Schwartz Lab

Immunotherapy to combat
neurodegenerative diseases


Since 1998, when we first discovered, in contrast to the prevailing dogma at the time, that innate and adaptive immune cells are needed for central nervous system protection and repair, using animal models of acute and spinal cord injuries (1, 2), the team’s focus has been on brain-immune cross talk. Subsequent to this discovery, my team demonstrated that beyond their role in repair, blood-borne immune cells support life-long brain maintenance and plasticity(3, 4), and play a key role in coping with mental stress (5, 6).

Over the years, we demonstrated that monocyte-derived macrophages promote repair by homing to the damaged CNS where they display local anti-inflammatory activity (7), and that their homing to the damaged CNS, at least in part, is via selective CNS borders, including the leptomeninges adjacent to injury site, and the remote choroid plexus epithelium within the blood cerebrospinal fluid barrier (8). (9). These studies, in addition to many others, have been instrumental in advancing our comprehension of the immune system's role in brain aging (10, 11) and neurodegenerative diseases (12). They have revealed that in the aging process (10), and in various neurodegenerative diseases involving humans and mice, there is a breakdown in the cross-talk between the brain and the immune system. This breakdown is partially attributed to the chronic expression of Type-I interferon in the brain's choroid plexus, which has a detrimental impact on brain-immune communication, impairs microglial function, and diminishes the ability to manage inflammation (10, 11, 13, 14). 

Building on these findings and a plethora of other research, it has become evident that combatting chronic conditions of the brain necessitates sustained assistance from the immune system. We developed approach to enhance systemic immunity to help the brain to repair itself, by controlled blockade of the PD-1/PD-L1 inhibitory immune checkpoint (15-18). This approach is currently in clinical trial in AD patients, by ImmmunoBrain checkpoint biopharma. Our transformed understanding of brain immunity is summarized in recent articles (19-21).

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Research page

Selected Publications

N-acetylneuraminic acid links immune exhaustion and accelerated memory deficit in diet-induced obese Alzheimer’s disease mouse model

Suzzi S., Croese T., Ravid A., Gold O., Clark A. R., Medina S., Kitsberg D., Adam M., Vernon K. A., Kohnert E., Shapira I., Malitsky S., Itkin M., Brandis A., Mehlman T., Salame T. M., Colaiuta S. P., Cahalon L., Slyper M., Greka A., Habib N. & Schwartz M. (2023) Nature Communications. 14, 1, 1293.

Transforming the understanding of brain immunity

Castellani G., Croese T., Peralta Ramos J. M. & Schwartz M. (2023) Science. 380, 6640, eabo7649.

Cholesterol 24-hydroxylase at the choroid plexus contributes to brain immune homeostasis

Tsitsou-Kampeli A., Suzzi S., Kenigsbuch M., Satomi A., Strobelt R., Singer O., Feldmesser E., Purnapatre M., Colaiuta S. P., David E., Cahalon L., Hahn O., Wyss-Coray T., Shaul Y., Amit I. & Schwartz M. (2023) Cell Reports Medicine. 4, 11, 101278.

Alzheimer’s disease modification mediated by bone marrow-derived macrophages via a TREM2-independent pathway in mouse model of amyloidosis

Dvir-Szternfeld R., Castellani G., Arad M., Cahalon L., Colaiuta S. P., Keren-Shaul H., Croese T., Burgaletto C., Baruch K., Ulland T., Colonna M., Weiner A., Amit I. & Schwartz M. (2022) Nature Aging. 2, 1, p. 60-73

The brain-immune ecosystem: Implications for immunotherapy in defeating neurodegenerative diseases

Schwartz M., Abellanas M. A., Tsitsou-Kampeli A. & Suzzi S. (2022) Neuron. 110, 21, p. 3421-3424

A shared disease-associated oligodendrocyte signature among multiple CNS pathologies

Kenigsbuch M., Bost P., Halevi S., Chang Y., Chen S., Ma Q., Hajbi R., Schwikowski B., Bodenmiller B., Fu H., Schwartz M. & Amit I. (2022) Nature Neuroscience. 25, 7, p. 876-886

Immune cell compartmentalization for brain surveillance and protection

Croese T., Castellani G. & Schwartz M. (2021) Nature Immunology. 22, 9, p. 1083-1092

Disease-associated astrocytes in Alzheimer's disease and aging

Habib N., McCabe C., Medina S., Varshavsky M., Kitsberg D., Dvir-Szternfeld R., Green G., Dionne D., Nguyen L., Marshall J. L., Chen F., Zhang F., Kaplan T., Regev A. & Schwartz M. (2020) Nature Neuroscience. 23, 6, p. 701-706

PD-1/PD-L1 checkpoint blockade harnesses monocyte-derived macrophages to combat cognitive impairment in a tauopathy mouse model

Rosenzweig N., Dvir-Szternfeld R., Tsitsou-Kampeli A., Keren-Shaul H., Ben-Yehuda H., Weill-Raynal P., Cahalon L., Kertser A., Baruch K., Amit I., Weiner A. & Schwartz M. (2019) Nature Communications. 10, 465.

