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The relationships among mGluR5 availability, tau deposition, and neuropsychological assessment were analyzed using Spearman's correlation and mediation analyses.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>RESULTS<\/jats:title>\n                    <jats:p>\n                      CI patients had lower mGluR5 in the hippocampus than CU (standardized uptake value ratio [SUVr]: 2.03\u00a0\u00b1\u00a00.25\u00a0vs 1.79\u00a0\u00b1\u00a00.17,\n                      <jats:italic>p<\/jats:italic>\n                      \u00a0=\u00a00.003). Hippocampal mGluR5 was negatively associated with hippocampal tau deposition (\n                      <jats:italic>r<\/jats:italic>\n                      \u00a0=\u00a0\u2212.46,\n                      <jats:italic>p<\/jats:italic>\n                      \u00a0=\u00a00.003) and positively associated with cognitive performance, but only in women. Hippocampal tau deposition mediated the effect of mGluR5 on cognitive performance.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>DISCUSSION<\/jats:title>\n                    <jats:p>Reduced hippocampal mGluR5 is negatively related with tau deposition in most cortical regions and positively associated with cognitive performance, making it a promising biomarker for AD diagnosis and therapy.<\/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>Cognitively impaired (CI) patients exhibited lower metabotropic glutamate receptor 5 (mGluR5) availability in the hippocampus than cognitively unimpaired (CU) subjects.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>Hippocampal mGluR5 availability was negatively associated with tau deposition in widespread cortex.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>Hippocampal mGluR5 availability was positively associated with cognitive performance.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>The close association of mGluR5 with tau and cognition performance exists only in females.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>Tau pathology mediated the relationship between mGluR5 availability and cognition.<\/jats:p>\n                        <\/jats:list-item>\n                      <\/jats:list>\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/alz.70004","type":"journal-article","created":{"date-parts":[[2025,2,26]],"date-time":"2025-02-26T03:56:38Z","timestamp":1740542198000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["Tau pathology is associated with postsynaptic metabotropic glutamate receptor 5 (mGluR5) in early Alzheimer's disease in a sex\u2010specific manner"],"prefix":"10.1002","volume":"21","author":[{"given":"Yan","family":"Wang","sequence":"first","affiliation":[{"name":"Department of Nuclear Medicine &amp; PET Center, Huashan Hospital Fudan University  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jie","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Nuclear Medicine &amp; PET Center, Huashan Hospital Fudan University  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xing","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Nuclear Medicine, Shanghai East Hospital Tongji University School of Medicine  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zengping","family":"Lin","sequence":"additional","affiliation":[{"name":"Central Research Institute United Imaging Health Care Group Co., Ltd.  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