Sam Gandy, M.D., Ph.D.

Mount Sinai Endowed Chair in Alzheimer’s Disease Research; Professor of Neurology and of Psychiatry; Director, Mount Sinai Center for Wellness and Cognitive Health; Director, Mount Sinai NFL Center for Neurological Care
Icahn School of Medicine at Mount Sinai

 


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 250 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 M.D. 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

These projects were made possible from Cure Alzheimer's Fund support.

Selected Publications

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

Lane, R. F., St George-Hyslop, P., Hempstead, B. L., Small, S. A., Strittmatter, S. M., & Gandy, S. Vps10 family proteins and the retromer complex in aging-related neurodegeneration and diabetes, Journal of Neuroscience, October 10, 2012, Read More

Sproul, A. A., Jacob, S., Pre, D., Kim, S. H., Nestor, M. W., Navarro-Sobrino, M., Santa-Maria, I., Zimmer, M., Aubry, S., Steele, J. W., Kahler, D. J., Dranovsky, A., Arancio, O., Crary, J. F., Gandy, S., & Noggle, S. A. Characterization and molecular profiling of PSEN1 familial Alzheimer’s disease iPSC-derived neural progenitors, PLoS One, January 8, 2014, Read More

El Gaamouch, F., Audrain, M., Lin, W. J., Beckmann, N., Jiang, C., Hariharan, S., Heeger, P. S., Schadt, E. E., Gandy, S., Ehrlich, M. E., & Salton, S. R. VGF-derived peptide TLQP-21 modulates microglial function through C3aR1 signaling pathways and reduces neuropathology in 5xFAD mice, Molecular Neurodegenration, January 10, 2020, Read More

Beckmann, N. D., Lin, W. J., Wang, M., … Gandy, S., Tu, Z., Ehrlich, M. E., Zhang, B., Schadt, E. E. Multiscale causal networks identify VGF as a key regulator of Alzheimer’s disease, Nature Communications, August 7, 2020, Read More

Pan, A. L., Audrain, M., Sakakibara, E., Joshi, R., Zhu, X., Wang, Q., Wang, M., Beckmann, N. D., Schadt, E. E., Gandy, S., Zhang, B., Ehrlich, M. E., & Salton, S. R. Dual-Specificity Protein Phosphatase 4 (DUSP4) Overexpression Improves Learning Behavior Selectively in Female 5xFAD Mice, and Reduces β-Amyloid Load in Males and Females, Cells, December 1, 2022, Read More

Haure-Mirande, J. V., Audrain, M., Fanutza, T., Kim, S. H., Klein, W. L., Glabe, C., Readhead, B., Dudley, J. T., Blitzer, R. D., Wang, M., Zhang, B., Schadt, E. E., Gandy, S., & Ehrlich, M. E. Deficiency of TYROBP, an adaptor protein for TREM2 and CR3 receptors, is neuroprotective in a mouse model of early Alzheimer’s pathology, Acta Neuropathologica, June 13, 2017, Read More

Steele, J. W., Ju, S., Lachenmayer, M. L., Liken, J., … Gandy, S. Latrepirdine stimulates autophagy and reduces accumulation of alpha-synuclein in cells and in mouse brain, Molecular Psychiatry, August 7, 2012, Read More

Gandy S. News & views: anti-amyloid antibodies and novel emerging approaches to Alzheimer’s disease in 2023, Molecular Neurodegeneration, September 25, 2023, Read More

Steele, J. W., Lachenmayer, M. L., … Gandy, S. Latrepirdine improves cognition and arrests progression of neuropathology in an Alzheimer’s mouse model, Molecular Psychiatry, July 31, 2012, Read More

Readhead, B., Haure-Mirande, J. V., Zhang, B., Haroutunian, V., Gandy, S., Schadt, E. E., Dudley, J. T., & Ehrlich, M. E. Molecular systems evaluation of oligomerogenic APP(E693Q) and fibrillogenic APP(KM670/671NL)/PSEN1(Δexon9) mouse models identifies shared features with human Alzheimer’s brain molecular pathology, Molecular Psychiatry, November 10, 2015, Read More

Lublin, A. L., & Gandy, S. Amyloid-beta Oligomers: Possible Roles as Key Neurotoxins in Alzheimer’s Disease, Mount Sinai Journal of Medicine, January 25, 2010, Read More

DeKosky, S. T., Blennow, K., Ikonomovic, M. D., & Gandy, S. Acute and traumatic encephalopathies: pathogenesis and biomarkers, Nature Reviews Neurology, April 1, 2013, Read More

