{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,9,4]],"date-time":"2026-09-04T21:14:28Z","timestamp":1788556468839,"version":"build-2803163510"},"posted":{"date-parts":[[2025,10,3]]},"group-title":"Neuroscience","reference-count":0,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2025,10,3]],"date-time":"2025-10-03T00:00:00Z","timestamp":1759449600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2026,9,4]]},"abstract":"<jats:p>The spatial distribution of tau pathology, a key correlate of neurodegeneration and cognitive decline in Alzheimer's disease (AD), varies markedly across individuals. While tau is thought to spread along brain networks, the role of inter-individual variability in accounting for these patterns remains underexplored. Using resting-state fMRI and tau-PET from 805 BioFINDER participants across the AD continuum, with replication in ADNI (n=361) and A4 (n=336), we studied whether subject-specific functional connectivity (FC) profiles enhance the characterization of tau deposition patterns. A hybrid approach integrating individual and group-average FC explained individual tau-PET topographies better than either FC representation alone, particularly in symptomatic individuals and at finer spatial resolutions. Hybrid FC also better captured individual tau topographies than canonical tau-PET maps derived from cohort-level data. These effects were specific to tau and not similarly observed for \u03b2-amyloid, and the explanatory advantage of FC-based models increased with spatial granularity. Furthermore, baseline hybrid FC explained follow-up tau-PET topography better than template FC, suggesting that individualized baseline connectivity contains information about future tau-PET progression. The main FC model-comparison findings replicated in ADNI and A4. Collectively, these findings show that individual functional brain architecture is associated with heterogeneity in tau-PET topography. While not establishing a causal propagation mechanism, our findings are consistent with network-spread models. This work advances the methodological characterization of tau-PET heterogeneity in AD and highlights functional connectivity as a potentially informative marker of individual tau-PET trajectories.<\/jats:p>","DOI":"10.1101\/2025.10.02.679969","type":"posted-content","created":{"date-parts":[[2025,10,4]],"date-time":"2025-10-04T00:45:24Z","timestamp":1759538724000},"source":"Crossref","is-referenced-by-count":2,"title":["Patient-specific functional brain architecture explains cortical patterns of tau PET in Alzheimer's disease"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6729-6801","authenticated-orcid":false,"given":"Harry H","family":"Behjat","sequence":"first","affiliation":[{"name":"Lund University;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6394-9940","authenticated-orcid":false,"given":"Jacob W","family":"Vogel","sequence":"additional","affiliation":[{"name":"Lund 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