Levy Lab

Changes in Vesicular Trafficking in Alzheimer’s Disease Neurons

Research in the Levy Lab, led by Efrat Levy, PhD, aims to understand the pathogenic processes that lead to AD and related neurodegenerative disease. Inrecent years, our focus has been on changes in vesicular trafficking in neurons during the disease, including what are now foundational studies of the role of extracellular vesicles as either protective or pathogenic vehicles within the brain. Our findings suggest that the secretion of extracellular vesicles is a mechanism for the clearance of accumulated material when disease-mediated dysfunctions prevent the efficient transport of cargo for degradation inside the cell. Ongoing studies are investigating the effects of neuronal abnormalities on extracellular vesicles secretion and the utilization of extracellular vesicles as protective vehicles. Extracellular vesicles transport their content for long distances through the extracellular space and into recipient cells and can deliver protective proteins and other molecules, providing a novel therapeutic approach for AD. We are currently studying the brain of AD patients and mouse models to determine the role of the generation and secretion of extracellular vesicles in either protection or pathogenicity in the disease. In one project, we are investigating the enhanced release of extracellular vesicles as a potential therapy, preventing neuronal loss in the brain due to accumulation of toxic material. We are also studying the apolipoprotein E (APOE) genotype, an important determinant of an individual’s risk for developing AD. While the APOE2 allele appears to be protective, APOE4 increases the risk for the disease as compared with carriers of the neutral-risk APOE3 allele. Additionally, APOE4 expression can lead to cognitive decline during aging that is independent of characteristic AD pathology.

We are also studying the apolipoprotein E (APOE) genotype, an important determinant of an individual’s risk for developing AD. While the APOE2 allele appears to be protective, APOE4 increases the risk for the disease as compared with carriers of the neutral-risk APOE3 allele. Additionally, APOE4 expression can lead to cognitive decline during aging that is independent of characteristic AD pathology.

Our data show neuronal abnormality in the brain of APOE4 carriers and lower levels of extracellular vesicles released into the brain extracellular space. Compromised vesicle production is likely to have adverse effects, diminishing a cell’s ability to eliminate accumulated toxic material, leading to neuron vulnerability in APOE4-expressing individuals. Extracellular vesicular dysfunction is a previously unappreciated component of the brain pathologies that occur as a result of APOE4 expression, contributing to higher risk of developing AD. We are currently investigating the changes in the brain of carriers of APOE4 allele as compared with the APOE2 allele to identify therapeutic targets based on the differences in release and content of extracellular vesicles due to the different APOE genotypes. Our translational research also involves the delivery of proteins and peptides that prevent the development of AD via extracellular vesicles.

Publications

All publications

Levy Lab Members

Gisele Adrian Ferrari -Adminstrator
845-398-5539 Gisele.Ferrari@NKI.rfmh.org
Gisele Ferrari joined the Center of Dementia Research as a Project Administrator in January 2007. She coordinates and oversees grant applications for the laboratories of Drs. Levy, Mathews, and Ginsberg, and a Core facility. Her expanded duties include independently generating budgets and additional form pages; she is responsible for ongoing grant management, expenditures, and budgetary compliance; and she oversees laboratory personnel. This is in addition to her obligations to the Institutional Biosafety Committee (IBC).

Bryana Barreto
845-398-6669 Bryana.Barreto@nki.rfmh.org
Bryana Barreto graduated from New York University, College of Arts and Science, New York, NY, with a BS in May 2018. She joined the laboratory of Dr. Levy in October 2018 as a Research Support Assistant. Her main research focus is the role of extracellular vesicles in neurodegenerative disorders, such as Alzheimer’s disease and Down syndrome.

Steven DeRosa
845-398-5533 Steven.DeRosa@NKI.rfmh.org
Steven DeRosa graduated from Rutgers University, School of Engineering, New Brunswick, NJ with a BS in May 2000. He is an Assistant Research Scientist maintaining and genotyping mouse models in neurodegenerative disorders, such as Alzheimer’s disease and Down syndrome.

Pasquale D'Acunzo, PhD
845-398-6669 Pasquale.DAcunzo@NKI.rfmh.org
Dr. D'Acunzo graduated from the University of Milan, Milan, Italy with a BS and MS and obtained his PhD from the University of Rome “Tor Vergata”, Rome, Italy. He joined the laboratory of Dr. Levy in July 2018 as an Assistant Research Scientist and a postdoctoral fellow at the Department of Psychiatry at New York University Langone Medical Center. Integrating his expertise in mitochondria functions and the laboratory’s focus on neurodegenerative disorders, he is investigating the release of mitochondrial proteins into the extracellular space of brains of Alzheimer’s disease and Down syndrome patients

Sasmita Das, PhD
845-398-6669 Sasmita.Das@NKI.rfmh.org
Dr. Das graduated from the Utkal University, India with a BS, MS and PhD. She joined the laboratory of Dr. Levy in December 2017 as a Research Support Assistant. She is involved in maintenance, genotyping, as well as immunohistochemical and biochemical analyses of mouse models of neurodegenerative disorders, such as Alzheimer’s disease and Down syndrome.

