Regional vulnerability and spreading of hyperphosphorylated tau in seeded mouse brain

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Regional vulnerability and spreading of hyperphosphorylated tau in seeded mouse brain. / Detrez, Jan R.; Maurin, Hervé ; Van Kolen, Kristof; Willems, Roland; Colombelli, Julien; Lechat, Benoit; Roucourt, Bart; Van Leuven, Fred; Baatout, Sarah; Larsen, Peter; Nuydens, Rony; Timmermans, Jean-Pierre; De Vos, Winnok H.

In: Neurobiology of Disease, Vol. 127, 14.03.2019, p. 398-409.

Research output: Contribution to journalArticlepeer-review

Harvard

Detrez, JR, Maurin, H, Van Kolen, K, Willems, R, Colombelli, J, Lechat, B, Roucourt, B, Van Leuven, F, Baatout, S, Larsen, P, Nuydens, R, Timmermans, J-P & De Vos, WH 2019, 'Regional vulnerability and spreading of hyperphosphorylated tau in seeded mouse brain', Neurobiology of Disease, vol. 127, pp. 398-409. https://doi.org/10.1016/j.nbd.2019.03.010

APA

Detrez, J. R., Maurin, H., Van Kolen, K., Willems, R., Colombelli, J., Lechat, B., Roucourt, B., Van Leuven, F., Baatout, S., Larsen, P., Nuydens, R., Timmermans, J-P., & De Vos, W. H. (2019). Regional vulnerability and spreading of hyperphosphorylated tau in seeded mouse brain. Neurobiology of Disease, 127, 398-409. https://doi.org/10.1016/j.nbd.2019.03.010

Vancouver

Detrez JR, Maurin H, Van Kolen K, Willems R, Colombelli J, Lechat B et al. Regional vulnerability and spreading of hyperphosphorylated tau in seeded mouse brain. Neurobiology of Disease. 2019 Mar 14;127:398-409. https://doi.org/10.1016/j.nbd.2019.03.010

Author

Detrez, Jan R. ; Maurin, Hervé ; Van Kolen, Kristof ; Willems, Roland ; Colombelli, Julien ; Lechat, Benoit ; Roucourt, Bart ; Van Leuven, Fred ; Baatout, Sarah ; Larsen, Peter ; Nuydens, Rony ; Timmermans, Jean-Pierre ; De Vos, Winnok H. / Regional vulnerability and spreading of hyperphosphorylated tau in seeded mouse brain. In: Neurobiology of Disease. 2019 ; Vol. 127. pp. 398-409.

Bibtex - Download

@article{2f1371ac02af4139965ad974c845d11a,
title = "Regional vulnerability and spreading of hyperphosphorylated tau in seeded mouse brain",
abstract = "We have exploited whole brain microscopy to map the progressive deposition of hyperphosphorylated tau in intact, cleared mouse brain. We found that the three-dimensional spreading pattern of hyperphosphorylated tau in the brain of an aging Tau.P301L mouse model did not resemble that observed in AD patients. Injection of synthetic or patient-derived tau fibrils in the CA1 region resulted in a more faithful spreading pattern. Atlasguided volumetric analysis showed a connectome-dependent spreading from the injection site and also revealed hyperphosphorylated tau deposits beyond the direct anatomical connections. In fibril-injected brains, we also detected a persistent subpopulation of rod-like and swollen microglia. Furthermore, we showed that the hyperphosphorylated tau load could be reduced by intracranial co-administration of, and to a lesser extent, by repeated systemic dosing with an antibody targeting the microtubule-binding domain of tau. Thus, the combination of targeted seeding and in toto staging of tau pathology allowed assessing regional vulnerability in a comprehensive manner, and holds potential as a preclinical drug validation tool",
keywords = "Hyperphosphorylated tau, Tau, Alzheimer's disease, Tau.P301L, Whole brain imaging, Light-sheet microscopy, Tissue clearing, Microglia",
author = "Detrez, {Jan R.} and Herv{\'e} Maurin and {Van Kolen}, Kristof and Roland Willems and Julien Colombelli and Benoit Lechat and Bart Roucourt and {Van Leuven}, Fred and Sarah Baatout and Peter Larsen and Rony Nuydens and Jean-Pierre Timmermans and {De Vos}, {Winnok H.}",
note = "Score=10",
year = "2019",
month = mar,
day = "14",
doi = "10.1016/j.nbd.2019.03.010",
language = "English",
volume = "127",
pages = "398--409",
journal = "Neurobiology of Disease",
issn = "0969-9961",
publisher = "Elsevier",

