Nathalie Bodd Halaas

• Titlestad, Irit; Watne, Leiv; Caplan, Gideon A.; McCann, Adrian; Ueland, Per Magne & Neerland, Bjørn Erik [Show all 15 contributors for this article] (2023). Impaired glucose utilization in the brain of patients with delirium following hip fracture. Brain. ISSN 0006-8950. 147(1), p. 215–223. doi: 10.1093/brain/awad296. Full text in Research Archive
• 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
• Capogna, Elettra; Watne, Leiv; Sørensen, Øystein; Guichelaar, Carlijn Jamila; Idland, Ane-Victoria & Halaas, Nathalie Bodd [Show all 11 contributors for this article] (2023). Associations of neuroinflammatory IL-6 and IL-8 with brain atrophy, memory decline, and core AD biomarkers – in cognitively unimpaired older adults. Brain, Behavior, and Immunity. ISSN 0889-1591. 113, p. 56–65. doi: 10.1016/j.bbi.2023.06.027. 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
• Watne, Leiv Otto; Pollmann, Christian Thomas; Neerland, Bjørn Erik; Paulsen, Else Quist; Halaas, Nathalie Bodd & Idland, Ane-Victoria [Show all 19 contributors for this article] (2022). Cerebrospinal fluid quinolinic acid is strongly associated with delirium and mortality in hip-fracture patients. Journal of Clinical Investigation. ISSN 0021-9738. 133(2). doi: 10.1172/JCI163472. Full text in Research Archive Show summary

  Background: The kynurenine pathway (KP) has been identified as a potential mediator linking acute illness to cognitive dysfunction by generating neuroactive metabolites in response to inflammation. Delirium (acute confusion) is a common complication of acute illness and is associated with increased risk of dementia and mortality. However, the molecular mechanism underlying delirium, particularly in relation to the KP, remain elusive. Methods: We undertook a multi-center observational study with 586 hospitalized patients (248 with delirium) and investigated associations between delirium and KP metabolites measured in cerebrospinal fluid (CSF) and serum by targeted metabolomics. We also explored associations between KP metabolites and markers of neuronal damage and one-year mortality. Results: In delirium, we found concentrations of the neurotoxic metabolite quinolinic acid in CSF (CSF-QA, OR 2.26 [1.78, 2.87], p

• Solvang, Stein-Erik Hafstad; Hodge, Allison; Watne, Leiv; Cabral-Marques, Otavio; Nordrehaug, Jan Erik & Giles, Graham G. [Show all 16 contributors for this article] (2022). Kynurenine Pathway Metabolites in the Blood and Cerebrospinal Fluid Are Associated with Human Aging. Oxidative Medicine and Cellular Longevity. ISSN 1942-0900. 2022, p. 1–15. doi: 10.1155/2022/5019752. Full text in Research Archive Show summary

  The kynurenine pathway is implicated in aging, longevity, and immune regulation, but longitudinal studies and assessment of the cerebrospinal fluid (CSF) are lacking. We investigated tryptophan (Trp) and downstream kynurenine metabolites and their associations with age and change over time in four cohorts using comprehensive, targeted metabolomics. The study included 1574 participants in two cohorts with repeated metabolite measurements (mean age at baseline and ), 3161 community-dwelling older adults (age range 71-74 years), and 109 CSF donors (mean age ). In the first two cohorts, age was associated with kynurenine (Kyn), quinolinic acid (QA), and the kynurenine to tryptophan ratio (KTR), and inversely with Trp. Consistent with these findings, Kyn, QA, and KTR increased over time, whereas Trp decreased. Similarly, QA and KTR were higher in community-dwelling older adults of age 74 compared to 71, whereas Trp was lower. Kyn and QA were more strongly correlated with age in the CSF compared to serum and increased in a subset of participants with repeated CSF sampling () over four years. We assessed associations with frailty and mortality in two cohorts. QA and KTR were most strongly associated with mortality and frailty. Our study provides robust evidence of changes in tryptophan and kynurenine metabolism with human aging and supports links with adverse health outcomes. Our results suggest that aging activates the inflammation and stress-driven kynurenine pathway systemically and in the brain, but we cannot determine whether this activation is harmful or adaptive. We identified a relatively stronger age-related increase of the potentially neurotoxic end-product QA in brain.

• Vidal-Piñeiro, Didac; Sørensen, Øystein; Blennow, Kaj; Capogna, Elettra; Halaas, Nathalie Bodd & Idland, Ane-Victoria [Show all 12 contributors for this article] (2022). Relationship between cerebrospinal fluid neurodegeneration biomarkers and temporal brain atrophy in cognitively healthy older adults. Neurobiology of Aging. ISSN 0197-4580. 116, p. 80–91. doi: 10.1016/j.neurobiolaging.2022.04.010. Full text in Research Archive
• Henjum, Kristi; Watne, Leiv; Godang, Kristin; Halaas, Nathalie Bodd; Eldholm, Rannveig Sakshaug & Blennow, Kaj [Show all 10 contributors for this article] (2022). Cerebrospinal fluid catecholamines in Alzheimer's disease patients with and without biological disease. Translational Psychiatry. ISSN 2158-3188. 12. doi: 10.1038/s41398-022-01901-5. Full text in Research Archive Show summary

