Sylvain Lesne, PhD.

Assistant Professor, Department of Neuroscience


Research Interests:

Despite evidence for a pathogenic role of amyloid plaques and associated neuronal dystrophy, it has become apparent in the past decade that soluble, non-fibrillar amyloid-beta (Aβ) assemblies, also called Aβ oligomers, may represent the bioactive molecules involved in the physiopathology of Alzheimer's disease-related neuronal dysfunction and memory impairment.  However, the exact mechanism by which these multimeric forms are able to alter brain and neuronal function remains to be identified. The Lesne laboratory is examining whether and how Aβ oligomers can interact at neuronal plasma membranes with specific receptors involved in the cellular form of memory by combining biochemical and functional assays.

Our group also focuses on examining whether soluble Aβ oligomers represent the missing link between tau and amyloid pathologies in Alzheimer's disease. To this end, we use novel bigenic mice expressing the full human tau gene and APP, the precursor protein of Aβ. We investigate the effect of short- and long-term exposures of soluble Aβ oligomers on tau biology by integrating in vitro and in vivo approaches.

Lastly, the Lesne laboratory recently reported that soluble form(s) of alpha-synuclein (αSyn), usually linked to Parkinson’s disease, could play a central role in modulating the physiopathology of Alzheimer’s disease. New transgenic mouse models are under way to further validate the potential impact of αSyn in Alzheimer’s disease.

Selected Publications:

(For a comprehensive list of recent publications, refer to PubMed, a service provided by the National Library of Medicine.)

Lesné SE. Toxic oligomer species of amyloid-β in Alzheimer's disease, a timing issue. Swiss Med Wkly. 2014 Nov 6;144:w14021.

Fowler SW, Chiang AC, Savjani RR, Larson ME, Sherman MA, Schuler DR, Cirrito JR, Lesné SE, Jankowsky JL. Genetic modulation of soluble Aβ rescues cognitive and synaptic impairment in a mouse model of Alzheimer's disease. J Neurosci. 2014 Jun 4;34(23):7871-85.

Lesné SE, Sherman MA, Grant M, Kuskowski M, Schneider JA, Bennett DA, Ashe KH. Brain amyloid-β oligomers in ageing and Alzheimer's disease. Brain. 2013 May;136(Pt 5):1383-98.

Lesné SE. Breaking the Code of Amyloid-β Oligomers. Int J Cell Biol. 2013;2013:950783.

Larson M, Sherman MA, Amar F, Nuvolone M, Schneider JA, Bennett DA, Aguzzi A, Lesné SE. The complex PrP(c)-Fyn couples human oligomeric Aβ with pathological tau changes in Alzheimer's disease. J Neurosci. 2012 Nov 21;32(47):16857-71a.

Larson ME, Sherman MA, Greimel S, Kuskowski M, Schneider JA, Bennett DA, Lesné SE. Soluble α-Synuclein Is a Novel Modulator of Alzheimer's Disease Pathophysiology.J Neurosci. 2012 Jul 25;32(30):10253-66.

Larson ME, Lesné SE. Soluble Aβ oligomer production and toxicity. J Neurochem. 2012 Jan;120 Suppl 1:125-39.

Sherman MA, Lesné SE. Detecting aβ*56 oligomers in brain tissues. Methods Mol Biol. 2011;670:45-56.

Reed MN, Hofmeister JJ, Jungbauer L, Welzel AT, Yu C, Sherman MA, Lesné S, LaDu MJ, Walsh DM, Ashe KH, Cleary JP. Cognitive effects of cell-derived and synthetically derived Aβ oligomers. Neurobiol Aging. 2011 Oct;32(10):1784-94. Epub 2010 Jan 19.

Poling A, Morgan-Paisley K, Panos JJ, Kim EM, O'Hare E, Cleary JP, Lesné S, Ashe KH, Porritt M, Baker LE. Oligomers of the amyloid-beta protein disrupt working memory: confirmation with two behavioral procedures. Behav Brain Res. 2008 Nov 21;193(2):230-4.

