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However, those brain properties underlying the region\u2010dependent susceptibility to tau accumulation remain unclear.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>METHODS<\/jats:title>\n                    <jats:p>We constructed multimodal spatial gradients to characterize molecular properties and connectomic architecture. A predictive model for regional tau deposition was developed by integrating embeddings in the principal gradients of global connectome gradients with gene expression, neurotransmitters, myelin, and amyloid\u2010beta. The model was trained on amyloid\u2010beta\u2013positive participants from Alzheimer's Disease Neuroimaging Initiative (ADNI) and externally validated in independent datasets.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>RESULTS<\/jats:title>\n                    <jats:p>The combination of gradients explained up to 77.7% of cross\u2010sectional and 77.3% of longitudinal inter\u2010regional variance of tau deposition. Gene set enrichment analysis of a major gene expression gradient points to synaptic transmission to confer increased susceptibility to tau.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>DISCUSSION<\/jats:title>\n                    <jats:p>Our findings reveal a spatially heterogeneous molecular landscape shaping regional susceptibility to tau deposition, presenting a powerful system\u2010level explanatory model of tau pathology in AD.<\/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>Spatial gradients of fundamental molecular brain properties associated with tau pathology.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>The explanatory power showed high consistency across studies.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>Genetic analyses suggested that synapse expression plays a vital role in tau accumulation.<\/jats:p>\n                        <\/jats:list-item>\n                      <\/jats:list>\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/alz.70170","type":"journal-article","created":{"date-parts":[[2025,5,8]],"date-time":"2025-05-08T07:45:26Z","timestamp":1746690326000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Multimodal spatial gradients to explain regional susceptibility to fibrillar tau in Alzheimer's disease"],"prefix":"10.1002","volume":"21","author":[{"given":"Ying","family":"Luan","sequence":"first","affiliation":[{"name":"Department of Radiology Zhongda Hospital, School of 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