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This study leveraged positron emission tomography (PET) imaging to investigate the link between NFT accumulation and synaptic density in older adults with and without AD pathology.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>METHODS<\/jats:title>\n                    <jats:p>\n                      Older adults (\n                      <jats:italic>N\u00a0<\/jats:italic>\n                      =\u00a094) underwent PET imaging to quantify synaptic density ([\n                      <jats:sup>11<\/jats:sup>\n                      C]UCB\u2010J distribution volume ratio [DVR]), A\u03b2 plaque burden ([\n                      <jats:sup>11<\/jats:sup>\n                      C]PiB DVR), and NFT burden ([\n                      <jats:sup>18<\/jats:sup>\n                      F]MK\u20106240 standardized uptake value ratio). Analyses focused on NFT\u2010synaptic density correlations in the hippocampus (Hp) and entorhinal cortex (ERC), with additional subgroup analyses based on cognitive and A\u03b2 status.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>RESULTS<\/jats:title>\n                    <jats:p>Hp NFT burden strongly correlated with synaptic density, while the ERC showed weaker effects. Subgroup analyses found robust Hp associations in unimpaired AD participants.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>CONCLUSION<\/jats:title>\n                    <jats:p>Hippocampal synaptic density is highly vulnerable to early NFT accumulation. SV2A PET imaging enables early detection of synaptic loss and may also identify resilience to AD pathology.<\/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>Hippocampal synaptic density is similar in controls and unimpaired biologic AD.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>Hp synaptic density particularly vulnerable to Hp, ERC NFT burden.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>NFT\u2013synaptic density relationship may vary between unimpaired and impaired biologic AD<\/jats:p>\n                        <\/jats:list-item>\n                      <\/jats:list>\n       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