Extracellular vesicles contribute to the beneficial effects of exercise training in APP/PS1 mice

Oliver K. Fuller; Emma D. McLennan; Casey L. Egan; Nimna Perera; Lauren V. Terry; Jae Pyun; Mariana de Mendonca; Guilherme Defante Telles; Benoit Smeuninx; Emma L. Burrows; Ghizal Siddiqui; Darren J. Creek; John W. Scott; Michael A. Pearen; Pamali Fonseka; Joseph A. Nicolazzo; Suresh Mathivanan; Anthony J. Hannan; Grant A. Ramm; Martin Whitham; Mark A. Febbraio

doi:10.1016/j.isci.2025.111752

Extracellular vesicles contribute to the beneficial effects of exercise training in APP/PS1 mice

Oliver K. Fuller, Emma D. McLennan, Casey L. Egan, Nimna Perera, Lauren V. Terry, Jae Pyun, Mariana de Mendonca, Guilherme Defante Telles, Benoit Smeuninx, Emma L. Burrows, Ghizal Siddiqui, Darren J. Creek, John W. Scott, Michael A. Pearen, Pamali Fonseka, Joseph A. Nicolazzo, Suresh Mathivanan, Anthony J. Hannan, Grant A. Ramm, Martin WhithamMark A. Febbraio^*

^*Corresponding author for this work

Sport, Exercise and Rehabilitation Sciences

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Abstract

Exercise improves cognitive function in Alzheimer's disease (AD) via mechanism that are not fully clear. Here, we first examined the effect of voluntary exercise training (VET) on energy metabolism and cognitive function in the APP/PS1 transgenic mouse (Tg) model of familial AD. Next, we profiled extracellular vesicles (EVs) and examined whether they may play a role in the protective effects of VET via intranasal administration of EVs, purified from the blood of sedentary (sEV) and/or acutely exercised (eEV) donor wild-type mice into APP/PS1Tg mice. We show that VET reduced resting energy expenditure (REE) and improved cognition in APP/PS1 Tg mice. Administration of eEV, but not sEV, also reduced REE, but had no effect on cognition. Taken together, these data show that exercise is effective intervention to improve symptoms of AD in APP/PS1Tg mice. In addition, eEVs mediate some of these effects, implicating EVs in the treatment of age-related neurodegenerative diseases.

Original language	English
Article number	111752
Number of pages	23
Journal	iScience
Volume	28
Issue number	2
Early online date	4 Jan 2025
DOIs	https://doi.org/10.1016/j.isci.2025.111752
Publication status	Published - 21 Feb 2025

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Copyright:
© 2025 The Authors

Keywords

Cell biology
Molecular physiology
Neuroscience

ASJC Scopus subject areas

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Fuller, O. K., McLennan, E. D., Egan, C. L., Perera, N., Terry, L. V., Pyun, J., de Mendonca, M., Telles, G. D., Smeuninx, B., Burrows, E. L., Siddiqui, G., Creek, D. J., Scott, J. W., Pearen, M. A., Fonseka, P., Nicolazzo, J. A., Mathivanan, S., Hannan, A. J., Ramm, G. A., ... Febbraio, M. A. (2025). Extracellular vesicles contribute to the beneficial effects of exercise training in APP/PS1 mice. iScience, 28(2), Article 111752. https://doi.org/10.1016/j.isci.2025.111752

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title = "Extracellular vesicles contribute to the beneficial effects of exercise training in APP/PS1 mice",

abstract = "Exercise improves cognitive function in Alzheimer's disease (AD) via mechanism that are not fully clear. Here, we first examined the effect of voluntary exercise training (VET) on energy metabolism and cognitive function in the APP/PS1 transgenic mouse (Tg) model of familial AD. Next, we profiled extracellular vesicles (EVs) and examined whether they may play a role in the protective effects of VET via intranasal administration of EVs, purified from the blood of sedentary (sEV) and/or acutely exercised (eEV) donor wild-type mice into APP/PS1Tg mice. We show that VET reduced resting energy expenditure (REE) and improved cognition in APP/PS1 Tg mice. Administration of eEV, but not sEV, also reduced REE, but had no effect on cognition. Taken together, these data show that exercise is effective intervention to improve symptoms of AD in APP/PS1Tg mice. In addition, eEVs mediate some of these effects, implicating EVs in the treatment of age-related neurodegenerative diseases.",

