Sylvain Lesné, PhD, MSci

Professor, Department of Neuroscience

Professor, Department of Neuroscience

Institute for Translational Neuroscience Scholar

Graduate Program in Neuroscience


Research Summary/Interests

Abnormally aggregating proteins in cerebral brain tissues during the course of neurodegenerative disorders

Despite evidence for a pathogenic role of amyloid plaques and associated neuronal dystrophy, it has become apparent in recent years that soluble, non-fibrillar Amyloid-Beta assemblies, also called Abeta oligomers, are more critical than plaque load in the pathogenesis 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. Due to their size and presence in the extracellular space, our laboratory is examining whether and how Abeta oligomers can interact at neuronal plasma membranes with specific receptors involved in the cellular form of memory called long-term potentiation by combining biochemical and functional assays.

In addition, since Abeta has been suggested in 2001 to influence the formation of neurofibrillary tangles, composed of hyperphosphorylated tau proteins, our group also focuses on examining whether soluble Abeta oligomers represent the missing link between tau and amyloid pathologies in Alzheimer’s disease, using novel bigenic mice expressing the full human tau gene and APP, the precursor protein of Abeta. We investigate the effect of short- and long-term exposures of soluble Abeta oligomers on tau biochemistry, cellular localization and tau interaction with other microtubule-associated proteins by integrating in vitro and in vivo approaches using newly generated fluorescent protein-tagged knock-in transgenic mice crossed with transgenic mouse models of AD.


Singh, B, Covelo, A, Martell-Martínez, H, Nanclares, C, Sherman, MA, Okematti, E, Meints, J, Teravskis, PJ, Gallardo, C, Savonenko, AV, Benneyworth, MA, Lesné, SE, Liao, D, Araque, A & Lee, MK 2019, 'Tau is required for progressive synaptic and memory deficits in a transgenic mouse model of ?-synucleinopathy', Acta Neuropathologica, vol. 138, no. 4, pp. 551-574.

Khan, SS, LaCroix, M, Boyle, G, Sherman, MA, Brown, JL, Amar, F, Aldaco, J, Lee, MK, Bloom, GS & Lesné, SE 2018, 'Bidirectional modulation of Alzheimer phenotype by alpha-synuclein in mice and primary neurons' Acta Neuropathologica, vol. 136, no. 4, pp. 589-605.

Chiang, ACA, Fowler, SW, Reddy, R, Pletnikova, O, Troncoso, JC, Sherman, MA, Lesné, SE & Jankowsky, JL 2018, 'Discrete Pools of Oligomeric Amyloid-? Track with Spatial Learning Deficits in a Mouse Model of Alzheimer Amyloidosis' American Journal of Pathology, vol. 188, no. 3, pp. 739-756.

Larson, ME, Greimel, SJ, Amar, F, LaCroix, M, Boyle, G, Sherman, MA, Schley, H, Miel, C, Schneider, JA, Kayed, R, Benfenati, F, Lee, MK, Bennett, DA & Lesné, SE 2017, 'Selective lowering of synapsins induced by oligomeric ?-synuclein exacerbates memory deficits' Proceedings of the National Academy of Sciences of the United States of America, vol. 114, no. 23, pp. E4648-E4657.

Amar, F, Sherman, MA, Rush, T, Larson, M, Boyle, G, Chang, L, Götz, J, Buisson, A & Lesné, SE 2017, 'The amyloid-? oligomer A??56 induces specific alterations in neuronal signaling that lead to tau phosphorylation and aggregation' Science Signaling, vol. 10, no. 478, aal2021.

Sherman, MA, LaCroix, M, Amar, F, Larson, ME, Forster, C, Aguzzi, A, Bennett, DA, Ramsden, M & Lesné, SE 2016, 'Soluble conformers of A? and tau alter selective proteins governing axonal transport' Journal of Neuroscience, vol. 36, no. 37, pp. 9647-9658.

Alfonso, SI, Callender, JA, Hooli, B, Antal, CE, Mullin, K, Sherman, MA, Lesné, SE, Leitges, M, Newton, AC, Tanzi, RE & Malinow, R 2016, 'Gain-of-function mutations in protein kinase C? (PKC?) may promote synaptic defects in Alzheimer's disease' Science Signaling, vol. 9, no. 427, ra47.

Lesné, SE 2014, 'Toxic oligomer species of amyloid-? in Alzheimer's disease, a timing issue' Swiss Medical Weekly, vol. 144, 14021.

Fowler, SW, Chiang, ACA, Savjani, RR, Larson, ME, Sherman, MA, Schuler, DR, Cirrito, JR, Lesné, SE & Jankowsky, JL 2014, 'Genetic modulation of soluble A? rescues cognitive and synaptic impairment in a mouse model of Alzheimer's disease' Journal of Neuroscience, vol. 34, no. 23, pp. 7871-7885.

Lesné, SE 2013, 'Breaking the code of amyloid-? oligomers' International Journal of Cell Biology.