Translational models for vascular cognitive impairment: a review including larger species

Atticus H Hainsworth; Stuart M Allan; Johannes Boltze; Catriona Cunningham; Chad Farris; Elizabeth Head; Masafumi Ihara; Jeremy D Isaacs; Raj N Kalaria; Saskia A M J Lesnik Oberstein; Mark B Moss; Björn Nitzsche; Gary A Rosenberg; Julie W Rutten; Melita Salkovic-Petrisic; Aron M Troen

doi:10.1186/s12916-017-0793-9

Translational models for vascular cognitive impairment: a review including larger species

Atticus H Hainsworth^* (Corresponding Author), Stuart M Allan, Johannes Boltze, Catriona Cunningham, Chad Farris, Elizabeth Head, Masafumi Ihara, Jeremy D Isaacs, Raj N Kalaria, Saskia A M J Lesnik Oberstein, Mark B Moss, Björn Nitzsche, Gary A Rosenberg, Julie W Rutten, Melita Salkovic-Petrisic, Aron M Troen

^*Corresponding author for this work

Research output: Contribution to journal › Review article › peer-review

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Abstract

BACKGROUND: Disease models are useful for prospective studies of pathology, identification of molecular and cellular mechanisms, pre-clinical testing of interventions, and validation of clinical biomarkers. Here, we review animal models relevant to vascular cognitive impairment (VCI). A synopsis of each model was initially presented by expert practitioners. Synopses were refined by the authors, and subsequently by the scientific committee of a recent conference (International Conference on Vascular Dementia 2015). Only peer-reviewed sources were cited.

METHODS: We included models that mimic VCI-related brain lesions (white matter hypoperfusion injury, focal ischaemia, cerebral amyloid angiopathy) or reproduce VCI risk factors (old age, hypertension, hyperhomocysteinemia, high-salt/high-fat diet) or reproduce genetic causes of VCI (CADASIL-causing Notch3 mutations).

CONCLUSIONS: We concluded that (1) translational models may reflect a VCI-relevant pathological process, while not fully replicating a human disease spectrum; (2) rodent models of VCI are limited by paucity of white matter; and (3) further translational models, and improved cognitive testing instruments, are required.

Original language	English
Article number	16
Number of pages	12
Journal	BMC medicine
Volume	15
Issue number	1
Early online date	25 Jan 2017
DOIs	https://doi.org/10.1186/s12916-017-0793-9
Publication status	Published - 2017

Bibliographical note

Acknowledgements
We are grateful to Professor Amos D Korczyn for his contributions to the VCI
field and for his helpful comments on this review.
Funding
AHH gratefully acknowledges funding from Alzheimer’s Drug Discovery
Foundation (ADDF grant no. 20140901), Alzheimer’s Society UK (PG146/151)
and Alzheimer’s Research UK (PPG2014A-8). SMA received research funding from the British Heart Foundation and EPSRC (UK). CC is funded by the
MRC (UK) Centre for Doctoral Training in Regenerative Medicine (grant no.
EP/L014904/1). AMT was supported in this work by Israel Science Foundation
(ISF) Grant 1353/11.

Keywords

Animals
Brain/pathology
Dementia, Vascular/genetics
Disease Models, Animal
Risk Factors

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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Cite this

Hainsworth, A. H., Allan, S. M., Boltze, J., Cunningham, C., Farris, C., Head, E., Ihara, M., Isaacs, J. D., Kalaria, R. N., Lesnik Oberstein, S. A. M. J., Moss, M. B., Nitzsche, B., Rosenberg, G. A., Rutten, J. W., Salkovic-Petrisic, M., & Troen, A. M. (2017). Translational models for vascular cognitive impairment: a review including larger species. BMC medicine , 15(1), [16]. https://doi.org/10.1186/s12916-017-0793-9

Hainsworth, AH, Allan, SM, Boltze, J, Cunningham, C, Farris, C, Head, E, Ihara, M, Isaacs, JD, Kalaria, RN, Lesnik Oberstein, SAMJ, Moss, MB, Nitzsche, B, Rosenberg, GA, Rutten, JW, Salkovic-Petrisic, M & Troen, AM 2017, 'Translational models for vascular cognitive impairment: a review including larger species', BMC medicine , vol. 15, no. 1, 16. https://doi.org/10.1186/s12916-017-0793-9

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title = "Translational models for vascular cognitive impairment: a review including larger species",

abstract = "BACKGROUND: Disease models are useful for prospective studies of pathology, identification of molecular and cellular mechanisms, pre-clinical testing of interventions, and validation of clinical biomarkers. Here, we review animal models relevant to vascular cognitive impairment (VCI). A synopsis of each model was initially presented by expert practitioners. Synopses were refined by the authors, and subsequently by the scientific committee of a recent conference (International Conference on Vascular Dementia 2015). Only peer-reviewed sources were cited.METHODS: We included models that mimic VCI-related brain lesions (white matter hypoperfusion injury, focal ischaemia, cerebral amyloid angiopathy) or reproduce VCI risk factors (old age, hypertension, hyperhomocysteinemia, high-salt/high-fat diet) or reproduce genetic causes of VCI (CADASIL-causing Notch3 mutations).CONCLUSIONS: We concluded that (1) translational models may reflect a VCI-relevant pathological process, while not fully replicating a human disease spectrum; (2) rodent models of VCI are limited by paucity of white matter; and (3) further translational models, and improved cognitive testing instruments, are required.",

