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We hypothesized that dysfunction primarily emerges in regions close to tau\u2010harboring epicenters.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>METHODS<\/jats:title>\n                    <jats:p>\n                      One hundred thirty\u2010one amyloid\u2010positive individuals underwent dynamic [\n                      <jats:sup>18<\/jats:sup>\n                      F]PI\u20102620 tau positron emission tomography. Kinetic modeling yielded distribution volume ratios (DVRs) and perfusion (R1). Tau epicenters were defined as top 10% DVR regions. Connectivity\u2010based distance to epicenters was derived from normative resting\u2010state functional connectivity.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>RESULTS<\/jats:title>\n                    <jats:p>At the individual level, hypoperfusion was more closely related to distance from tau epicenters than to local tau deposition, particularly in early AD, consistent with diaschisis\u2010like disconnection. With advancing biological disease severity, local tau deposition increasingly converged with hypoperfusion. Critically, hypoperfusion mediated the relationship between tau accumulation and cognitive decline.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>DISCUSSION<\/jats:title>\n                    <jats:p>Tau epicenters shape the brain\u2010wide pattern of neuronal dysfunction, while local tau burden determines the degree of damage driving cognitive decline.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/alz.71914","type":"journal-article","created":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T16:19:05Z","timestamp":1791389945000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Network\u2010dependent remote effects and local tau burden jointly shape neuronal dysfunction in Alzheimer's 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