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CSF progranulin increases in the course of Alzheimer's disease and is associated with sTREM2, neurodegeneration and cognitive decline.

Suárez-Calvet M, Capell A, Araque Caballero MÁ, Morenas-Rodríguez E, Fellerer K, Franzmeier N, Kleinberger G, Eren E, Deming Y, Piccio L, Karch CM, Cruchaga C, Paumier K, Bateman RJ, Fagan AM, Morris JC, Levin J, Danek A, Jucker M, Masters CL, Rossor MN, Ringman JM, Shaw LM, Trojanowski JQ, Weiner M, Ewers M, Haass C; Dominantly Inherited Alzheimer Network; Alzheimer's Disease Neuroimaging Initiative.

EMBO Mol Med. 2018 Nov 27. pii: e9712. doi: 10.15252/emmm.201809712. [Epub ahead of print]


Early and longitudinal microglial activation but not amyloid accumulation predict cognitive outcome in PS2APP mice.

Focke C, Blume T, Zott B, Shi Y, Deussing M, Peters F, Schmidt C, Kleinberger G, Lindner S, Gildehaus FJ, Beyer L, von Ungern-Sternberg B, Bartenstein P, Ozmen L, Baumann K, Dorostkar MM, Haass C, Adelsberger H, Herms J, Rominger A, Brendel M.

J Nucl Med. 2018 Sep 27. pii: jnumed.118.217703. doi: 10.2967/jnumed.118.217703. [Epub ahead of print]


The Trem2 R47H Alzheimer's risk variant impairs splicing and reduces Trem2 mRNA and protein in mice but not in humans.

Xiang X, Piers TM, Wefers B, Zhu K, Mallach A, Brunner B, Kleinberger G, Song W, Colonna M, Herms J, Wurst W, Pocock JM, Haass C.

Mol Neurodegener. 2018 Sep 6;13(1):49. doi: 10.1186/s13024-018-0280-6.


An Alzheimer-associated TREM2 variant occurs at the ADAM cleavage site and affects shedding and phagocytic function.

Schlepckow K, Kleinberger G, Fukumori A, Feederle R, Lichtenthaler SF, Steiner H, Haass C.

EMBO Mol Med. 2017 Oct;9(10):1356-1365. doi: 10.15252/emmm.201707672.


Time Courses of Cortical Glucose Metabolism and Microglial Activity Across the Life Span of Wild-Type Mice: A PET Study.

Brendel M, Focke C, Blume T, Peters F, Deussing M, Probst F, Jaworska A, Overhoff F, Albert N, Lindner S, von Ungern-Sternberg B, Bartenstein P, Haass C, Kleinberger G, Herms J, Rominger A.

J Nucl Med. 2017 Dec;58(12):1984-1990. doi: 10.2967/jnumed.117.195107. Epub 2017 Jul 13.


The FTD-like syndrome causing TREM2 T66M mutation impairs microglia function, brain perfusion, and glucose metabolism.

Kleinberger G, Brendel M, Mracsko E, Wefers B, Groeneweg L, Xiang X, Focke C, Deußing M, Suárez-Calvet M, Mazaheri F, Parhizkar S, Pettkus N, Wurst W, Feederle R, Bartenstein P, Mueggler T, Arzberger T, Knuesel I, Rominger A, Haass C.

EMBO J. 2017 Jul 3;36(13):1837-1853. doi: 10.15252/embj.201796516. Epub 2017 May 30.


TREM2 deficiency impairs chemotaxis and microglial responses to neuronal injury.

Mazaheri F, Snaidero N, Kleinberger G, Madore C, Daria A, Werner G, Krasemann S, Capell A, Trümbach D, Wurst W, Brunner B, Bultmann S, Tahirovic S, Kerschensteiner M, Misgeld T, Butovsky O, Haass C.

EMBO Rep. 2017 Jul;18(7):1186-1198. doi: 10.15252/embr.201743922. Epub 2017 May 8.


Increase of TREM2 during Aging of an Alzheimer's Disease Mouse Model Is Paralleled by Microglial Activation and Amyloidosis.

Brendel M, Kleinberger G, Probst F, Jaworska A, Overhoff F, Blume T, Albert NL, Carlsen J, Lindner S, Gildehaus FJ, Ozmen L, Suárez-Calvet M, Bartenstein P, Baumann K, Ewers M, Herms J, Haass C, Rominger A.