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author = "Hainsworth, {Atticus H} and Allan, {Stuart M} and Johannes Boltze and Catriona Cunningham and Chad Farris and Elizabeth Head and Masafumi Ihara and Isaacs, {Jeremy D} and Kalaria, {Raj N} and {Lesnik Oberstein}, {Saskia A M J} and Moss, {Mark B} and Bj{\"o}rn Nitzsche and Rosenberg, {Gary A} and Rutten, {Julie W} and Melita Salkovic-Petrisic and Troen, {Aron M}",

note = "Acknowledgements We are grateful to Professor Amos D Korczyn for his contributions to the VCI field and for his helpful comments on this review. Funding AHH gratefully acknowledges funding from Alzheimer{\textquoteright}s Drug Discovery Foundation (ADDF grant no. 20140901), Alzheimer{\textquoteright}s Society UK (PG146/151) and Alzheimer{\textquoteright}s Research UK (PPG2014A-8). SMA received research funding from the British Heart Foundation and EPSRC (UK). CC is funded by the MRC (UK) Centre for Doctoral Training in Regenerative Medicine (grant no. EP/L014904/1). AMT was supported in this work by Israel Science Foundation (ISF) Grant 1353/11.",

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T2 - a review including larger species

AU - Hainsworth, Atticus H

AU - Allan, Stuart M

AU - Boltze, Johannes

AU - Cunningham, Catriona

AU - Farris, Chad

AU - Head, Elizabeth

AU - Ihara, Masafumi

AU - Isaacs, Jeremy D

AU - Kalaria, Raj N

AU - Lesnik Oberstein, Saskia A M J

AU - Moss, Mark B

AU - Nitzsche, Björn

AU - Rosenberg, Gary A

AU - Rutten, Julie W

AU - Salkovic-Petrisic, Melita

AU - Troen, Aron M

N1 - Acknowledgements We are grateful to Professor Amos D Korczyn for his contributions to the VCI field and for his helpful comments on this review. Funding AHH gratefully acknowledges funding from Alzheimer’s Drug Discovery Foundation (ADDF grant no. 20140901), Alzheimer’s Society UK (PG146/151) and Alzheimer’s Research UK (PPG2014A-8). SMA received research funding from the British Heart Foundation and EPSRC (UK). CC is funded by the MRC (UK) Centre for Doctoral Training in Regenerative Medicine (grant no. EP/L014904/1). AMT was supported in this work by Israel Science Foundation (ISF) Grant 1353/11.

PY - 2017

Y1 - 2017

N2 - BACKGROUND: Disease models are useful for prospective studies of pathology, identification of molecular and cellular mechanisms, pre-clinical testing of interventions, and validation of clinical biomarkers. Here, we review animal models relevant to vascular cognitive impairment (VCI). A synopsis of each model was initially presented by expert practitioners. Synopses were refined by the authors, and subsequently by the scientific committee of a recent conference (International Conference on Vascular Dementia 2015). Only peer-reviewed sources were cited.METHODS: We included models that mimic VCI-related brain lesions (white matter hypoperfusion injury, focal ischaemia, cerebral amyloid angiopathy) or reproduce VCI risk factors (old age, hypertension, hyperhomocysteinemia, high-salt/high-fat diet) or reproduce genetic causes of VCI (CADASIL-causing Notch3 mutations).CONCLUSIONS: We concluded that (1) translational models may reflect a VCI-relevant pathological process, while not fully replicating a human disease spectrum; (2) rodent models of VCI are limited by paucity of white matter; and (3) further translational models, and improved cognitive testing instruments, are required.

AB - BACKGROUND: Disease models are useful for prospective studies of pathology, identification of molecular and cellular mechanisms, pre-clinical testing of interventions, and validation of clinical biomarkers. Here, we review animal models relevant to vascular cognitive impairment (VCI). A synopsis of each model was initially presented by expert practitioners. Synopses were refined by the authors, and subsequently by the scientific committee of a recent conference (International Conference on Vascular Dementia 2015). Only peer-reviewed sources were cited.METHODS: We included models that mimic VCI-related brain lesions (white matter hypoperfusion injury, focal ischaemia, cerebral amyloid angiopathy) or reproduce VCI risk factors (old age, hypertension, hyperhomocysteinemia, high-salt/high-fat diet) or reproduce genetic causes of VCI (CADASIL-causing Notch3 mutations).CONCLUSIONS: We concluded that (1) translational models may reflect a VCI-relevant pathological process, while not fully replicating a human disease spectrum; (2) rodent models of VCI are limited by paucity of white matter; and (3) further translational models, and improved cognitive testing instruments, are required.

KW - Animals

KW - Brain/pathology

KW - Dementia, Vascular/genetics

KW - Disease Models, Animal

KW - Risk Factors

U2 - 10.1186/s12916-017-0793-9

DO - 10.1186/s12916-017-0793-9

M3 - Review article

C2 - 28118831

SN - 1741-7015

VL - 15

JO - BMC medicine

JF - BMC medicine

IS - 1

M1 - 16

ER -

Translational models for vascular cognitive impairment: a review including larger species

Abstract

Bibliographical note

Keywords

UN SDGs

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