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Such covariation patterns of grey matter structure can be quantified as grey matter networks, which can be measured with magnetic resonance imaging. In Alzheimer\u2019s disease, the global organization of grey matter networks becomes more random, which is captured by a decline in the small-world coefficient. Such decline in the small-world value has been robustly associated with cognitive decline across clinical stages of Alzheimer\u2019s disease. The biological mechanisms causing this decline in small-world values remain unknown. Cerebrospinal fluid (CSF) protein biomarkers are available for studying diverse pathological mechanisms in humans and can provide insight into decline. We investigated the relationships between 10 CSF proteins and small-world coefficient in mutation carriers (N = 219) and non-carriers (N = 136) of the Dominantly Inherited Alzheimer Network Observational study. Abnormalities in Amyloid beta, Tau, synaptic (Synaptosome associated protein-25, Neurogranin) and neuronal calcium-sensor protein (Visinin-like protein-1) preceded loss of small-world coefficient by several years, while increased levels in CSF markers for inflammation (Chitinase-3-like protein 1) and axonal injury (Neurofilament light) co-occurred with decreasing small-world values. This suggests that axonal loss and inflammation play a role in structural grey matter network changes.<\/jats:p>","DOI":"10.1093\/braincomms\/fcae357","type":"journal-article","created":{"date-parts":[[2024,10,7]],"date-time":"2024-10-07T15:26:11Z","timestamp":1728314771000},"source":"Crossref","is-referenced-by-count":4,"title":["Axonal damage and inflammation response are biological correlates of decline in small-world values: a cohort study in autosomal dominant Alzheimer\u2019s disease"],"prefix":"10.1093","volume":"6","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7420-6384","authenticated-orcid":false,"given":"Lisa","family":"Vermunt","sequence":"first","affiliation":[{"name":"Alzheimer center Amsterdam, Department of Neurology, Amsterdam Neuroscience, Programme Neurodegeneration, Amsterdam University Medical Centers, Vrije Universiteit , 1081 HZ Amsterdam ,","place":["The Netherlands"]},{"name":"Neurochemistry Laboratory, Departmentt of Laboratory Medicine, Amsterdam 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