Adaora Aroh
845-398-6669 Adaora.Aroh@NKI.rfmh.org
Adaora Aroh graduated from Pace University, New York, NY with a MS in May 2020. She joined the laboratory of Dr. Levy in August 2020 as a Research Support Assistant. Her main research focus is the role of extracellular vesicles in neurodegenerative disorders, such as Alzheimer’s disease and Down syndrome.

Yohan Kim, PhD
845-398-6669 Yohan.Kim@NKI.rfmh.org
Dr. Kim graduated from Jeju National University, Jeju, South Korea with a BS, Eastern Washington University, Cheney, WA with MS, and obtained his PhD from the University of Iowa, Iowa, IA. He joined the laboratory of Dr. Levy in July 2018 as an Assistant Research Scientist and a postdoctoral fellow at the Department of Psychiatry at New York University Langone Medical Center. His main research interest is the role of extracellular vesicles in neurodegenerative disorders, such as Alzheimer’s disease and Down syndrome.

Mathew Rios
845-398-6669 Mathew.Rios@NKI.rfmh.org
Matthew Rios graduated from Binghamton University, Binghamton, NY, with a BA in May 2016. He joined the laboratory of Dr. Levy in May 2020 as a Research Support Assistant. His main research focus is the role of extracellular vesicles in neurodegenerative disorders, such as Alzheimer’s disease and Down syndrome.

Monika Pawlik, PhD
845-398-6664 Monika.Pawlik@NKI.rfmh.org
Dr. Pawlik graduated from University of Koln, Koln Germany with a BS and obtained her PhD from the Freie University of Berlin, Berlin, Germany. She is the director of the Animal Core for the Program Project of Drs. Nixon, Ginsberg, Mathews, and Levy. She manages a large colony of mice essential to the research programs in the four laboratories, colonies that include transgenic and knockout mouse lines and complex crosses between these lines, mouse models of neurodegenerative disorders, such as Alzheimer’s disease and Down syndrome.

 

Kathy Peng, PhD
845-398-5439 Kathy.Peng@NKI.rfmh.org
Dr. Peng graduated from Johns Hopkins University, Baltimore, MD with a BS and obtained her PhD from New York University Langone Medical center. She is an investigator in the laboratories of Drs. Levy and Mathews at the Center for Dementia Research and is a postdoctoral fellow at the Department of Psychiatry at New York University Langone Medical Center. She is currently focusing on delineating the molecular mechanisms involved in the neuronal endosomal and exosomal changes in the brain of carriers of the apolipoprotein E4 gene, the greatest genetic risk factor for Alzheimer’s disease, as compared with the neutral apolipoprotein E3 gene carriers.

Lital Rachmany Raber, PhD
845-398-6669 Lital.RachmanyRaber@NKI.rfmh.org
Dr. Rachmany Raber graduated from Bar-Ilan University, Tel Aviv, Israel with BS, and from Tel Aviv University, Tel Aviv, Israel with a MS and PhD. She joined the laboratory of Dr. Levy in July 2018 as an Assistant Research Scientist at the Center for Dementia Research and a postdoctoral fellow at the Department of Psychiatry at New York University Langone Medical Center. Her main research interest is the role of extracellular vesicles in neurodegenerative disorders, such as Alzheimer’s disease.

Michelle Kurz
845-398-6669 Michelle.Kurz@NKI.rfmh.org
Michelle Kurz graduated from Skidmore College with a BS in May 2019 and joined the Levy laboratory in July 2019. She is a Research Support Assistant whose main research focus is the role of extracellular vesicles in neurodegenerative disorders, such as Alzheimer's disease and Down syndrome.

Jonathan Ungania
845-398-6669 Jonathan.Ungania@NKI.rfmh.org
Jonathan Ungania graduated from Mercy College with a BS in May 2020 and joined the Levy laboratory in October 2020. He is a Research Support Assistant whose main research focus is the role of extracellular vesicles in neurodegenerative disorders, such as Alzheimer's disease and Down syndrome.

Taylor Hendrickson
845-398-6669 Taylor.Hendrickson@NKI.rfmh.org
Taylor Hendrickson graduated from SUNY College of Environmental Science and Forestry with a BS in December 2016 and joined the Levy laboratory in November 2020. She is a Research Support Assistant whose main research focus is the role of extracellular vesicles in neurodegenerative disorders, such as Alzheimer's disease and Down syndrome.