Sam Gandy, M.D.

Sinai Professor of Alzheimer’s Disease Research, Mount Sinai School of Medicine, New York
Associate Director of the Mount Sinai Alzheimer’s Disease Research Center
Chairman, National Medical and Scientific Advisory Council of the Alzheimer’s Association

Dr. Gandy is an international expert in the metabolism of the sticky substance called amyloid that clogs the brain in patients with Alzheimer’s. In 1989, Gandy and his team discovered the first drugs that could lower formation of amyloid. Dr. Gandy has written more than 150 original papers, chapters and reviews on this topic. Dr. Gandy has received continuous NIH funding for his research on amyloid metabolism since 1986. In work that is being prepared for publication and that forms the basis for his nomination to the Cure Alzheimer’s Fund Consortium, Dr. Gandy and his colleague, Dr. Michelle Ehrlich (Professor of Neurology, Pediatrics and Genetics at Mount Sinai School of Medicine) have created a highly novel transgenic mouse that accumulates Aβ oligomers in the brain and develops memory problems but never develops amyloid “plaques” during its entire lifetime.

Dr. Gandy received his MD and Ph.D. at the Medical University of South Carolina. He did his postgraduate work at the Columbia University College of Physicians & Surgeons and Cornell University Medical College. Dr. Gandy completed his post doctorate at The Rockefeller University, where he was appointed assistant professor in the laboratory of Paul Greengard, 2000 Laureate of the Nobel Prize in Physiology or Medicine. Gandy was appointed associate professor of neurology and neurosciences at Cornell University Medical College in 1992. In 1997, he moved to New York University where he served as professor of psychiatry and cell biology until his appointment as Paul C. Brucker, M.D., Professor of Neuroscience at Jefferson Medical College and Director of the Farber Institute for Neurosciences in 2001. In July 2007, he assumed his current post as Sinai Professor of Alzheimer’s Disease Research at the Mount Sinai School of Medicine.

Funded Research

Project Description Researchers Funding
Stem Cell Consortium

Stem cells are the least mature cells in the body. Because these cells are so immature, they can be treated with a defined cocktail of factors and, depending on which factors are used and in what sequence, those factors can cause maturation of cells along discrete cell types. With a new tool called induced pluripotent stem cells, it now is possible to take skin cells from adults and return them to this immature state. By redirecting skin cells from Alzheimer’s patients and turning them into nerve cells, we are able to study adult Alzheimer’s neurons (nerve cells) in the lab.

2013
$600,000
Brain Structure, Abeta Metabolism and Behavior in Mice Deficient in Diabetes and Alzheimer's Associated SorCS1

This is an extension of an earlier grant. SorCS1 and SorL1/SorLA/LR11 belong to the sortilin family of vacuolar protein sorting-10 (Vps10) domain-containing proteins. Both are genetically associated with Alzheimer’s disease (AD), and SORL1 expression is decreased in the brains of patients suffering from AD. SorCS1 also is associated genetically with Types 1 and 2 diabetes mellitus (T1DM, T2DM).

2010 to 2012
$100,000
ADAM10 and Dimebolin

Understanding the hypothesized relationship between ADAM10, a newly identified Alzheimer’s-related gene, and dimebolin, the key ingredient in the anti-Alzheimer’s drug Dimebon.

2009
$150,000

Selected Publications

These published papers resulted from Cure Alzheimer’s Fund support.

