Giuseppina Tesco, M.D., Ph.D.

Associate Professor of Neuroscience, Alzheimer’s Disease Research Laboratory, Department of Neuroscience, Tufts University School of Medicine

Dr. Tesco’s group has shown how brain cell death caused by strokes or head injuries can lead to the production of amyloid-beta through the dysregulation of BACE levels in the brain. She identified a novel mechanism of regulation of BACE levels and activity by the trafficking molecule GGA3 (golgi-localized gamma-ear-containing ARF binding protein 3). More recently, Dr. Tesco’s laboratory has demonstrated the role of ubiquitin in the regulation of BACE1 degradation via the GGA pathway. This pathway may be a way to regulate beta-secretase activity therapeutically.

Funded Research

Project Description Researchers Funding
Functional Characterization of GGA3 Mutations Associated with Alzheimer’s Disease

Neurons, highly organized brain cells, are characterized by specialized projections called dendrites and axons. The axon is the longest neuronal projection where proteins move like along a highway, in two different directions and at different speeds. Scientists demonstrated that in the brain of subjects affected by Alzheimer’s disease (AD), a disorder characterized by memory loss, this coordinate traffic doesn’t work properly, so neurons start to be unhealthy and die.

Understand the Role of ADAM10 in the Pathogenesis of Alzheimer's Disease After Head Trauma

The goal of this project is to determine whether increased sAPPα levels are capable of reducing the production of neurotoxic Abeta following head trauma in order to reduce the risk of developing Alzheimer’s disease following brain injury.

TBI and Stroke Relationship to Alzheimer’s Disease

Investigating the increasingly documented link between TBI/stroke and Alzheimer’s disease is aimed not only at developing effective interruptions of that linkage but also a contribution to an understanding of the basic Alzheimer’s disease mechanism.


Selected Publications

These published papers resulted from Cure Alzheimer’s Fund support.
David Cantu, Kendall Walker, Lauren Andresen, Amaro Taylor-Weiner, David Hampton, Giuseppina Tesco and Chris G. Dulla, Traumatic Brain Injury Increases Cortical Glutamate Network Activity by Compromising GABAergic Control, Cereb. Cortex, March 7, 2014
Walker KR, Tesco G, Molecular mechanisms of cognitive dysfunction following traumatic brain injury, Front Aging Neurosci, 5(29), July 9, 2013
Kendall R. Walker, Eugene L. Kang, Michael J. Whalen, Yong Shen, and Giuseppina Tesco, Depletion of GGA1 and GGA3 Mediates Postinjury Elevation of BACE1, The Journal of Neuroscience, 32 (30), July 25, 2012, 10423–10437
Mannix RC, Zhang J, Park J, Zhang X, Bilal K, Walker K, Tanzi RE, Tesco G, Whalen MJ, Age-dependent effect of apolipoprotein E4 on functional outcome after controlled cortical impact in mice, Journal of Cerebral Blood Flow & Metabolism, 31, January 2011, 351–61
Gianni D, Li A, Tesco G, McKay KM, Moore J, Raygor K, Rota M, Gwathmey JK, Dec GW, Aretz T, Leri A, Semigran MJ, Anversa P, Macgillivray TE, Tanzi RE, delMonte F., Protein Aggregates and Novel Presenilin Gene Variants in Idiopathic Dilated Cardiomyopathy, Circulation: Journal of the American Heart Association, 121(10), Mar 16, 2010, 1216-26
Kim M, Suh J, Romano D, Truong MH, Mullin K, Hooli B, Norton D, Tesco G, Elliot K, Wagner SL, Moir RD, Becker KD, Tanzi RE., Potential late-onset Alzheimer's disease-associated mutations in the ADAM10 gene attenuate alpha-secretase activity., Human Molecular Genetics, Vol 18, Oct 15, 2009
Tesco G, Koh YH, Kang E, Cameron A, Das S, Sena-Esteves M, Hiltunen, Yang S-H, Zhong Z, Shen Y, Simpkins J, Tanzi RE., Depletion of GGA3 stabilizes BACE and enhances β-secretase activity, Neuron, 54(5), 2007, 721-37