Faglige interesser
- Alzheimers sykdom
- Amyloidose
- CNS-farmakologi
- Neurodegeneration
Undervisning
- Farmakologi-undervisning for medisinstudenter
Bakgrunn
- Apotekarexamen, Uppsala Universitet, 1988
- PhD Neurobiologi, Karolinska Institutet, 1996
- Postdoctoral fellow, Hardvard Medical School og University South Florida, USA, 1998-2002
- Senior Forskare, Uppsala Universitet, Sverige, 2003-2011
- Professor I Farmakologi, Universitetet i Oslo, 2012-
Emneord:
Hjerne og nervesystem,
Nevrodegenerative sykdommer
Publikasjoner
Utvalgte publikasjoner
- Jendresen C, Årskog V, Daws MR, Nilsson LNG (2017) The Alzheimer's disease risk factors apolipoprotein E and TREM2 are linked in a receptor signaling pathway. J Neuroinflammation 14(1):59.
- Henjum K, Almdahl IS, Årskog V, Minthon L, Hansson O, Fladby T, Nilsson LNG (2016) Cerebrospinal fluid soluble TREM2 in aging and Alzheimer's disease. Alzheimers Res Ther. 27;8(1):17.
- Rogeberg M., Almdahl IS., Wettergren M., Nilsson LNG., Fladby T (2015) Isobaric Quantification of Cerebrospinal Fluid Amyloid-β Peptides in Alzheimer's Disease: C-Terminal Truncation Relates to Early Measures of Neurodegeneration. J Proteome Res 14, 4834-43.
- Rogeberg M, Wettergreen M, Nilsson LNG, Fladby T (2015) Identification of amyloid-β mid-domain fragments in human cerebrospinal fluid. Biochimie, 113:86-92.
- Jendresen CB, Cui H, Zhang X, Vlodavsky I, Nilsson LNG, Li JP, (2015) Overexpression of heparanase lowers amyloid burden in AβPP transgenic mice. J Biol. Chem. 290:5053-64.
- Nuruddin S., Syverstad GH., Lillehaug S., Leergaard TB., Nilsson LNG., Ropstad E., Krogenæsa A., Haraldsen I., Torp R. (2014) Elevated mRNA-levels of gonadotropin-releasing hormone and its receptor in plaque-bearing Alzheimer´s disease transgenic mice. Plos One 9(8):e103607.
- Lillehaug SD., Syverstad GH., Nilsson LNG., Bjaalie JG., Leergaard TB., Torp R. (2014) Brain-wide distribution and variance of amyloid-beta load in middle aged -transgenic Alzheimer’s disease mice with both the Artic and Swedish AβPP mutations. Neurobiol Aging 35(3):556-64.
- Gumucio A., Lannfelt L., Nilsson LNG (2013) Lack of exon 10 in the murine tau gene results in mild sensorimotor defects with aging. BMC Neurosci. 14:148.
- Lillenes MS., Støen M., Torp R., Nilsson LNG., Günter C-C., Tonjum T. (2013) Transient changes in expression of OGG1, APE1 and PolB in the brains of mice expressing mutant amyloid-β precursor protein (AβPP). Mech. Ageing Dev 134(10):467-77.
- Philipson O, Lord A, Lalowski M, Soliyman R, Thyberg R, Baumann M, Thyberg J, Bogdanovic N, Olofsson T, Tjernberg L, Ingelsson I, Lannfelt L, Kalimo H and Nilsson LNG (2011) The Arctic mutation results in distinct plaques and accumulation of N- and C-truncated Aβ. Neurobiology of Aging, PMID: 22118948.
- Yang J., Olson L., Nuntagij P., Oguchi T., Camassa LMA, Nilsson LNG, Lannfelt L., Xu Y., Amiry-Moghaddam M., Ottersen OP., Torp R. (2011) Loss of astrocyte polarization in the tg-ArcSwe mouse model of Alzheimer’s disease. Journal Alzheimer’s disease 27(4):711-22.
- Lord A, Philipson P, Klingstedt T, Westermark G, Hammarström P, Nilsson KP and Nilsson LNG (2011) Observations in APP bitransgenic mice suggest that diffuse and compact plaques form by independent processes in Alzheimer’s disease. American Journal of Pathology, 178(5): 2286-2298.
- Codita, A, Gumucio A, Lannfelt L, Gellerfors P, Winblad B, Mohammed A.K, Nilsson LNG (2010) Impaired behavior of female tg-ArcSwe APP mice in the IntelliCage: a longitudinal study. Behav. Brain Research, 215:83-94.
- Philipson O., Lannfelt L. and Nilsson LNG (2009) Genetic and pharmacological evidence of intraneuronal Aβ accumulation in APP transgenic mice. FEBS Lett., 583: 3021-6.
