Lars Nilsson

• Pagnon de la Vega, María; Syvänen, Stina; Giedraitis, Vilmantas; Hooley, Monique; Konstantinidis, Evangelos & Meier, Silvio R. [Show all 16 contributors for this article] (2024). Altered amyloid-β structure markedly reduces gliosis in the brain of mice harboring the Uppsala APP deletion. Acta neuropathologica communications. ISSN 2051-5960. 12(1). doi: 10.1186/s40478-024-01734-x.
• Zielinski, Mara; Peralta Reyes, Fernanda S.; Gremer, Lothar; Schemmert, Sarah; Frieg, Benedikt & Schäfer, Luisa U. [Show all 15 contributors for this article] (2023). Cryo-EM of Aβ fibrils from mouse models find tg-APP<inf>ArcSwe</inf> fibrils resemble those found in patients with sporadic Alzheimer’s disease. Nature Neuroscience. ISSN 1097-6256. 26, p. 2073–2080. doi: 10.1038/s41593-023-01484-4. Full text in Research Archive
• Sulheim, Einar; Widerøe, Marius; Bäck, Marcus; Nilsson, K Peter R; Hammarström, Per & Nilsson, Lars [Show all 8 contributors for this article] (2023). Contrast Enhanced Magnetic Resonance Imaging of Amyloid-β Plaques in a Murine Alzheimer's Disease Model. Journal of Alzheimer's Disease. ISSN 1387-2877. 93(2), p. 411–419. doi: 10.3233/JAD-220198. Full text in Research Archive
• Åbjørsbråten, Knut Sindre; Skaaraas, Gry Helen Enger Syverstad; Cunen, Celine Marie Løken; Bjørnstad, Daniel Marelius; Binder, Kristin Maria Gullestad & Bojarskaite, Laura [Show all 15 contributors for this article] (2022). Impaired astrocytic Ca2+ signaling in awake-behaving Alzheimer’s disease transgenic mice. eLIFE. ISSN 2050-084X. doi: 10.7554/eLife.75055. Full text in Research Archive Show summary

  Increased astrocytic Ca2+ signaling has been shown in Alzheimer’s disease mouse models, but to date no reports have characterized behaviorally induced astrocytic Ca2+ signaling in such mice. Here, we employ an event-based algorithm to assess astrocytic Ca2+ signals in the neocortex of awake-behaving tg-ArcSwe mice and non-transgenic wildtype littermates while monitoring pupil responses and behavior. We demonstrate an attenuated astrocytic Ca2+ response to locomotion and an uncoupling of pupil responses and astrocytic Ca2+ signaling in 15-month-old plaque-bearing mice. Using the genetically encoded fluorescent norepinephrine sensor GRABNE, we demonstrate a reduced norepinephrine signaling during spontaneous running and startle responses in the transgenic mice, providing a possible mechanistic underpinning of the observed reduced astrocytic Ca2+ responses. Our data points to a dysfunction in the norepinephrine–astrocyte Ca2+ activity axis, which may account for some of the cognitive deficits observed in Alzheimer’s disease.

• De la Vega, María Pagnon; Giedraitis, Vilmantas; Michno, Wojciech; Kilander, Lena; Güner, Gökhan & Zielinski, Mara [Show all 21 contributors for this article] (2021). The Uppsala APP deletion causes early onset autosomal dominant Alzheimer's disease by altering APP processing and increasing amyloid β fibril formation. Science Translational Medicine. ISSN 1946-6234. 13:eabc6184(606), p. 1–13. doi: 10.1126/scitranslmed.abc6184. 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.

• Knapskog, Anne Brita; Henjum, Kristi; Idland, Ane-Victoria; Eldholm, Rannveig Sakshaug; Persson, Karin Ester Torun & Saltvedt, Ingvild [Show all 9 contributors for this article] (2020). Cerebrospinal fluid sTREM2 in Alzheimer’s disease: comparisons between clinical presentation and AT classification. Scientific Reports. ISSN 2045-2322. 10, p. 1–10. doi: 10.1038/s41598-020-72878-8. Full text in Research Archive Show summary

  Triggering receptor expressed on myeloid cells 2 (TREM2) is an innate immune receptor expressed by microglia. Its cleaved fragments, soluble TREM2 (sTREM2), can be measured in the cerebrospinal fluid (CSF). Previous studies indicate higher CSF sTREM2 in symptomatic AD; however most of these studies have included biomarker positive AD cases and biomarker negative controls. The aim of the study was to explore potential differences in the CSF level of sTREM2 and factors associated with an increased sTREM2 level in patients diagnosed with mild cognitive impairment (MCI) or dementia due to AD compared with cognitively unimpaired controls as judged by clinical symptoms and biomarker category (AT). We included 299 memory clinic patients, 62 (20.7%) with AD-MCI and 237 (79.3%) with AD dementia, and 113 cognitively unimpaired controls. CSF measures of the core biomarkers were applied to determine AT status. CSF sTREM2 was analyzed by ELISA. Patients presented with comparable CSF sTREM2 levels as the cognitively unimpaired (9.6 ng/ml [SD 4.7] versus 8.8 ng/ml [SD 3.6], p = 0.27). We found that CSF sTREM2 associated with age-related neuroinflammation and tauopathy irrespectively of amyloid β, APOE ε4 status or gender. The findings were similar in both symptomatic and non-symptomatic individuals.

• Henjum, Kristi; Årskog, Vibeke Helen; Jendresen, Charlotte Bille; Fladby, Tormod; Torp, Reidun & Nilsson, Lars (2020). Analyzing microglial-associated Aβ in Alzheimer’s disease transgenic mice with a novel mid-domain Aβ-antibody. Scientific Reports. ISSN 2045-2322. 10(10590). doi: 10.1038/s41598-020-67419-2. Full text in Research Archive
• 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
• Jendresen, Charlotte Bille; Digre, Andreas; Cui, Hao; Zhang, Xiao; Vlodavsky, Israel & Li, Jin-Ping [Show all 7 contributors for this article] (2019). Systemic LPS-induced Aβ-solubilization and clearance in AβPP-transgenic mice is diminished by heparanase overexpression. Scientific Reports. ISSN 2045-2322. 9:4600(1), p. 1–12. doi: 10.1038/s41598-019-40999-4. Full text in Research Archive

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