Andrew A. Sproul, Samson Jacob, Deborah Pre, Soong Ho Kim, Michael W. Nestor, Miriam Navarro-Sobrino, Ismael Santa-Maria, Matthew Zimmer, Soline Aubry, John W. Steele, David J. Kahler, Alex Dranovsky, Ottavio Arancio, John F. Crary, Sam Gandy, and Scott A. Noggle, Characterization and Molecular Profiling of PSEN1 Familial Alzheimer's Disease iPSC-Derived Neural Progenitors, PLoS ONE, 9(1), Jan 8 2014
J W Steele, M L Lachenmayer, S Ju, A Stock, J Liken, S H Kim, L M Delgado, I E Alfaro, S Bernales, G Verdile, P Bharadwaj, V Gupta, R Barr, A Friss, G Dolios, R Wang, D Ringe, P Fraser, D Westaway, P H St George-Hyslop, P Szabo, N R Relkin, J D Buxbaum, C G Glabe, A A Protter, R N Martins, M E Ehrlich, G A Petsko, Z Yue and S Gandy, Latrepirdine improves cognition and arrests progression of neuropathology in an Alzheimer's mouse model, Mol Psychiatry, 18(8), Aug 2013, 889-897
Steele JW, Ju S, Lachenmayer ML, Liken J, Stock A, Kim SH, Delgado LM, Alfaro IE, Bernales S, Verdile G, Bharadwaj P, Gupta V, Barr R, Friss A, Dolios G, Wang R, Ringe D, Protter AA, Martins RN, Ehrlich ME, Yue Z, Petsko GA, Gandy S, Latrepirdine stimulates autophagy and reduces accumulation of α-synuclein in cells and in mouse brain, Mol Psychiatry, 18(8), August 2013, 882-888
Lane RF, Steele JW, Cai D, Ehrlich ME, Attie AD, Gandy S, Protein Sorting Motifs in the Cytoplasmic Tail of SorCS1 Control Generation of Alzheimer's Amyloid-β Peptide, J Neurosci, 33(16), April 17, 2013, 7099-7107
Steven T. DeKosky, Kaj Blennow, Milos D. Ikonomovic & Sam Gandy, Traumatic Brain Injury (TBI) can lead to Neurodegenerative Syndromes that include Alzheimer Disease (AD) and Chronic Traumatic Encephalopathy (CTE), Nature Reviews Neurology, Volume 9, No 4 , April 2013, 192-200
Steven T. DeKosky, Kaj Blennow, Milos D. Ikonomovic & Sam Gandy, Acute and chronic traumatic encephalopathies: pathogenesis and biomarkers, Nature Reviews Neurology, April 2013, 192-200
Soong Ho Kim1, Elysse M Knight, Eric L Saunders, Azita K Cuevas, Marusia Popovech, Lung-Chi Chen, Sam Gandy, Rapid doubling of Alzheimer’s amyloid-β40 and 42 levels in brains of mice exposed to a nickel nanoparticle model of air pollution, F1000Research, 1:70, Dec 21, 2012
Rachel F. Lane, Peter St George-Hyslop, Barbara L. Hempstead, Scott A. Small, Stephen M. Strittmatter, and Sam Gandy, Vps10 Family Proteins and the Retromer Complex in Aging-Related Neurodegeneration and Diabetes, The Journal of Neuroscience, 32(41), October 10, 2012, 14080 –14086
Gandy S, Simon AJ, Steele JW, Lublin AL, Lah JJ, Walker LC, Levey AI, Krafft GA, Levy E, Checler F, Glabe C, Bilker WB, Abel T, Schmeidler J, Ehrlich ME, Days to criterion as an indicator of toxicity associated with human Alzheimer amyloid-β oligomers, Annals of Neurology, Volume 68, Issue 2, August 2010
Kim SH, Fraser PE, Westaway D, George-Hyslop PH, Ehrlich ME, Gandy S, Group II Metabotropic Glutamate Receptor Stimulation Triggers Production and Release of Alzheimer's Amyloid β42 from Isolated Intact Nerve Terminals, The Journal of Neuroscience, 30(11), Mar 17, 2010, 3870-3875
Lublin AL, Gandy S, Amyloid-β Oligomers: Possible Role as Key Neurotoxins in Alzheimer's Disease, Mount Sinai Joural of Medicine, 77, January 2010, 43-9
Hata S, Fujishige S, Araki Y, Kato N, Araseki M, Nishimura M, Hartmann D, Saftig P, Fahrenholz F, Taniguchi M, Urakami K, Akatsu H, Martins R, Yamamoto K, Maeda M, Yamamoto T, Nakaya T, Gandy S, Suzuki T, Alcadein cleavages by amyloid beta-precursor protein (APP) alpha- and gamma-secretases generate small peptides, p3-Alcs, indicating Alzheimer disease-related gamma-secretase dysfunction, The Journal of Biological Chemistry, 284(52), Dec 25, 2009, 36024-33
Steele JW, Kim HS, Cirrito JR, Verges DK, Restivo JL, Westaway D, Fraser P, Hyslop PSG, Sano M, Bezprozvanny I, Ehrlich ME, Holtzman DM, Gandy S, Acute dosing of latrepirdine (Dimebon), a possible Alzheimer therapeutic, elevates extracellular amyloid-beta levels in vitro and in vivo, Molecular Neurodegeneration, 4:51, Dec 17, 2009
Kaufer D, Gandy S., APOE ε4 and bapineuzumab: Infusing pharmacogenomics into Alzheimer disease therapeutics, Neurology, 73(24), Dec 15, 2009, 2052-3