Center of Excellence on Neurodegeneration
The Center of Excellence on Neurodegeneration at Icahn School of Medicine in New York City focuses on basic mechanistic research and clinical trials in the areas of dementia (e.g., Alzheimer’s disease) and basal ganglia diseases (e.g., Parkinson’s disease, dystonias). The center is supported by a large center grant from the National Institute on Aging and numerous additional research grants from this and other Institutes of the National Institutes of Health.
Alzheimer’s disease and other forms of dementia
The Mount Sinai Alzheimer's Disease Research Center, a nationally renowned center founded in 1984, is a comprehensive basic molecular research facility and clinical assessment and trials program dedicated to the study of both normal aging and Alzheimer's disease.
Our team of experts in neuroscience, neuropathology, geriatrics, geriatric psychiatry and psychology, neurology, pathology, and radiology diagnoses those with memory disorders and provides crucial services for patients and their families.
In addition, our clinicians and neuroscientists conduct research into the causes of and treatments for Alzheimer’s disease and several other causes of dementia and sponsor educational programs for health care professionals and community groups.
Faculty dedicated to Alzheimer’s disease and other forms of dementias include:
Amy Aloysi (Psychiatry)
Michal Schnaider Beeri (Psychiatry)
Joseph Buxbaum (Psychiatry)
Michelle Ehrlich (Psychiatry)
Gregory Elder (Psychiatry)
Miguel Gama-Sosa (Psychiatry)
Sam Gandy (Neurology)
Tasos Georgakopoulos (Psychiatry)
Martin Goldstein (Neurology)
Hillel Grossman (Psychiatry)
Vahram Haroutunian (Psychiatry)
Patrick Hof (Neuroscience)
Effie Mitsis (Psychiatry)
Charles Mobbs (Neuroscience)
John Morrison (Neuroscience)
Judith Neugroschl (Psychiatry)
Giulio Pasinetti (Neurology)
Daniel Perl (Pathology)
Isak Prohovnik (Psychiatry)
Dushyant Purohit (Pathology)
Silvana Riggio (Psychiatry)
Nikolaos Robakis (Psychiatry)
Mary Sano (Psychiatry)
Corbett Schimming (Psychiatry)
James Schmeidler (Psychiatry)
Junichi Shioi (Psychiatry)
Jeremy Silverman (Psychiatry)
Basal ganglia neurobiology and disease
The basal ganglia are comprised of seven areas located deep in the brain, which are directly implicated in the pathophysiology of many common neurologic and psychiatric diseases. These include Parkinson’s disease, Huntington’s disease, and dystonia, all three of which are areas of active research at Icahn School of Medicine.
Parkinson’s disease is characterized by massive neurodegeneration of the dopaminergic neurons of the substantia nigra pars compacta, and Huntington’s disease is characterized by neurodegeneration of GABA-containing neurons in the caudate nucleus. Dystonia, albeit not a neurodegenerative disease, is caused by dysfunction within the basal ganglia, and likely also the cerebellum.
Research in Parkinson’s disease at Icahn School of Medicine includes the identification of both causative and risk factor genes and their pathogenic roles using transgenic, molecular, and cell biology methods.
Mount Sinai scientists have discovered new genes that cause Parkinson’s disease and are using mouse models to understand how these genetic variants lead to death of the brain’s dopamine-containing nerve cells. This work promises fundamental advances in both the diagnosis of Parkinson’s disease and its treatment
Autophagy in neurodegenerative diseases
Under active investigation is the role of autophagy in neurodegenerative diseases, including Parkinson’s disease. Autophagy is a highly regulated process by which cells ”eat” themselves and is implicated in several basal ganglia diseases.
The fundamental process of autophagy involves packing, trafficking, and delivering macromolecules and organelles through autophagic vacuoles to lysosomes for degradation. Autophagy is a ubiquitous cellular process that is linked to a variety of physiological functions and pathological conditions in mammals. Mount Sinai scientists are using cell imaging, protein biochemistry, structure biology, and genetic animal models to dissect the autophagic process in vitro and in vivo.
Research in Huntington’s disease focuses on possible uses of new therapeutic modalities, including latrepirdine, and the identification of cell autonomous versus non-cell autonomous mechanisms of dysfunction in the caudate nucleus and neocortex.
Mount Sinai scientists have identified fragments of the DARPP-32 gene, the most commonly used marker of the involved neurons, the medium spiny neurons (MSNs), which specifically direct transcription to the MSNs, and these researchers are using this gene as a tool both for the generation of novel mouse models of basal ganglia disease and for the study of the role of transcriptional dysregulation in Huntington’s disease.
Dystonia is a disease of the basal ganglia characterized by painful, involuntary twisting of different body parts. It is the third most common movement disorder in the United States. Several of the most severe childhood forms of dystonia are inherited as autosomal dominant traits with reduced penetrance (i.e., individuals can carry the disease gene but not express the trait). Mount Sinai scientists have identified the mutated genes for two forms of inherited dystonia, DYT1 and DYT6, and are searching for others. Center investigators are also generating mouse models for these dystonias and studying how the mutated proteins cause disease
Deep brain stimulation
Over the past decade, deep brain stimulation has revolutionized the treatment of basal ganglia disorders. In properly selected patients, deep brain stimulation markedly reduces motor fluctuations, eliminates medication-induced dyskinesia, improves gait, and decreases medication requirements. For many, the results of this surgery are life altering. Mount Sinai has played a major role in designing experiments to assess this therapy and in obtaining FDA approval for a range of basal ganglia disorders.
Faculty dedicated to basal ganglia neurobiology and disease include:
Catherine Cho (Neurology)
Michelle Ehrlich (Neurology)
Warren Olanow (Neurology)
Laurie Ozelius (Genetics and Genomic Sciences)
Michele Tagliati (Neurology)
Ruth Walker (Neurology)
Samuel Gandy, MD, PhD is the Chief for the Center of Excellence on Neurodegeneration, Professor of Neurology and Psychiatry.
Sam Gandy, MD, PhD
Mail/Ship c/o Enid Castro
Research Program Administrator
Department of Neurology
One Gustave L Levy Place, Box 1137
Annenberg Bldg, Rm 14-73
New York NY 10029