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As a result, electrophysiology and plasma biomarkers are emerging as great candidates in this pursuit due to their low invasiveness. This is the first magnetoencephalography study to assess the relationship between minimum spanning tree parameters, an alternative to overcome the comparability and thresholding problem issues characteristic of conventional brain network analyses, and plasma phosphorylated tau231 levels in unimpaired individuals, with different risk levels of Alzheimer\u2019s disease. Seventy-six individuals with available magnetoencephalography recordings and phosphorylated tau231 plasma determination were included. The minimum spanning tree for the theta, alpha and beta bands for each subject was obtained, and the leaf fraction, tree hierarchy and diameter were calculated. To study the relationship between these topological parameters and phosphorylated tau231, we performed correlation analyses, for the whole sample and considering the two risk sub-groups separately. Increasing concentrations of phosphorylated tau231 were associated with greater leaf fraction and tree hierarchy values, along with lower diameter values, for the alpha and theta frequency bands. These results emerged for the whole sample and the higher risk group, but not for the lower risk group. Our results indicate that the network topology of cognitively unimpaired individuals with elevated plasma phosphorylated tau231 levels, a marker of Alzheimer\u2019s disease pathology and amyloid-\u03b2 accumulation, is already altered, shifting towards a more integrated network increasing its vulnerability and hub-dependency, mostly in the alpha band. This is indicated by increases in leaf fraction and tree hierarchy, along with reductions in diameter. These results match the initial trajectory proposed by theoretical models of disease progression and network disruption and suggest that changes in brain function and organization begin early on.<\/jats:p>","DOI":"10.1093\/braincomms\/fcae283","type":"journal-article","created":{"date-parts":[[2024,8,20]],"date-time":"2024-08-20T13:10:13Z","timestamp":1724159413000},"source":"Crossref","is-referenced-by-count":5,"title":["Minimum spanning tree analysis of unimpaired individuals at risk of Alzheimer\u2019s disease"],"prefix":"10.1093","volume":"6","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1817-6007","authenticated-orcid":false,"given":"Alejandra","family":"Garc\u00eda-Colomo","sequence":"first","affiliation":[{"name":"Center for Cognitive and Computational Neuroscience, Complutense University of Madrid , 28223 Pozuelo de Alarc\u00f3n ,","place":["Spain"]},{"name":"Department of Experimental Psychology, Cognitive Psychology and Speech and Language Therapy, Complutense University of Madrid , 28223 Pozuelo de Alarc\u00f3n ,","place":["Spain"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David","family":"L\u00f3pez-Sanz","sequence":"additional","affiliation":[{"name":"Department of Experimental Psychology, Cognitive Psychology and Speech and Language Therapy, Complutense University of Madrid , 28223 Pozuelo de Alarc\u00f3n ,","place":["Spain"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cornelis J","family":"Stam","sequence":"additional","affiliation":[{"name":"Department of Clinical Neurophysiology and Magnetoencephalography Center, Amsterdam Neuroscience, Amsterdam UMC, Vrije Universiteit Amsterdam , 1081 HV Amsterdam ,","place":["The Netherlands"]},{"name":"Amsterdam Neuroscience, Brain Imaging , 1081 HV Amsterdam ,","place":["The Netherlands"]},{"name":"Amsterdam Neuroscience, Systems and Network Neurosciences , 1081 HV Amsterdam ,","place":["The Netherlands"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Arjan","family":"Hillebrand","sequence":"additional","affiliation":[{"name":"Department of Clinical Neurophysiology and Magnetoencephalography Center, Amsterdam Neuroscience, Amsterdam UMC, Vrije Universiteit Amsterdam , 1081 HV Amsterdam ,","place":["The Netherlands"]},{"name":"Amsterdam Neuroscience, Brain Imaging , 1081 HV Amsterdam ,","place":["The Netherlands"]},{"name":"Amsterdam Neuroscience, Systems and Network Neurosciences , 1081 HV Amsterdam ,","place":["The Netherlands"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mart\u00edn","family":"Carrasco-G\u00f3mez","sequence":"additional","affiliation":[{"name":"Center for Cognitive and Computational Neuroscience, Complutense University of Madrid , 28223 Pozuelo de Alarc\u00f3n ,","place":["Spain"]},{"name":"Department of Electronic Engineering, Universidad Polit\u00e9cnica de Madrid , 28040 Madrid ,","place":["Spain"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Carlos","family":"Spuch","sequence":"additional","affiliation":[{"name":"Translational Neuroscience Research Group, Galicia Sur Health Research Institute (IIS-Galicia Sur), SERGAS-UVIGO, CIBERSAM , 36312 Vigo ,","place":["Spain"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mar\u00eda","family":"Comis-Tuche","sequence":"additional","affiliation":[{"name":"Translational Neuroscience Research Group, Galicia Sur Health Research Institute (IIS-Galicia Sur), SERGAS-UVIGO, CIBERSAM , 36312 Vigo ,","place":["Spain"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fernando","family":"Maest\u00fa","sequence":"additional","affiliation":[{"name":"Center for Cognitive and Computational Neuroscience, Complutense University of Madrid , 28223 Pozuelo de Alarc\u00f3n ,","place":["Spain"]},{"name":"Department of Experimental Psychology, Cognitive Psychology and Speech and Language 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