Browsing by Author "Sutphen, Courtney L."

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    Associations among plasma, MRI, and amyloid PET biomarkers of Alzheimer's disease and related dementias and the impact of health‐related comorbidities in a community‐dwelling cohort
    (Wiley, 2024) Rudolph, Marc D.; Sutphen, Courtney L.; Register, Thomas C.; Whitlow, Christopher T.; Solingapuram Sai, Kiran K.; Hughes, Timothy M.; Bateman, James R.; Dage, Jeffrey L.; Russ, Kristen A.; Mielke, Michelle M.; Craft, Suzanne; Lockhart, Samuel N.; Neurology, School of Medicine
    Introduction: We evaluated associations between plasma and neuroimaging-derived biomarkers of Alzheimer's disease and related dementias and the impact of health-related comorbidities. Methods: We examined plasma biomarkers (neurofilament light chain, glial fibrillary acidic protein, amyloid beta [Aβ] 42/40, phosphorylated tau 181) and neuroimaging measures of amyloid deposition (Aβ-positron emission tomography [PET]), total brain volume, white matter hyperintensity volume, diffusion-weighted fractional anisotropy, and neurite orientation dispersion and density imaging free water. Participants were adjudicated as cognitively unimpaired (CU; N = 299), mild cognitive impairment (MCI; N = 192), or dementia (DEM; N = 65). Biomarkers were compared across groups stratified by diagnosis, sex, race, and APOE ε4 carrier status. General linear models examined plasma-imaging associations before and after adjusting for demographics (age, sex, race, education), APOE ε4 status, medications, diagnosis, and other factors (estimated glomerular filtration rate [eGFR], body mass index [BMI]). Results: Plasma biomarkers differed across diagnostic groups (DEM > MCI > CU), were altered in Aβ-PET-positive individuals, and were associated with poorer brain health and kidney function. Discussion: eGFR and BMI did not substantially impact associations between plasma and neuroimaging biomarkers. Highlights: Plasma biomarkers differ across diagnostic groups (DEM > MCI > CU) and are altered in Aβ-PET-positive individuals. Altered plasma biomarker levels are associated with poorer brain health and kidney function. Plasma and neuroimaging biomarker associations are largely independent of comorbidities.
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    Axonal damage and inflammation response are biological correlates of decline in small-world values: a cohort study in autosomal dominant Alzheimer's disease
    (Oxford University Press, 2024-10-09) Vermunt, Lisa; Sutphen, Courtney L.; Dicks, Ellen; de Leeuw, Diederick M.; Allegri, Ricardo F.; Berman, Sarah B.; Cash, David M.; Chhatwal, Jasmeer P.; Cruchaga, Carlos; Day, Gregory S.; Ewers, Michael; Farlow, Martin R.; Fox, Nick C.; Ghetti, Bernardino; Graff-Radford, Neill R.; Hassenstab, Jason; Jucker, Mathias; Karch, Celeste M.; Kuhle, Jens; Laske, Christoph; Levin, Johannes; Masters, Colin L.; McDade, Eric; Mori, Hiroshi; Morris, John C.; Perrin, Richard J.; Preische, Oliver; Schofield, Peter R.; Suárez-Calvet, Marc; Xiong, Chengjie; Scheltens, Philip; Teunissen, Charlotte E.; Visser, Pieter Jelle; Bateman, Randall J.; Benzinger, Tammie L. S.; Fagan, Anne M.; Gordon, Brian A.; Tijms, Betty M.; Pathology and Laboratory Medicine, School of Medicine
    The grey matter of the brain develops and declines in coordinated patterns during the lifespan. Such covariation patterns of grey matter structure can be quantified as grey matter networks, which can be measured with magnetic resonance imaging. In Alzheimer's 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's 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.