Front Aging Neurosci. 2017 Jan 31;9:8. doi: 10.3389/fnagi.2017.00008. eCollection 2017.


The APOE ε4 genotype modulates CSF YKL-40 levels and their structural brain correlates in the continuum of Alzheimer's disease but not those of sTREM2.

Gispert JD, Monté GC, Suárez-Calvet M, Falcon C, Tucholka A, Rojas S, Rami L, Sánchez-Valle R, Lladó A, Kleinberger G, Haass C, Molinuevo JL.

Alzheimers Dement (Amst). 2016 Dec 22;6:50-59. doi: 10.1016/j.dadm.2016.12.002. eCollection 2017.


Early changes in CSF sTREM2 in dominantly inherited Alzheimer's disease occur after amyloid deposition and neuronal injury.

Suárez-Calvet M, Araque Caballero MÁ, Kleinberger G, Bateman RJ, Fagan AM, Morris JC, Levin J, Danek A, Ewers M, Haass C; Dominantly Inherited Alzheimer Network.

Sci Transl Med. 2016 Dec 14;8(369):369ra178.


Cerebrospinal fluid sTREM2 levels are associated with gray matter volume increases and reduced diffusivity in early Alzheimer's disease.

Gispert JD, Suárez-Calvet M, Monté GC, Tucholka A, Falcon C, Rojas S, Rami L, Sánchez-Valle R, Lladó A, Kleinberger G, Haass C, Molinuevo JL.

Alzheimers Dement. 2016 Dec;12(12):1259-1272. doi: 10.1016/j.jalz.2016.06.005. Epub 2016 Jul 14.


TREM2 deficiency reduces the efficacy of immunotherapeutic amyloid clearance.

Xiang X, Werner G, Bohrmann B, Liesz A, Mazaheri F, Capell A, Feederle R, Knuesel I, Kleinberger G, Haass C.

EMBO Mol Med. 2016 Sep 1;8(9):992-1004. doi: 10.15252/emmm.201606370. Print 2016 Sep.


sTREM2 cerebrospinal fluid levels are a potential biomarker for microglia activity in early-stage Alzheimer's disease and associate with neuronal injury markers.

Suárez-Calvet M, Kleinberger G, Araque Caballero MÁ, Brendel M, Rominger A, Alcolea D, Fortea J, Lleó A, Blesa R, Gispert JD, Sánchez-Valle R, Antonell A, Rami L, Molinuevo JL, Brosseron F, Traschütz A, Heneka MT, Struyfs H, Engelborghs S, Sleegers K, Van Broeckhoven C, Zetterberg H, Nellgård B, Blennow K, Crispin A, Ewers M, Haass C.

EMBO Mol Med. 2016 May 2;8(5):466-76. doi: 10.15252/emmm.201506123. Print 2016 May.


Glial Activation and Glucose Metabolism in a Transgenic Amyloid Mouse Model: A Triple-Tracer PET Study.

Brendel M, Probst F, Jaworska A, Overhoff F, Korzhova V, Albert NL, Beck R, Lindner S, Gildehaus FJ, Baumann K, Bartenstein P, Kleinberger G, Haass C, Herms J, Rominger A.

J Nucl Med. 2016 Jun;57(6):954-60. doi: 10.2967/jnumed.115.167858. Epub 2016 Feb 18.


Reduced secretion and altered proteolytic processing caused by missense mutations in progranulin.

Kleinberger G, Capell A, Brouwers N, Fellerer K, Sleegers K, Cruts M, Van Broeckhoven C, Haass C.

Neurobiol Aging. 2016 Mar;39:220.e17-26. doi: 10.1016/j.neurobiolaging.2015.12.014. Epub 2015 Dec 29.


Investigating the role of filamin C in Belgian patients with frontotemporal dementia linked to GRN deficiency in FTLD-TDP brains.

Janssens J, Philtjens S, Kleinberger G, Van Mossevelde S, van der Zee J, Cacace R, Engelborghs S, Sieben A, Banzhaf-Strathmann J, Dillen L, Merlin C, Cuijt I, Robberecht C, Schmid B, Santens P, Ivanoiu A, Vandenbulcke M, Vandenberghe R, Cras P, De Deyn PP, Martin JJ, Maudsley S, Haass C, Cruts M, Van Broeckhoven C; Belgian Neurology (BELNEU) consortium.