- Lord A., Gumucio-Gatica A., Englund H., Sehlin D., Sundquist V., Söderberg L., Möller C., Gellerfors P., Lannfelt L., Ekholm Pettersson F. and Nilsson LNG (2009) An amyloid-β protofibril-selective antibody prevents amyloid formation in a mouse model of Alzheimer’s disease. Neurobiol. Dis., 36: 425-34.
- Lord A., Englund H., Söderberg L., Tucker S., Clausen F., Hillered L., Gordon MN., Morgan D., Lannfelt L., Ekholm-Pettersson F., Nilsson LNG (2009) Amyloid-β protofibrils correlate with spatial learning in Arctic Alzheimer’s disease transgenic mice. FEBS.J., 276, 995-1006.
- Philipsson O., Hammarström P., Nilsson PKR., Portelius E., Blennow K., Olofsson T., Ingelson M., Hyman BT., Blennow K., Lannfelt L., Kalimo H., Nilsson LNG (2009) A highly insoluble state of Aβ is found in both Alzheimer´s disease brain and in transgenic mice with the Arctic mutation. Neurobiol. Aging 30:1393-1405.
- Lord A., Kalimo H., Eckman C., Zhang X-Q., Lannfelt L. and Nilsson LNG (2006) The Arctic Alzheimer mutation facilitates early intraneuronal Aβ aggregation and senile plaque formation in transgenic mice. Neurobiol. Aging, 27: 67-77.
- Stenh C., Englund H., Lord A., Johansson A-S., Almeida CG, Gellerfors P., Greengard P., Gouras GK., Lannfelt L., Nilsson LNG (2005) Oligomers of amyloid- are inefficiently measured by ELISA. Ann Neurol., 58: 147-150.
- Nilsson LNG, Arendash GW., Low MA., Leighty RE., Costa DA., Rojiani A., Wu X., Bales KR., Paul SM. and Potter H. (2004) Cognitive impairment in PDAPP mice depends on Apolipoprotein E and ACT-catalyzed amyloid formation. Neurobiol. Aging, 25(9): 1153-67.
- Nilsson LNG, Bales KR., DiCarlo G., Gordon MN., Morgan D., Paul SM. and Potter H. (2001) Alpha-1-antichymotrypsin promotes -sheet amyloid plaque deposition in a transgenic mouse model of Alzheimer’s disease. J. Neurosci., 21(5): 1444-1451.
- Rogers J., Leiter L., McPhee J., Zhan SS., Potter H. and Nilsson LNG (1999) Translation of the Alzheimer’s amyloid precursor protein mRNA is up-regulated by interleukin-1 through 5’ untranslated region sequences. J. Biol. Chem., 274(10): 6421-6431.
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Åbjørsbråten, Knut Sindre; Skaaraas, Gry Helen Enger Syverstad; Cunen, Celine Marie Løken; Bjørnstad, Daniel Marelius; Binder, Kristin Maria Gullestad & Bojarskaite, Laura
[Vis alle 15 forfattere av denne artikkelen]
(2022).
Impaired astrocytic Ca2+ signaling in awake-behaving Alzheimer’s disease transgenic mice.
eLIFE.
ISSN 2050-084X.
doi:
10.7554/eLife.75055.
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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.
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Edwin, Trine Holt; Henjum, Kristi; Nilsson, Lars; Watne, Leiv; Persson, Karin Ester Torun & Eldholm, Rannveig Sakshaug
[Vis alle 12 forfattere av denne artikkelen]
(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.
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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.
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Knapskog, Anne Brita; Henjum, Kristi; Idland, Ane-Victoria; Eldholm, Rannveig Sakshaug; Persson, Karin Ester Torun & Saltvedt, Ingvild
[Vis alle 9 forfattere av denne artikkelen]
(2020).
Cerebrospinal fluid sTREM2 in Alzheimer’s disease: comparisons between clinical presentation and AT classification.
Scientific Reports.
ISSN 2045-2322.
10,
s. 1–10.
doi:
10.1038/s41598-020-72878-8.
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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.
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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.
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Jendresen, Charlotte Bille; Daws, Michael Rory & Nilsson, Lars
(2018).
An improved CPRG colorimetric ligand-receptor signal transduction assay based on beta-galactosidase activity in mammalian BWZ-reporter cells.
Journal of pharmacological and toxicological methods.
ISSN 1056-8719.
90,
s. 67–75.
doi:
10.1016/j.vascn.2017.11.004.
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Jendresen, Charlotte Bille; Årskog, Vibeke Helen; Daws, Michael Rory & Nilsson, Lars
(2017).
The Alzheimer's disease risk factors apolipoprotein E and TREM2 are linked in a receptor signaling pathway.