Mitsis, E. M., Riggio, S., … Gandy, S. Tauopathy PET and amyloid PET in the diagnosis of chronic traumatic encephalopathies: studies of a retired NFL player and of a man with FTD and severe head injury, Translational Psychiatry, September 16, 2014, Read More

Gandy, S., & Ehrlich, M. E. miR155, TREM2, INPP5D: Disease stage and cell type are essential considerations when targeting clinical interventions based on mouse models of Alzheimer’s amyloidopathy, Journal of Neuroinflammation, September 25, 2023, Read More

Kim, S. H., Steele, J. W., Lee, S. W., Clemenson, G. D., Carter, T. A., Treuner, K., Gadient, R., Wedel, P., Glabe, C., Barlow, C., Ehrlich, M. E., Gage, F. H., & Gandy, S. Proneurogenic Group II mGluR antagonist improves learning and reduces anxiety in Alzheimer A beta oligomer mouse, Molecular Psychiatry, August 12, 2014, Read More

Audrain, M., Haure-Mirande, J. V., Wang, M., Kim, S. H., Fanutza, T., Chakrabarty, P., Fraser, P., St George-Hyslop, P. H., Golde, T. E., Blitzer, R. D., Schadt, E. E., Zhang, B., Ehrlich, M. E., & Gandy, S. Integrative approach to sporadic Alzheimer’s disease: deficiency of TYROBP in a tauopathy mouse model reduces C1q and normalizes clinical phenotype while increasing spread and state of phosphorylation of tau, Molecular Psychiatry, October 3, 2018, Read More

Ruiz, H. H., Chi, T., Shin, A. C., Lindtner, C., Hsieh, W., Ehrlich, M., Gandy, S., & Buettner, C. Increased susceptibility to metabolic dysregulation in a mouse model of Alzheimer’s disease is associated with impaired hypothalamic insulin signaling and elevated BCAA levels, Alzheimer's & Dementia, February 28, 2016, Read More

Gandy, S., Ikonomovic, M. D., Mitsis, E., Elder, G., Ahlers, S. T., Barth, J., Stone, J. R., & DeKosky, S. T. Chronic traumatic encephalopathy: clinical biomarker correlations and current concepts in pathogenesis, Molecular Neurodegeneration, September 17, 2014, Read More

Mitsis, E. M., Bender, H. A., Kostakoglu, L., Machac, J., Martin, J., Woehr, J. L., Sewell, M. C., Aloysi, A., Goldstein, M. A., Li, C., Sano, M., & Gandy, S. A consecutive case series experience with [18 F] florbetapir PET imaging in an urban dementia center: impact on quality of life, decision making, and disposition, Molecular Neurodegeneration, February 3, 2014, Read More

Lane, R. F., Steele, J. W., Cai, D., Ehrlich, M. E., Attie, A. D., & Gandy, S. Protein sorting motifs in the cytoplasmic tail of SorCS1 control generation of Alzhiemer’s amyloid beta peptide, Journal of Neuroscience, April 17, 2013, Read More

Bharadwaj, P. R., Verdile, G., Barr, R. K., Gupta, V., Steele, J. W., Lachenmayer, M. L., Yue, Z., Ehrlich, M. E., Petsko, G., Ju, S., Ringe, D., Sankovich, S. E., Caine, J. M., Macreadie, I. G., Gandy, S., & Martins, R. N. Latrepirdine (dimebon) enhances autophagy and reduces intracellular GFP-Aβ42 levels in yeast, Journal of Alzheimer's Disease, November 14, 2012, Read More

Gandy S. Alzheimer’s disease: new data highlights nonneuronal cell types and the necessity for presymptomatic prevention strategies., Biological Psychiatry, November 28, 2013, Read More

Gandy S. Open peer commentary on “Prescribing anti‐amyloid immunotherapies to treat Alzheimer’s disease: Fully informing patient decisions”, Alzheimer's & Dementia, November 20, 2023, Read More

Moreno, C. L., Della Guardia, L., Shnyder, V., Ortiz-Virumbrales, M., Kruglikov, I., Zhang, B., Schadt, E. E., Tanzi, R. E., Noggle, S., Buettner, C., & Gandy, S. iPSC-derived familial Alzheimer’s PSEN2 N141I cholinergic neurons exhibit mutation-dependent molecular pathology corrected by insulin signaling, Molecular Neurodegeneration, June 26, 2018, Read More

Lane, R. F., Raines, S. M., Steele, J. W., Ehrlich, M. E., Lah, J. A., Small, S. A., Tanzi, R. E., Attie, A. D., & Gandy, S. Diabetes-associated SorCS1 regulates Alzheimer’s amyloid-beta metabolism: evidence for involvement of SorL1 and the Retromer Complex, Journal of Neuroscience, September 29, 2010, Read More