}

RIS - Download

TY - JOUR

T1 - Regional vulnerability and spreading of hyperphosphorylated tau in seeded mouse brain

AU - Detrez, Jan R.

AU - Maurin, Hervé

AU - Van Kolen, Kristof

AU - Willems, Roland

AU - Colombelli, Julien

AU - Lechat, Benoit

AU - Roucourt, Bart

AU - Van Leuven, Fred

AU - Baatout, Sarah

AU - Larsen, Peter

AU - Nuydens, Rony

AU - Timmermans, Jean-Pierre

AU - De Vos, Winnok H.

N1 - Score=10

PY - 2019/3/14

Y1 - 2019/3/14

N2 - We have exploited whole brain microscopy to map the progressive deposition of hyperphosphorylated tau in intact, cleared mouse brain. We found that the three-dimensional spreading pattern of hyperphosphorylated tau in the brain of an aging Tau.P301L mouse model did not resemble that observed in AD patients. Injection of synthetic or patient-derived tau fibrils in the CA1 region resulted in a more faithful spreading pattern. Atlasguided volumetric analysis showed a connectome-dependent spreading from the injection site and also revealed hyperphosphorylated tau deposits beyond the direct anatomical connections. In fibril-injected brains, we also detected a persistent subpopulation of rod-like and swollen microglia. Furthermore, we showed that the hyperphosphorylated tau load could be reduced by intracranial co-administration of, and to a lesser extent, by repeated systemic dosing with an antibody targeting the microtubule-binding domain of tau. Thus, the combination of targeted seeding and in toto staging of tau pathology allowed assessing regional vulnerability in a comprehensive manner, and holds potential as a preclinical drug validation tool

AB - We have exploited whole brain microscopy to map the progressive deposition of hyperphosphorylated tau in intact, cleared mouse brain. We found that the three-dimensional spreading pattern of hyperphosphorylated tau in the brain of an aging Tau.P301L mouse model did not resemble that observed in AD patients. Injection of synthetic or patient-derived tau fibrils in the CA1 region resulted in a more faithful spreading pattern. Atlasguided volumetric analysis showed a connectome-dependent spreading from the injection site and also revealed hyperphosphorylated tau deposits beyond the direct anatomical connections. In fibril-injected brains, we also detected a persistent subpopulation of rod-like and swollen microglia. Furthermore, we showed that the hyperphosphorylated tau load could be reduced by intracranial co-administration of, and to a lesser extent, by repeated systemic dosing with an antibody targeting the microtubule-binding domain of tau. Thus, the combination of targeted seeding and in toto staging of tau pathology allowed assessing regional vulnerability in a comprehensive manner, and holds potential as a preclinical drug validation tool

KW - Hyperphosphorylated tau

KW - Tau

KW - Alzheimer's disease

KW - Tau.P301L

KW - Whole brain imaging

KW - Light-sheet microscopy

KW - Tissue clearing

KW - Microglia

UR - http://ecm.sckcen.be/OTCS/llisapi.dll/open/33502975

U2 - 10.1016/j.nbd.2019.03.010

DO - 10.1016/j.nbd.2019.03.010

M3 - Article

VL - 127

SP - 398

EP - 409

JO - Neurobiology of Disease

JF - Neurobiology of Disease

SN - 0969-9961

ER -

ID: 5034883