Journal of Neuroinflammation.
ISSN 1742-2094.
14:59,
s. 1–13.
doi:
10.1186/s12974-017-0835-4.
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Røgeberg, Magnus; Almdahl, Ina; Wettergreen, Marianne; Nilsson, Lars & Fladby, Tormod
(2015).
Isobaric Quantification of Cerebrospinal Fluid Amyloid-β Peptides in Alzheimer's Disease: C-Terminal Truncation Relates to Early Measures of Neurodegeneration.
Journal of Proteome Research.
ISSN 1535-3893.
14(11),
s. 4834–4843.
doi:
10.1021/acs.jproteome.5b00668.
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Røgeberg, Magnus; Wettergreen, Marianne; Nilsson, Lars & Fladby, Tormod
(2015).
Identification of amyloid beta mid-domain fragments in human cerebrospinal fluid.
Biochimie.
ISSN 0300-9084.
113,
s. 86–92.
doi:
10.1016/j.biochi.2015.03.022.
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Jendresen, Charlotte Bille; Cui, Hao; Zhang, Xiao; Vlodavsky, Israel; Nilsson, Lars & Li, Jin-Ping
(2015).
Overexpression of heparanase lowers the amyloid burden in amyloid-β precursor Protein Transgenic mice.
Journal of Biological Chemistry.
ISSN 0021-9258.
290(8),
s. 5053–5064.
doi:
10.1074/jbc.M114.600569.
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Nuruddin, Syed; Syverstad, Gry-Helen Enger; Lillehaug, Sveinung; Leergaard, Trygve Brauns; Nilsson, Lars & Ropstad, Erik
[Vis alle 9 forfattere av denne artikkelen]
(2014).
Elevated mRNA-Levels of Gonadotropin-Releasing Hormone and Its Receptor in Plaque-Bearing Alzheimer's Disease Transgenic Mice.
PLOS ONE.
ISSN 1932-6203.
9(8).
doi:
10.1371/journal.pone.0103607.
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Lillehaug, Sveinung; Syverstad, Gry-Helen Enger; Nilsson, Lars; Bjaalie, Jan G.; Leergaard, Trygve Brauns & Torp, Reidun
(2014).
Brainwide distribution and variance of amyloid-beta deposits in tg-ArcSwe mice.
Neurobiology of Aging.
ISSN 0197-4580.
35(3),
s. 556–564.
doi:
10.1016/j.neurobiolaging.2013.09.013.
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Gumucio, Astrid; Lannfelt, Lars & Nilsson, Lars
(2013).
Lack of exon 10 in the murine tau gene results in mild sensorimotor defects with aging.
BMC Neuroscience.
ISSN 1471-2202.
14:148.
doi:
10.1186/1471-2202-14-148.
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Lillenes, Meryl Sønderby; Støen, Mari; Gómez-Muñoz, Marta; Torp, Reidun; Günther, Clara-Cecilie & Nilsson, Lars
[Vis alle 7 forfattere av denne artikkelen]
(2013).
Transient OGG1, APE1, PARP1 and Polβ expression in an Alzheimer's disease mouse model.
Mechanisms of Ageing and Development.
ISSN 0047-6374.
134(10),
s. 467–477.
doi:
10.1016/j.mad.2013.09.002.
Vis sammendrag
Alzheimer's disease (AD) is a disease of major public health significance, whose pathogenesis is strongly linked to the presence of fibrillar aggregates of amyloid-beta (Aβ) in the aging human brain. We exploited the transgenic (Tg)-ArcSwe mouse model for human AD to explore whether oxidative stress and the capacity to repair oxidative DNA damage via base excision repair (BER) are related to Aβ pathology in AD. Tg-ArcSwe mice express variants of Aβ, accumulating senile plaques at 4–6 months of age, and develop AD-like neuropathology as adult animals. The relative mRNA levels of genes encoding BER enzymes, including 8-oxoguanine glycosylase (OGG1), AP endonuclease 1 (APE1), polymerase β (Polβ) and poly(ADP-ribose) polymerase 1 (PARP1), were quantified in various brain regions of 6 weeks, 4 months and 12 months old mice. The results show that OGG1 transcriptional expression was higher, and APE1 expression lower, in 4 months old Tg-ArcSwe than in wildtype (wt) mice. Furthermore, Polβ transcriptional expression was significantly lower in transgenic 12 months old mice than in wt. Transcriptional profiling also showed that BER repair capacity vary during the lifespan in Tg-ArcSwe and wt mice. The BER expression pattern in Tg-ArcSwe mice thus reflects responses to oxidative stress in vulnerable brain structures.
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Se alle arbeider i Cristin
Publisert
26. jan. 2012 10:00
- Sist endret
31. mai 2022 15:15