Relationship between topological efficiency of white matter structural connectome and plasma biomarkers across Alzheimer’s disease continuum

Introduction The associations between plasma AD biomarkers, brain network topology, and cognition across AD continuum remained unknown. Methods From the cohort of Sino Longitudinal Study of Cognitive Decline, we analyzed plasma biomarkers of 287 participants, including the levels of β-amyloid (Aβ), phosphorylated-tau181 (p-tau181), glial-fibrillary-acidic-protein (GFAP), and neurofilament-light-chain (NfL), and we assessed white matter network efficiency of 395 participants. Trend analyses evaluated the sensitivity of plasma markers and network efficiency with AD progression. Correlation and mediation analyses further explored the relationships among plasma markers, network efficiency, and cognition across AD continuum. Results Among the plasma markers, GFAP exhibited the highest sensitivity with AD progression, followed by NfL, p-tau18, and Aβ42/Aβ40. Local efficiency decreased in multiple brain regions and correlated with GFAP, NfL, and p-tau181. Network efficiency mediated the relationship between plasma markers and cognition. Discussion Our findings highlight the potential of network-plasma approaches for early detection and intervention of AD. ### Competing Interest Statement The authors have declared no competing interest. ### Funding Statement This study was supported by the Sino-German Cooperation Grant (M-0759); STI2030-Major Projects (2022ZD0213300, 2022ZD0211800); National Natural Science Foundation of China (82020108013, 82001773, 32271145, 81871425); Fundamental Research Funds for the Central Universities (2017XTCX04); Open Research Fund of the State Key Laboratory of Cognitive Neuroscience and Learning (CNLZD2101, CNLYB2001). ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: All participants or their legal guardians provided written informed consent. All procedures were approved by the Medical Research Ethics Committee and Institutional Review Board of Xuanwu Hospital. Cohorts are registered with [ClinicalTrials.gov][1] (SILCODE: [NCT02225964][2]). I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as [ClinicalTrials.gov][1]. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes All data produced in the present study are available upon reasonable request to the authors [1]: https://ClinicalTrials.gov [2]: /lookup/external-ref?link_type=CLINTRIALGOV&access_num=NCT02225964&atom=%2Fmedrxiv%2Fearly%2F2023%2F07%2F23%2F2023.07.21.23292999.atom