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α-Synuclein modulates tau spreading in mouse brains.
J Exp Med. 2021 01 04; 218(1)JE

Abstract

α-Synuclein (α-syn) and tau aggregates are the neuropathological hallmarks of Parkinson's disease (PD) and Alzheimer's disease (AD), respectively, although both pathologies co-occur in patients with these diseases, suggesting possible crosstalk between them. To elucidate the interactions of pathological α-syn and tau, we sought to model these interactions. We show that increased accumulation of tau aggregates occur following simultaneous introduction of α-syn mousepreformed fibrils (mpffs) and AD lysate-derived tau seeds (AD-tau) both in vitro and in vivo. Interestingly, the absence of endogenous mouse α-syn in mice reduces the accumulation and spreading of tau, while the absence of tau did not affect the seeding or spreading capacity of α-syn. These in vivo results are consistent with our in vitro data wherein the presence of tau has no synergistic effects on α-syn. Our results point to the important role of α-syn as a modulator of tau pathology burden and spreading in the brains of AD, PDD, and DLB patients.

Authors+Show Affiliations

The Department of Pathology and Laboratory Medicine, Institute on Aging and Center for Neurodegenerative Disease Research, the Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA. AbbVie, Foundational Neuroscience Center, Cambridge, MA.The Department of Pathology and Laboratory Medicine, Institute on Aging and Center for Neurodegenerative Disease Research, the Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA.The Department of Pathology and Laboratory Medicine, Institute on Aging and Center for Neurodegenerative Disease Research, the Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA.The Department of Pathology and Laboratory Medicine, Institute on Aging and Center for Neurodegenerative Disease Research, the Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA.The Department of Pathology and Laboratory Medicine, Institute on Aging and Center for Neurodegenerative Disease Research, the Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA.The Department of Pathology and Laboratory Medicine, Institute on Aging and Center for Neurodegenerative Disease Research, the Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA.The Department of Cancer Biology and Abramson Family Cancer Research Institute, the Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA.The Department of Pathology and Laboratory Medicine, Institute on Aging and Center for Neurodegenerative Disease Research, the Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA.The Department of Pathology and Laboratory Medicine, Institute on Aging and Center for Neurodegenerative Disease Research, the Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA.The Department of Pathology and Laboratory Medicine, Institute on Aging and Center for Neurodegenerative Disease Research, the Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA.The Department of Pathology and Laboratory Medicine, Institute on Aging and Center for Neurodegenerative Disease Research, the Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA.

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

33091110

Citation

Bassil, Fares, et al. "Α-Synuclein Modulates Tau Spreading in Mouse Brains." The Journal of Experimental Medicine, vol. 218, no. 1, 2021.
Bassil F, Meymand ES, Brown HJ, et al. Α-Synuclein modulates tau spreading in mouse brains. J Exp Med. 2021;218(1).
Bassil, F., Meymand, E. S., Brown, H. J., Xu, H., Cox, T. O., Pattabhiraman, S., Maghames, C. M., Wu, Q., Zhang, B., Trojanowski, J. Q., & Lee, V. M. (2021). Α-Synuclein modulates tau spreading in mouse brains. The Journal of Experimental Medicine, 218(1). https://doi.org/10.1084/jem.20192193
Bassil F, et al. Α-Synuclein Modulates Tau Spreading in Mouse Brains. J Exp Med. 2021 01 4;218(1) PubMed PMID: 33091110.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - α-Synuclein modulates tau spreading in mouse brains. AU - Bassil,Fares, AU - Meymand,Emily S, AU - Brown,Hannah J, AU - Xu,Hong, AU - Cox,Timothy O, AU - Pattabhiraman,Shankar, AU - Maghames,Chantal M, AU - Wu,Qihui, AU - Zhang,Bin, AU - Trojanowski,John Q, AU - Lee,Virginia M-Y, PY - 2019/11/20/received PY - 2020/03/12/revised PY - 2020/07/24/accepted PY - 2020/10/22/entrez PY - 2020/10/23/pubmed PY - 2021/8/31/medline JF - The Journal of experimental medicine JO - J Exp Med VL - 218 IS - 1 N2 - α-Synuclein (α-syn) and tau aggregates are the neuropathological hallmarks of Parkinson's disease (PD) and Alzheimer's disease (AD), respectively, although both pathologies co-occur in patients with these diseases, suggesting possible crosstalk between them. To elucidate the interactions of pathological α-syn and tau, we sought to model these interactions. We show that increased accumulation of tau aggregates occur following simultaneous introduction of α-syn mousepreformed fibrils (mpffs) and AD lysate-derived tau seeds (AD-tau) both in vitro and in vivo. Interestingly, the absence of endogenous mouse α-syn in mice reduces the accumulation and spreading of tau, while the absence of tau did not affect the seeding or spreading capacity of α-syn. These in vivo results are consistent with our in vitro data wherein the presence of tau has no synergistic effects on α-syn. Our results point to the important role of α-syn as a modulator of tau pathology burden and spreading in the brains of AD, PDD, and DLB patients. SN - 1540-9538 UR - https://www.unboundmedicine.com/medline/citation/33091110/��_Synuclein_modulates_tau_spreading_in_mouse_brains_ DB - PRIME DP - Unbound Medicine ER -