Mari Aksnes

• Aksnes, Mari; Capogna, Elettra; Vidal-Piñeiro, Didac; Chaudhry, Farrukh Abbas; Myrstad, Marius & Idland, Ane-Victoria [Show all 13 contributors for this article] (2023). Matrix metalloproteinases are associated with brain atrophy in cognitively unimpaired individuals. Neurobiology of Aging. ISSN 0197-4580. 131, p. 11–23. doi: 10.1016/j.neurobiolaging.2023.05.012. Full text in Research Archive
• Knapskog, Anne Brita; Aksnes, Mari; Edwin, Trine Holt; Ueland, Per Magne; Ulvik, Arve & Fang, Fei [Show all 11 contributors for this article] (2023). Higher concentrations of kynurenic acid in CSF are associated with the slower clinical progression of Alzheimer's disease. Alzheimer's & Dementia. ISSN 1552-5260. 19(12), p. 5573–5582. doi: 10.1002/alz.13162. Full text in Research Archive
• Aksnes, Mari; Edwin, Trine Holt; Saltvedt, Ingvild Tina; Eldholm, Rannveig Sakshaug; Chaudhry, Farrukh Abbas & Halaas, Nathalie Bodd [Show all 9 contributors for this article] (2023). Sex-specific associations of matrix metalloproteinases in Alzheimer’s disease. Biology of Sex Differences. ISSN 2042-6410. 14(1). doi: 10.1186/s13293-023-00514-x. Full text in Research Archive
• Aksnes, Mari; Aass, Hans Christian Dalsbotten; Tiiman, Ann; Terenius, Lars; Bogdanovic, Nenad & Vukojević, Vladana [Show all 7 contributors for this article] (2022). Serum Amyloidogenic Nanoplaques and Cytokines in Alzheimer's Disease: Pilot Study in a Small Naturalistic Memory Clinic Cohort. Journal of Alzheimer's Disease. ISSN 1387-2877. 86(3), p. 1459–1470. doi: 10.3233/JAD-215504. Full text in Research Archive Show summary

  Background: Neuroinflammation is a central component of Alzheimer’s disease (AD) and correlates closely with amyloid pathology. Markers of inflammation such as cytokines, and amyloidogenic aggregates, so-called nanoplaques, are both promising biomarker candidates for AD. We have previously shown that there is a relationship between the levels of nanoplaques and cytokines in cerebrospinal fluid, but it is unknown whether this association extends to serum. Objective: Investigate in a naturalistic memory clinic cohort whether the associations between nanoplaques and cytokines in the cerebrospinal fluid extends to serum. Methods: We collected serum from 49 patients assessed for cognitive complaints at the Oslo University Hospital Memory Clinic (15 with clinical AD). We assessed the levels of serum nanoplaques with the novel Thioflavin-T fluorescence correlation spectroscopy (ThT-FCS) assay. Serum levels of nine cytokines (eotaxin-1, granulocyte colony-stimulating factor [G-CSF], interleukin [IL]-6, IL-7, IL-8, monocyte chemoattractant protein-1 (MCP-1), gamma induced protein 10 (IP-10), macrophage inflammatory protein [MIP]-1α, and MIP-1β) were quantified with a multiplex assay and read on a Luminex IS 200 instrument. Results: Serum nanoplaques were not increased in clinical AD patients compared to non-AD memory clinic patients and nanoplaques were not associated with any cytokines. The cytokines IL-8 and G-CSF were increased in patients with clinical AD compared to non-AD patients. Conclusion: In this small pilot study, serum nanoplaques were not associated with serum cytokines. Nanoplaque levels could not be used to separate clinical AD patients from non-AD patients in this unselected memory clinic cohort.