Kotilinek LA, Westerman MA, Wang Q, Panizzon K, Lim GP, Simonyi A, Lesne S, Falinska A, Younkin LH, Younkin SG, Rowan M, Cleary J, Wallis RA, Sun GY, Cole G, Frautschy S, Anwyl R, Ashe KH. Cyclooxygenase-2 inhibition improves amyloid-beta-mediated suppression of memory and synaptic plasticity. Brain. 2008 Mar;131(Pt 3):651-64.

Lesné S, Kotilinek L, Ashe KH. Plaque-bearing mice with reduced levels of oligomeric amyloid-beta assemblies have intact memory function. Neuroscience. 2008 Feb 6;151(3):745-9. Epub 2007 Nov 17.

Venkitaramani DV, Chin J, Netzer WJ, Gouras GK, Lesne S, Malinow R, Lombroso PJ. Beta-amyloid modulation of synaptic transmission and plasticity. J Neurosci. 2007 Oct 31;27(44):11832-7. Review.

Cheng IH, Scearce-Levie K, Legleiter J, Palop JJ, Gerstein H, Bien-Ly N, Puoliväli J, Lesné S, Ashe KH, Muchowski PJ, Mucke L. Accelerating amyloid-beta fibrillization reduces oligomer levels and functional deficits in Alzheimer disease mouse models. J Biol Chem. 2007 Aug 17;282(33):23818-28.

Lesné S, Koh MT, Kotilinek L, Kayed R, Glabe CG, Yang A, Gallagher M, Ashe KH. A specific amyloid-beta protein assembly in the brain impairs memory. Nature. 2006 Mar 16;440(7082):352-7.

Ma H, Lesné S, Kotilinek L, Steidl-Nichols JV, Sherman M, Younkin L, Younkin S, Forster C, Sergeant N, Delacourte A, Vassar R, Citron M, Kofuji P, Boland LM, Ashe KH. Involvement of beta-site APP cleaving enzyme 1 (BACE1) in amyloid precursor protein-mediated enhancement of memory and activity-dependent synaptic plasticity. Proc Natl Acad Sci U S A. 2007 May 8;104(19):8167-72.

Townsend M, Cleary JP, Mehta T, Hofmeister J, Lesne S, O'Hare E, Walsh DM, Selkoe DJ. Orally available compound prevents deficits in memory caused by the Alzheimer amyloid-beta oligomers. Ann Neurol. 2006 Dec;60(6):668-76.

Lesné S, Koh MT, Kotilinek L, Kayed R, Glabe CG, Yang A, Gallagher M, Ashe KH. A specific amyloid-beta protein assembly in the brain impairs memory. Nature. 2006 Mar 16;440(7082):352-7.

Lesné S, Ali C, Gabriel C, Croci N, MacKenzie ET, Glabe C, Plotkine M, Marchand-Verrecchia C, Vivien D, Buisson A. NMDA-receptor activation inhibits alpha-secretase and promotes neuronal Abeta production. J Neurosci. 2005 Oct 12;25(41):9367-77.

Lesné S, Gabriel C, Nelson DA, White E, Mackenzie ET, Vivien D, Buisson A. Akt-dependent expression of NAIP-1 protects neurons against amyloid-{beta} toxicity. J Biol Chem. 2005 Jul 1;280(26):24941-7.

Lesné S, Docagne F, Gabriel C, Liot G, Lahiri DK, Buee L, Plawinski L, Delacourte A, MacKenzie ET, Buisson A, Vivien D. Transforming growth factor-beta 1 potentiates amyloid-beta generation in astrocytes and in transgenic mice. J Biol Chem. 2003 May 16;278(20):18408-18.

Current Graduate Students:

Fatou Amar (Ph.D. 2015, Neuroscience, University of Minnesota).

Susan Greimel (Ph.D. 2014, Neuroscience, University of Minnesota).