Hunsberger, J. G., Rao, M., Kurtzberg, J., Bulte, J. W. M., Atala, A., LaFerla, F. M., Greely, H. T., Sawa, A., Gandy, S., Schneider, L. S., & Doraiswamy, P. M. Accelerating Stem Cell Trials for Alzheimer’s Disease, Lancet Neurology, December 17, 2015, Read More

Kim, S. H., Fraser, P. E., Westaway, D., St George-Hyslop, P. H., Ehrlich, M. E., & Gandy, S. Group II metabotropic glutamate receptor stimulation triggers production and release of Alzheimer’s amyloid beta (42) from isolated intact nerve terminals, Journal of Neuroscience, March 17, 2010, Read More

Knight, E. M., Kim, S. H., Kottwitz, J. C., Hatami, A., Albay, R., Suzuki, A., Lublin, A., Alberini, C. M., Klein, W. L., Szabo, P., Relkin, N. R., Ehrlich, M., Glabe, C. G., Gandy, S., & Steele, J. W. Effective anti-Alzheimer A beta therapy involves depletion of specific A beta oligomer subtypes, Neurology Neuroimmunology & Neuroinflammation, May 10, 2016, Read More

Ortiz-Virumbrales, M., Moreno, C. L., Kruglikov, I., Marazuela, P., Sproul, A., Jacob, S., Zimmer, M., Paull, D., Zhang, B., Schadt, E. E., Ehrlich, M. E., Tanzi, R. E., Arancio, O., Noggle, S., & Gandy, S. CRISPR/Cas9- Correctable mutation-related molecular and physiological phenotypes in iPSC-derived Alzheimer’s PSEN (N141l) neurons, Acta Neuropathologica Communications, October 27, 2017, Read More

Steele, J. W., Kim, S. H., Cirrito, J. R., Verges, D. K., Restivo, J. L., Westaway, D., Fraser, P., Hyslop, P. S., Sano, M., Bezprozvanny, I., Ehrlich, M. E., Holtzman, D. M., & Gandy, S. Acute dosing of latrepirdine (Dimebon), a possible Alzheimer therapeutic, elevates extracellular amyloid-beta levels in vitro and in vivo, Molecular Neurodegeneration, December 17, 2009, Read More

T., Kim, S. H., Heja, S., Readhead, B., Dudley, J. T., Blitzer, R. D., Schadt, E. E., Zhang, B., Gandy, S., & Ehrlich, M. E. Integrative approach to sporadic Alzheimer’s disease: deficiency of TYROBP in cerebral Aβ amyloidosis mouse normalizes clinical phenotype and complement subnetwork molecular pathology without reducing Aβ burden, Molecular Psychiatry, October 3, 2018, Read More

Haure-Mirande, J. V., Audrain, M., Ehrlich, M. E., & Gandy, S. Microglial TYROBP/DAP12 in Alzheimer’s disease: Transduction of physiological and pathological signals across TREM2, Molecular Neurodegeneration, August 24, 2022, Read More

Gandy, S., Simon, A. J., Steele, J. W., Lublin, A. L., Lah, J. J., Walker, L. C., Levey, A. I., Krafft, G. A., Levy, E., Checler, F., Glabe, C., Bilker, W. B., Abel, T., Schmeidler, J., & Ehrlich, M. E. Days to criterion as an indicator of toxicity associated with Human Alzheimer Amyloid-beta Oligomers, Annals of Neurology, August 1, 2010, Read More

Knight, E. M., Ruiz, H. H., Kim, S. H., Harte, J. C., Hsieh, W., Glabe, C., Klein, W. L., Attie, A. D., Buettner, C., Ehrlich, M. E., & Gandy, S. Unexpected partial correction of metabolic and behavioral phenotypes of Alzheimer’s APP/PSEN1 mice by gene targeting of diabetes/Alzheimer’s-related Sorcs1, Acta Neuropathologica Communications, February 25, 2016, Read More

Castranio, E. L., Hasel, P., Haure-Mirande, J. V., Ramirez Jimenez, A. V., Hamilton, B. W., Kim, R. D., Glabe, C. G., Wang, M., Zhang, B., Gandy, S., Liddelow, S. A., & Ehrlich, M. E. Microglial INPP5D limits plaque formation and glial reactivity in the PSAPP mouse model of Alzheimer’s disease, Alzheimer's & Dementia, November 30, 2022, Read More