Acta Neuropathol Commun. 2015 Nov 10;3:68. doi: 10.1186/s40478-015-0246-7.


Functional complementation in Drosophila to predict the pathogenicity of TARDBP variants: evidence for a loss-of-function mechanism.

Vanden Broeck L, Kleinberger G, Chapuis J, Gistelinck M, Amouyel P, Van Broeckhoven C, Lambert JC, Callaerts P, Dermaut B.

Neurobiol Aging. 2015 Feb;36(2):1121-9. doi: 10.1016/j.neurobiolaging.2014.09.001. Epub 2014 Sep 28.


TREM2 mutations implicated in neurodegeneration impair cell surface transport and phagocytosis.

Kleinberger G, Yamanishi Y, Suárez-Calvet M, Czirr E, Lohmann E, Cuyvers E, Struyfs H, Pettkus N, Wenninger-Weinzierl A, Mazaheri F, Tahirovic S, Lleó A, Alcolea D, Fortea J, Willem M, Lammich S, Molinuevo JL, Sánchez-Valle R, Antonell A, Ramirez A, Heneka MT, Sleegers K, van der Zee J, Martin JJ, Engelborghs S, Demirtas-Tatlidede A, Zetterberg H, Van Broeckhoven C, Gurvit H, Wyss-Coray T, Hardy J, Colonna M, Haass C.

Sci Transl Med. 2014 Jul 2;6(243):243ra86. doi: 10.1126/scitranslmed.3009093.


Common pathobiochemical hallmarks of progranulin-associated frontotemporal lobar degeneration and neuronal ceroid lipofuscinosis.

Götzl JK, Mori K, Damme M, Fellerer K, Tahirovic S, Kleinberger G, Janssens J, van der Zee J, Lang CM, Kremmer E, Martin JJ, Engelborghs S, Kretzschmar HA, Arzberger T, Van Broeckhoven C, Haass C, Capell A.

Acta Neuropathol. 2014;127(6):845-60. doi: 10.1007/s00401-014-1262-6. Epub 2014 Mar 12.


Overexpression of ALS-associated p.M337V human TDP-43 in mice worsens disease features compared to wild-type human TDP-43 mice.

Janssens J, Wils H, Kleinberger G, Joris G, Cuijt I, Ceuterick-de Groote C, Van Broeckhoven C, Kumar-Singh S.

Mol Neurobiol. 2013 Aug;48(1):22-35. doi: 10.1007/s12035-013-8427-5. Epub 2013 Mar 10.


hnRNP A3 binds to GGGGCC repeats and is a constituent of p62-positive/TDP43-negative inclusions in the hippocampus of patients with C9orf72 mutations.

Mori K, Lammich S, Mackenzie IR, Forné I, Zilow S, Kretzschmar H, Edbauer D, Janssens J, Kleinberger G, Cruts M, Herms J, Neumann M, Van Broeckhoven C, Arzberger T, Haass C.

Acta Neuropathol. 2013 Mar;125(3):413-23. doi: 10.1007/s00401-013-1088-7. Epub 2013 Feb 5.


TDP-43 loss-of-function causes neuronal loss due to defective steroid receptor-mediated gene program switching in Drosophila.

Vanden Broeck L, Naval-Sánchez M, Adachi Y, Diaper D, Dourlen P, Chapuis J, Kleinberger G, Gistelinck M, Van Broeckhoven C, Lambert JC, Hirth F, Aerts S, Callaerts P, Dermaut B.

Cell Rep. 2013 Jan 31;3(1):160-72. doi: 10.1016/j.celrep.2012.12.014. Epub 2013 Jan 17.


Mechanisms of granulin deficiency: lessons from cellular and animal models.

Kleinberger G, Capell A, Haass C, Van Broeckhoven C.

Mol Neurobiol. 2013 Feb;47(1):337-60. doi: 10.1007/s12035-012-8380-8. Epub 2012 Dec 13. Review.


Cellular ageing, increased mortality and FTLD-TDP-associated neuropathology in progranulin knockout mice.

