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Striatal fibrinogen extravasation and vascular degeneration correlate with motor dysfunction in an aging mouse model of Alzheimer’s disease

Introduction: Alzheimer’s Disease (AD) patients exhibit signs of motor dysfunction, including gait, locomotion, and balance deficits. Changes in motor function often precede other symptoms of AD as well as correlate with increased severity and mortality. Despite the frequent occurrence of motor dysf...

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Autores principales: Berk-Rauch, Hanna E., Choudhury, Arnab, Richards, Allison T., Singh, Pradeep K., Chen, Zu-Lin, Norris, Erin H., Strickland, Sidney, Ahn, Hyung Jin
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10034037/
https://www.ncbi.nlm.nih.gov/pubmed/36967821
http://dx.doi.org/10.3389/fnagi.2023.1064178
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author Berk-Rauch, Hanna E.
Choudhury, Arnab
Richards, Allison T.
Singh, Pradeep K.
Chen, Zu-Lin
Norris, Erin H.
Strickland, Sidney
Ahn, Hyung Jin
author_facet Berk-Rauch, Hanna E.
Choudhury, Arnab
Richards, Allison T.
Singh, Pradeep K.
Chen, Zu-Lin
Norris, Erin H.
Strickland, Sidney
Ahn, Hyung Jin
author_sort Berk-Rauch, Hanna E.
collection PubMed
description Introduction: Alzheimer’s Disease (AD) patients exhibit signs of motor dysfunction, including gait, locomotion, and balance deficits. Changes in motor function often precede other symptoms of AD as well as correlate with increased severity and mortality. Despite the frequent occurrence of motor dysfunction in AD patients, little is known about the mechanisms by which this behavior is altered. Methods and Results: In the present study, we investigated the relationship between cerebrovascular impairment and motor dysfunction in a mouse model of AD (Tg6799). We found an age-dependent increase of extravasated fibrinogen deposits in the cortex and striatum of AD mice. Interestingly, there was significantly decreased cerebrovascular density in the striatum of the 15-month-old as compared to 7-month-old AD mice. We also found significant demyelination and axonal damage in the striatum of aged AD mice. We analyzed striatum-related motor function and anxiety levels of AD mice at both ages and found that aged AD mice exhibited significant impairment of motor function but not in the younger AD mice. Discussion: Our finding suggests an enticing correlation between extravasated fibrinogen, cerebrovascular damage of the striatum, and motor dysfunction in an AD mouse model, suggesting a possible mechanism underlying motor dysfunction in AD.
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spelling pubmed-100340372023-03-24 Striatal fibrinogen extravasation and vascular degeneration correlate with motor dysfunction in an aging mouse model of Alzheimer’s disease Berk-Rauch, Hanna E. Choudhury, Arnab Richards, Allison T. Singh, Pradeep K. Chen, Zu-Lin Norris, Erin H. Strickland, Sidney Ahn, Hyung Jin Front Aging Neurosci Aging Neuroscience Introduction: Alzheimer’s Disease (AD) patients exhibit signs of motor dysfunction, including gait, locomotion, and balance deficits. Changes in motor function often precede other symptoms of AD as well as correlate with increased severity and mortality. Despite the frequent occurrence of motor dysfunction in AD patients, little is known about the mechanisms by which this behavior is altered. Methods and Results: In the present study, we investigated the relationship between cerebrovascular impairment and motor dysfunction in a mouse model of AD (Tg6799). We found an age-dependent increase of extravasated fibrinogen deposits in the cortex and striatum of AD mice. Interestingly, there was significantly decreased cerebrovascular density in the striatum of the 15-month-old as compared to 7-month-old AD mice. We also found significant demyelination and axonal damage in the striatum of aged AD mice. We analyzed striatum-related motor function and anxiety levels of AD mice at both ages and found that aged AD mice exhibited significant impairment of motor function but not in the younger AD mice. Discussion: Our finding suggests an enticing correlation between extravasated fibrinogen, cerebrovascular damage of the striatum, and motor dysfunction in an AD mouse model, suggesting a possible mechanism underlying motor dysfunction in AD. Frontiers Media S.A. 2023-03-09 /pmc/articles/PMC10034037/ /pubmed/36967821 http://dx.doi.org/10.3389/fnagi.2023.1064178 Text en Copyright © 2023 Berk-Rauch, Choudhury, Richards, Singh, Chen, Norris, Strickland and Ahn. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Aging Neuroscience
Berk-Rauch, Hanna E.
Choudhury, Arnab
Richards, Allison T.
Singh, Pradeep K.
Chen, Zu-Lin
Norris, Erin H.
Strickland, Sidney
Ahn, Hyung Jin
Striatal fibrinogen extravasation and vascular degeneration correlate with motor dysfunction in an aging mouse model of Alzheimer’s disease
title Striatal fibrinogen extravasation and vascular degeneration correlate with motor dysfunction in an aging mouse model of Alzheimer’s disease
title_full Striatal fibrinogen extravasation and vascular degeneration correlate with motor dysfunction in an aging mouse model of Alzheimer’s disease
title_fullStr Striatal fibrinogen extravasation and vascular degeneration correlate with motor dysfunction in an aging mouse model of Alzheimer’s disease
title_full_unstemmed Striatal fibrinogen extravasation and vascular degeneration correlate with motor dysfunction in an aging mouse model of Alzheimer’s disease
title_short Striatal fibrinogen extravasation and vascular degeneration correlate with motor dysfunction in an aging mouse model of Alzheimer’s disease
title_sort striatal fibrinogen extravasation and vascular degeneration correlate with motor dysfunction in an aging mouse model of alzheimer’s disease
topic Aging Neuroscience
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10034037/
https://www.ncbi.nlm.nih.gov/pubmed/36967821
http://dx.doi.org/10.3389/fnagi.2023.1064178
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