Mef2C restrains microglial inflammatory response and is lost in brain ageing in an IFN-I-dependent manner

Deczkowska A., Matcovitch-Natan O., Tsitsou-Kampeli A., Ben-Hamo S., Dvir-Szternfeld R., Spinrad A., Singer O., David E., Winter D. R., Smith L. K., Kertser A., Baruch K., Rosenzweig N., Terem A., Prinz M., Villeda S., Citri A., Amit I. & Schwartz M. (2017) Nature Communications. 8, 1, 717.

A Unique Microglia Type Associated with Restricting Development of Alzheimer's Disease

Keren-Shaul H., Spinrad A., Weiner A., Matcovitch-Natan O., Dvir-Szternfeld R., Ulland T. K., David E., Baruch K., Lara-Astaiso D., Toth B., Itzkovitz S., Colonna M., Schwartz M. & Amit I. (2017) Cell. 169, 7, p. 1276-1290.e17

PD-1 immune checkpoint blockade reduces pathology and improves memory in mouse models of Alzheimer's disease

Baruch K., Deczkowska A., Rosenzweig N., Tsitsou-Kampeli A., Sharif A. M., Matcovitch-Natan O., Kertser A., David E., Amit I. & Schwartz M. (2016) Nature Medicine. 22, 2, p. 135-137

Breaking immune tolerance by targeting Foxp3+ regulatory T cells mitigates Alzheimer's disease pathology

Baruch K., Rosenzweig N., Kertser A., Deczkowska A., Sharif A. M., Spinrad A., Tsitsou-Kampeli A., Sarel A., Cahalon L. & Schwartz M. (2015) Nat Commun. 6, 7967 (2015.

Aging-induced type I interferon response at the choroid plexus negatively affects brain function

Baruch K., Deczkowska A., David E., Castellano J. M., Miller O., Kertser A., Berkutzki T., Barnett Itzhaki I. Z., Bezalel D., Wyss-Coray T., Amit I. & Schwartz M. (2014) Science. 346, 6205, p. 89-93

CNS-specific immunity at the choroid plexus shifts toward destructive Th2 inflammation in brain aging

Baruch K., Ron Harel H. N., Gal H., Deczkowska A., Shifrut E., Ndifon W., Mirlas-Neisberg N., Cardon M., Vaknin I., Cahalon L., Berkutzki T., Mattson M. P., Gomez-Pinilla F., Friedman N. & Schwartz M. (2013) Proceedings of the National Academy of Sciences of the United States of America. 110, 6, p. 2264-2269

IFN-γ-dependent activation of the brain's choroid plexus for CNS immune surveillance and repair

Kunis G., Baruch K., Rosenzweig N., Kertser A., Miller O., Berkutzki T. & Schwartz M. (2013) Brain. 136, 11, p. 3427-3440

Recruitment of Beneficial M2 Macrophages to Injured Spinal Cord Is Orchestrated by Remote Brain Choroid Plexus

Shechter R., Miller O., Yovel G., Rosenzweig N., London A., Ruckh J., Kim K., Klein E., Kalchenko V., Bendel P., Lira S. A., Jung S. & Schwartz M. (2013) Immunity. 38, 3, p. 555-569

Infiltrating blood-derived macrophages are vital cells playing an anti-inflammatory role in recovery from spinal cord injury in mice

Shechter R., London A., Varol C., Raposo C., Cusimano M., Yovel G., Rolls A., Mack M., Pluchino S., Martino G., Jung S. & Schwartz M. (2009) PLoS Medicine. 6, 7, e1000113.

Toll-like receptors modulate adult hippocampal neurogenesis

Rolls A., Shechter R., London A., Ziv Y., Ronen A., Levy R. & Schwartz M. (2007) Nature Cell Biology. 9, 9, p. 1081–1088

Immune cells contribute to the maintenance of neurogenesis and spatial learning abilities in adulthood

Ziv Y., Ron N., Butovsky O., Landa G., Sudai E., Greenberg N., Cohen H., Kipnis J. & Schwartz M. (2006) Nature Neuroscience. 9, 2, p. 268-275

T cell deficiency leads to cognitive dysfunction: Implications for therapeutic vaccination for schizophrenia and other psychiatric conditions

Kipnis J., Cohen H., Cardon M., Ziv Y. & Schwartz M. (2004) Proceedings of the National Academy of Sciences of the United States of America. 101, 21, p. 8180-8185

Autoimmune T cells protect neurons from secondary degeneration after central nervous system axotomy

Moalem G., Leibowitz-Amit R., Yoles E., Mor F., Cohen I. R. & Schwartz M. (1999) Nature Medicine. 5, 1, p. 49-55

Implantation of stimulated homologous macrophages results in partial recovery of paraplegic rats

Rapalino O., Lazarov-Spiegler O., Agranov E., Velan G., Yoles E., Fraidakis M., Solomon A., Gepstein R., Katz A., Belkin M., Hadani M. & Schwartz M. (1998) Nature Medicine. 4, 7, p. 814-821
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