Wils H, Kleinberger G, Pereson S, Janssens J, Capell A, Van Dam D, Cuijt I, Joris G, De Deyn PP, Haass C, Van Broeckhoven C, Kumar-Singh S.

J Pathol. 2012 Sep;228(1):67-76. doi: 10.1002/path.4043. Epub 2012 Jun 25.


A C9orf72 promoter repeat expansion in a Flanders-Belgian cohort with disorders of the frontotemporal lobar degeneration-amyotrophic lateral sclerosis spectrum: a gene identification study.

Gijselinck I, Van Langenhove T, van der Zee J, Sleegers K, Philtjens S, Kleinberger G, Janssens J, Bettens K, Van Cauwenberghe C, Pereson S, Engelborghs S, Sieben A, De Jonghe P, Vandenberghe R, Santens P, De Bleecker J, Maes G, Bäumer V, Dillen L, Joris G, Cuijt I, Corsmit E, Elinck E, Van Dongen J, Vermeulen S, Van den Broeck M, Vaerenberg C, Mattheijssens M, Peeters K, Robberecht W, Cras P, Martin JJ, De Deyn PP, Cruts M, Van Broeckhoven C.

Lancet Neurol. 2012 Jan;11(1):54-65. doi: 10.1016/S1474-4422(11)70261-7. Epub 2011 Dec 7. Erratum in: Lancet Neurol. 2012 Feb;11(2):125.


The role of mutant TAR DNA-binding protein 43 in amyotrophic lateral sclerosis and frontotemporal lobar degeneration.

Janssens J, Kleinberger G, Wils H, Van Broeckhoven C.

Biochem Soc Trans. 2011 Aug;39(4):954-9. doi: 10.1042/BST0390954. Review.


TMEM106B is associated with frontotemporal lobar degeneration in a clinically diagnosed patient cohort.

van der Zee J, Van Langenhove T, Kleinberger G, Sleegers K, Engelborghs S, Vandenberghe R, Santens P, Van den Broeck M, Joris G, Brys J, Mattheijssens M, Peeters K, Cras P, De Deyn PP, Cruts M, Van Broeckhoven C.

Brain. 2011 Mar;134(Pt 3):808-15. doi: 10.1093/brain/awr007.


Increased caspase activation and decreased TDP-43 solubility in progranulin knockout cortical cultures.

Kleinberger G, Wils H, Ponsaerts P, Joris G, Timmermans JP, Van Broeckhoven C, Kumar-Singh S.

J Neurochem. 2010 Nov;115(3):735-47. doi: 10.1111/j.1471-4159.2010.06961.x. Epub 2010 Sep 24.


TDP-43 transgenic mice develop spastic paralysis and neuronal inclusions characteristic of ALS and frontotemporal lobar degeneration.

Wils H, Kleinberger G, Janssens J, Pereson S, Joris G, Cuijt I, Smits V, Ceuterick-de Groote C, Van Broeckhoven C, Kumar-Singh S.

Proc Natl Acad Sci U S A. 2010 Feb 23;107(8):3858-63. doi: 10.1073/pnas.0912417107. Epub 2010 Feb 3.


Progranulin expression correlates with dense-core amyloid plaque burden in Alzheimer disease mouse models.

Pereson S, Wils H, Kleinberger G, McGowan E, Vandewoestyne M, Van Broeck B, Joris G, Cuijt I, Deforce D, Hutton M, Van Broeckhoven C, Kumar-Singh S.

J Pathol. 2009 Oct;219(2):173-81. doi: 10.1002/path.2580.


Influence of a novel amino acid solution (enriched with the dipeptide glycyl-tyrosine) on plasma amino acid concentration of patients with acute renal failure.

Smolle KH, Kaufmann P, Fleck S, Lueger A, Mausser G, Pölz W, Kleinberger G, Krejs GJ.

Clin Nutr. 1997 Oct;16(5):239-46.


Amino acid kinetics in patients with sepsis.

Druml W, Heinzel G, Kleinberger G.

Am J Clin Nutr. 2001 May;73(5):908-13.


Hypophosphatemia in patients with chronic renal failure during total parenteral nutrition.

Druml W, Kleinberger G.

JPEN J Parenter Enteral Nutr. 1999 Jan-Feb;23(1):45-6. No abstract available.