• Aksnes, Mari; Aass, Hans Christian Dalsbotten; Tiiman, Ann; Edwin, Trine Holt; Terenius, Lars & Bogdanovic, Nenad [Show all 8 contributors for this article] (2021). Associations of cerebrospinal fluid amyloidogenic nanoplaques with cytokines in Alzheimer's disease. Translational Neurodegeneration. ISSN 2096-6466. 10(1). doi: 10.1186/s40035-021-00244-3. Full text in Research Archive Show summary

  Background: The aggregation of amyloid β (Aβ) is central in the pathogenesis of Alzheimer's disease (AD). Recently it has been shown that specifically, larger, Thioflavin T-binding Aβ aggregates are associated with increased neuroinflammation and cytokine release. This study was aimed to quantify fibrillary amyloid aggregates, so-called nanoplaques, and investigate their relationship with cytokines in the cerebrospinal fluid (CSF). Methods: CSF was collected from 111 patients assessed for cognitive complaints at the Oslo University Hospital Memory Clinic. The patients were grouped based on their amyloid status. The CSF nanoplaque concentration was quantified with the Thioflavin T-fluorescence correlation spectroscopy (ThT-FCS) assay. The levels of nine cytokines (eotaxin-1, granulocyte stimulating factor, interleukin [IL]-6, IL-7, IL-8, monocyte chemoattractant protein-1, gamma-induced protein 10, macrophage inflammatory protein [MIP]-1α, and MIP-1β) were quantified with a magnetic bead-based multiplex assay and read on a Luminex IS 200 instrument. Results: There were 49 amyloid-negative and 62 amyloid-positive patients in the cohort; none of the cytokines differed significantly between the amyloid groups. The increased nanoplaque levels were associated with levels of MIP-1β below the lower limit of quantification, and with decreased levels of MIP-1α and IL-8. The associations remained significant when adjusted for age, sex, cognitive function, apolipoprotein ε4 status and CSF core biomarker levels. Conclusion: The cytokine levels were not associated with amyloid status in this cohort. The nanoplaque levels were negatively associated with MIP-1β, MIP-1α and IL-8, which is in line with recent findings suggesting that the upregulation of some cytokine markers has a protective role and is negatively associated with AD progression.

• Aksnes, Mari; Tiiman, Ann; Edwin, Trine Holt; Terenius, Lars; Bogdanovic, Nenad & Vukojevic, Vladana [Show all 7 contributors for this article] (2021). Comparison of cerebrospinal fluid amyloidogenic nanoplaques with core biomarkers of Alzheimer's disease. Frontiers in Aging Neuroscience. ISSN 1663-4365. 12:608628, p. 1–11. doi: 10.3389/fnagi.2020.608628. Full text in Research Archive
• Aksnes, Mari; Müller, Ebba Gløersen; Tiiman, Ann; Edwin, Trine Holt; Terenius, Lars & Rootwelt-Revheim, Mona-Elisabeth [Show all 9 contributors for this article] (2020). Amyloidogenic nanoplaques in cerebrospinal fluid: Relationship to amyloid brain uptake and clinical Alzheimer's disease in a memory clinic cohort. Journal of Alzheimer's Disease. ISSN 1387-2877. 77(2), p. 831–842. doi: 10.3233/JAD-200237. Full text in Research Archive Show summary

  Background: Aggregation of amyloid-β (Aβ) is an early pathological event in Alzheimer’s disease (AD). Consequently, measures of pathogenic aggregated Aβ are attractive biomarkers for AD. Here, we use a recently developed Thioflavin-T-Fluorescence Correlation Spectroscopy (ThT-FCS) assay to quantify structured ThT-responsive protein aggregates, so-called nanoplaques, in the cerebrospinal fluid (CSF). Objective: The overall aim of this work was to assess whether ThT-FCS determined CSF nanoplaque levels could predict amyloid brain uptake as determined by 18F-Flutemetamol PET analysis. Further, we assess whether nanoplaque levels could predict clinical AD. Methods: Nanoplaque levels in the CSF from 54 memory clinic patients were compared between sub-groups classified by 18F-Flutemetamol PET as amyloid-positive or amyloid-negative, and by clinical assessment as AD or non-AD. Results: Nanoplaque levels did not differ between amyloid groups and could not predict brain amyloid uptake. However, nanoplaque levels were significantly increased in patients with clinical AD, and were significant predictors for AD when adjusting for age, sex, cognitive function, and apolipoprotein E (APOE) genotype. Conclusion: The concentration of nanoplaques in the CSF differentiates patients with clinical AD from non-AD patients.

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