J SUVRs were analyzed with analysis of variance (ANOVA) and linear models. Associations among [\n                      <jats:sup>11<\/jats:sup>\n                      C]UCB\u2010J SUVR, A\u03b2, hippocampal volume, and cognitive variables were analyzed with Spearman correlation.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>RESULTS<\/jats:title>\n                    <jats:p>\n                      Hippocampal synaptic density was different among the\n                      <jats:italic>APOE<\/jats:italic>\n                      groups (\n                      <jats:italic>P<\/jats:italic>\n                      <jats:sub>ANOVA\u00a0<\/jats:sub>\n                      =\u00a00.016):\n                      <jats:italic>APOE<\/jats:italic>\n                      \u03b54\/\u03b54 carriers had lower [\n                      <jats:sup>11<\/jats:sup>\n                      C]UCB\u2010J SUVRs compared to\n                      <jats:italic>APOE<\/jats:italic>\n                      \u03b53\/\u03b53 (\n                      <jats:italic>p\u00a0<\/jats:italic>\n                      =\u00a00.013). Hippocampal synaptic density did not correlate with Consortium to Establish a Registry for Alzheimer's Disease (CERAD) total score (rho\u00a0=\u00a0\u22120.052,\n                      <jats:italic>p\u00a0<\/jats:italic>\n                      =\u00a00.74), Alzheimer's Prevention Initiative Preclinical Cognitive Composite (APCC) score (rho\u00a0=\u00a00.17,\n                      <jats:italic>p\u00a0<\/jats:italic>\n                      =\u00a00.28), or [\n                      <jats:sup>11<\/jats:sup>\n                      C]PiB uptake (rho\u00a0=\u00a0\u22120.10,\n                      <jats:italic>p<\/jats:italic>\n                      \u00a0=\u00a00.50).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>DISCUSSION<\/jats:title>\n                    <jats:p>Hippocampal synaptic loss emerges early in the AD continuum and is measurable in vivo in cognitively unimpaired high\u2010risk individuals.<\/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                            Synaptic density was studied in vivo in healthy older adults using [\n                            <jats:sup>11<\/jats:sup>\n                            C]UCB\u2010J positron emission tomography.\n                          <\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>\n                            Apolipoprotein E (\n                            <jats:italic>APOE<\/jats:italic>\n                            ) \u03b54\/\u03b54 carriers had lower hippocampal synaptic density compared to\n                            <jats:italic>APOE<\/jats:italic>\n                            \u03b53\/\u03b53.\n                          <\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>Synaptic density was not associated with cognitive performance in this population.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>\n                            Hippocampal synaptic alterations occur before clinical symptoms in\n                            <jats:italic>APOE<\/jats:italic>\n                            \u03b54\/\u03b54 carriers.\n                          <\/jats:p>\n                        <\/jats:list-item>\n                      <\/jats:list>\n                    <\/jats:p>\n                  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