Energy metabolism in patients with acute and chronic liver disease.

Schneeweiss B, Graninger W, Ferenci P, Eichinger S, Grimm G, Schneider B, Laggner AN, Lenz K, Kleinberger G.

Hepatology. 1990 Mar;11(3):387-93.


Assessment of oxygen-consumption by use of reverse Fick-principle and indirect calorimetry in critically ill patients.

Schneeweiss B, Druml W, Graninger W, Grimm G, Kleinberger G, Lenz K, Laggner A.

Clin Nutr. 1989 Apr;8(2):89-93.


Beneficial effect of 8-ornithin vasopressin on renal dysfunction in decompensated cirrhosis.

Lenz K, Hörtnagl H, Druml W, Grimm G, Laggner A, Schneeweisz B, Kleinberger G.

Gut. 1989 Jan;30(1):90-6.


Influence of fluid replacement on extravascular lung water (EVLW) in patients with diabetic ketoacidosis.

Laggner AN, Lenz K, Kleinberger G, Sommer G, Druml W, Schneeweiss B.

Intensive Care Med. 1988;14(3):201-5.


[Energy metabolism in patients with severe heart failure].

Schneeweiss B, Druml W, Graninger W, Grimm G, Laggner A, Lenz K, Kleinberger G.

Wien Klin Wochenschr. 1987 Oct 23;99(20):710-2. German.


Pharmacokinetics of ceftazidime and netilmicin in patients with sepsis.

Ganzinger U, Kleinberger G, Lenz K, Schatz F, Laggner A, Grimm G.

Int J Clin Pharmacol Ther Toxicol. 1987 Jul;25(7):354-62.


Reproducibility of thermal-dye lung water measurements by a lung water computer in critically ill patients.

Laggner AN, Lenz K, Druml W, Kleinberger G.

Crit Care Med. 1987 Jun;15(6):606-8.


Alterations of pharmacokinetic characteristics of antibiotics during sepsis: experimental and clinical data.

Ganzinger U, Kleinberger G, Lenz K, Grimm G, Laggner A, Haslberger A, Schatz F, Millendorfer A, Martindale JJ.

Chemioterapia. 1987 Jun;6(2 Suppl):246-8. No abstract available.


[Effect of high-dose prednisolone on lung fluid in patients with non-cardiogenic lung edema].

Laggner AN, Lenz K, Base W, Druml W, Schneeweiss B, Grimm G, Sommer G, Kleinberger G.

Wien Klin Wochenschr. 1987 Apr 3;99(7):245-9. German.


Loading and maintenance dose for the determination of amino acid kinetics in plasma.

Kleinberger G, Heinzel G, Druml W, Laggner A, Lenz K.

Infusionsther Klin Ernahr. 1987 Feb;14 Suppl 1:40-4.


[Assessment of liver function by metabolic parameters].

Kleinberger G.

Klin Anasthesiol Intensivther. 1987;34:46-58. German. No abstract available.


Dynamics of extravascular lung water in major burns.

Laggner AN, Lenz K, Sommer G, Druml W, Schneeweiss B, Grimm G, Kleinberger G.

Prog Clin Biol Res. 1987;236B:145-51. No abstract available.


Elimination of amino acids in chronic renal failure.

Druml W, Kleinberger G, Bürger U, Balcke P, Laggner A, Lenz K, Schmidt P, Zazgornik J.

Infusionsther Klin Ernahr. 1986 Dec;13(6):262-7.


Fructose-induced hyperlactemia in hyperosmolar syndromes.

Druml W, Kleinberger G, Lenz K, Laggner A, Schneeweiss B.

Klin Wochenschr. 1986 Jul 1;64(13):615-8.


[The effect of positive end-expiratory pressure (PEEP) on extravascular lung water in intensive care patients].

Laggner A, Lenz K, Druml W, Schneeweiss B, Kleinberger G.

Schweiz Med Wochenschr. 1986 Apr 26;116(17):565-9. German.


[Parenteral nutrition in liver insufficiency].

Kleinberger G.

Schweiz Med Wochenschr. 1986 Apr 26;116(17):545-9. German.


New aspects of parenteral nutrition with fat emulsions in injured patients.

Kleinberger G.

World J Surg. 1986 Feb;10(1):20-32. Review. No abstract available.


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