  Noradrenergic and dopaminergic neurons are involved in cognitive functions, relate to behavioral and psychological symptoms in dementia and are affected in Alzheimer’s disease (AD). Amyloid plaques (A), neurofibrillary tangles (T) and neurodegeneration (N) hallmarks the AD neuropathology. Today, the AT(N) pathophysiology can be assessed through biomarkers. Previous studies report cerebrospinal fluid (CSF) catecholamine concentrations in AD patients without biomarker refinement. We explored if CSF catecholamines relate to AD clinical presentation or neuropathology as reflected by CSF biomarkers. CSF catecholamines were analyzed in AD patients at the mild cognitive impairment (MCI; n = 54) or dementia stage (n = 240) and in cognitively unimpaired (n = 113). CSF biomarkers determined AT status and indicated synaptic damage (neurogranin). The AD patients (n = 294) had higher CSF noradrenaline and adrenaline concentrations, but lower dopamine concentrations compared to the cognitively unimpaired (n = 113). AD patients in the MCI and dementia stage of the disease had similar CSF catecholamine concentrations. In the CSF neurogranin positively associated with noradrenaline and adrenaline but not with dopamine. Adjusted regression analyses including AT status, CSF neurogranin, age, gender, and APOEε4 status verified the findings. In restricted analyses comparing A+T+ patients to A−T− cognitively unimpaired, the findings for CSF adrenaline remained significant (p < 0.001) but not for CSF noradrenaline (p = 0.07) and CSF dopamine (p = 0.33). There were no differences between A+T+ and A−T− cognitively unimpaired. Thus, we find alterations in CSF catecholamines in symptomatic AD and the CSF adrenergic transmitters to increase simultaneously with synaptic damage as indexed by CSF neurogranin.

• Halaas, Nathalie Bodd; Zetterberg, Henrik; Idland, Ane-Victoria; Knapskog, Anne Brita; Watne, Leiv Otto & Blennow, Kaj (2021). Cerebrospinal Fluid Concentration of Neurogranin in Hip Fracture Patients with Delirium. Journal of Alzheimer's Disease. ISSN 1387-2877. 81(2), p. 1–28. doi: 10.3233/jad-201341.
• Neerland, Bjørn Erik; Halaas, Nathalie Bodd; Idland, Ane-Victoria; Henjum, Kristi; Blennow, Kaj & Zetterberg, Henrik [Show all 7 contributors for this article] (2020). Fatty Acid-Binding Protein 3 in Cerebrospinal Fluid of Hip Fracture Patients with Delirium. Journal of Alzheimer's Disease. ISSN 1387-2877. 77(1), p. 183–190. doi: 10.3233/JAD-200364. Full text in Research Archive
• Edwin, Trine Holt; Henjum, Kristi; Nilsson, Lars; Watne, Leiv; Persson, Karin Ester Torun & Eldholm, Rannveig Sakshaug [Show all 12 contributors for this article] (2020). A high cerebrospinal fluid soluble TREM2 level is associated with slow clinical progression of Alzheimer's disease. Alzheimer's & Dementia. ISSN 1552-5260. 12(1). doi: 10.1002/dad2.12128. Full text in Research Archive Show summary

  Introduction: The progression rate of Alzheimer's disease (AD) varies and might be affected by the triggering receptor expressed on myeloid cells (TREM2) activity. We explored if cerebrospinal fluid (CSF) soluble TREM2 (sTREM2), a proxy of microglial activity, is associated with clinical progression rate. Methods: Patients with clinical AD (N = 231) were followed for up to 3 years after diagnosis. Cognitively healthy controls (N = 42) were followed for 5 years. CSF sTREM2 was analyzed by enzyme-linked immunosorbent assay. Group-based trajectory modeling revealed distinct clinical progression groups. Results: Higher CSF sTREM2 was associated with slow clinical progression. The slow- and medium-progressing groups had higher CSF sTREM2 than the cognitively healthy, who had a similar level to patients with rapid clinical progression. Discussion: CSF sTREM2 levels were associated with clinical progression in AD, regardless of core biomarkers. This could be useful in assessing disease development in relation to patient care and clinical trial recruitment. Keywords: Alzheimer's disease; Clinical Dementia Rating scale; disease progression; soluble triggering receptor expressed on myeloid cells 2 (sTREM2); trajectories.

• Halaas, Nathalie Bodd; Henjum, Kristi; Blennow, Kaj; Dakhil, Shams; Idland, Ane-Victoria & Nilsson, Lars [Show all 13 contributors for this article] (2019). CSF sTREM2 and Tau Work Together in Predicting Increased Temporal Lobe Atrophy in Older Adults. Cerebral Cortex. ISSN 1047-3211. 00, p. 1–12. doi: 10.1093/cercor/bhz240. Full text in Research Archive
• Halaas, Nathalie Bodd; Blennow, Kaj; Idland, Ane-Victoria; Wyller, Torgeir Bruun; Ræder, Johan & Frihagen, Frede Jon [Show all 9 contributors for this article] (2018). Neurofilament light in serum and cerebrospinal fluid of hip fracture patients with delirium. Dementia and Geriatric Cognitive Disorders. ISSN 1420-8008. 46(5-6), p. 346–357. doi: 10.1159/000494754. Full text in Research Archive

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• Hella, Mathias Nikolai Petersen; Bergland, Anne Katrine; Soennesyn, Hogne; Halaas, Nathalie Bodd; Watne, Leiv & Bonanni, Laura [Show all 7 contributors for this article] (2023). What we know about the possible link between delirium and dementia with Lewy bodies, and why we need to learn more. Acta Psychiatrica Scandinavica. ISSN 0001-690X. 147(5), p. 401–402. doi: 10.1111/acps.13526.

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