keywords = "Cell biology, Molecular physiology, Neuroscience",

author = "Fuller, \{Oliver K.\} and McLennan, \{Emma D.\} and Egan, \{Casey L.\} and Nimna Perera and Terry, \{Lauren V.\} and Jae Pyun and \{de Mendonca\}, Mariana and Telles, \{Guilherme Defante\} and Benoit Smeuninx and Burrows, \{Emma L.\} and Ghizal Siddiqui and Creek, \{Darren J.\} and Scott, \{John W.\} and Pearen, \{Michael A.\} and Pamali Fonseka and Nicolazzo, \{Joseph A.\} and Suresh Mathivanan and Hannan, \{Anthony J.\} and Ramm, \{Grant A.\} and Martin Whitham and Febbraio, \{Mark A.\}",

note = "Copyright: {\textcopyright} 2025 The Authors",

year = "2025",

month = feb,

day = "21",

doi = "10.1016/j.isci.2025.111752",

language = "English",

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Fuller, OK, McLennan, ED, Egan, CL, Perera, N, Terry, LV, Pyun, J, de Mendonca, M, Telles, GD, Smeuninx, B, Burrows, EL, Siddiqui, G, Creek, DJ, Scott, JW, Pearen, MA, Fonseka, P, Nicolazzo, JA, Mathivanan, S, Hannan, AJ, Ramm, GA, Whitham, M & Febbraio, MA 2025, 'Extracellular vesicles contribute to the beneficial effects of exercise training in APP/PS1 mice', iScience, vol. 28, no. 2, 111752. https://doi.org/10.1016/j.isci.2025.111752

TY - JOUR

T1 - Extracellular vesicles contribute to the beneficial effects of exercise training in APP/PS1 mice

AU - Fuller, Oliver K.

AU - McLennan, Emma D.

AU - Egan, Casey L.

AU - Perera, Nimna

AU - Terry, Lauren V.

AU - Pyun, Jae

AU - de Mendonca, Mariana

AU - Telles, Guilherme Defante

AU - Smeuninx, Benoit

AU - Burrows, Emma L.

AU - Siddiqui, Ghizal

AU - Creek, Darren J.

AU - Scott, John W.

AU - Pearen, Michael A.

AU - Fonseka, Pamali

AU - Nicolazzo, Joseph A.

AU - Mathivanan, Suresh

AU - Hannan, Anthony J.

AU - Ramm, Grant A.

AU - Whitham, Martin

AU - Febbraio, Mark A.

PY - 2025/2/21

Y1 - 2025/2/21

N2 - Exercise improves cognitive function in Alzheimer's disease (AD) via mechanism that are not fully clear. Here, we first examined the effect of voluntary exercise training (VET) on energy metabolism and cognitive function in the APP/PS1 transgenic mouse (Tg) model of familial AD. Next, we profiled extracellular vesicles (EVs) and examined whether they may play a role in the protective effects of VET via intranasal administration of EVs, purified from the blood of sedentary (sEV) and/or acutely exercised (eEV) donor wild-type mice into APP/PS1Tg mice. We show that VET reduced resting energy expenditure (REE) and improved cognition in APP/PS1 Tg mice. Administration of eEV, but not sEV, also reduced REE, but had no effect on cognition. Taken together, these data show that exercise is effective intervention to improve symptoms of AD in APP/PS1Tg mice. In addition, eEVs mediate some of these effects, implicating EVs in the treatment of age-related neurodegenerative diseases.

AB - Exercise improves cognitive function in Alzheimer's disease (AD) via mechanism that are not fully clear. Here, we first examined the effect of voluntary exercise training (VET) on energy metabolism and cognitive function in the APP/PS1 transgenic mouse (Tg) model of familial AD. Next, we profiled extracellular vesicles (EVs) and examined whether they may play a role in the protective effects of VET via intranasal administration of EVs, purified from the blood of sedentary (sEV) and/or acutely exercised (eEV) donor wild-type mice into APP/PS1Tg mice. We show that VET reduced resting energy expenditure (REE) and improved cognition in APP/PS1 Tg mice. Administration of eEV, but not sEV, also reduced REE, but had no effect on cognition. Taken together, these data show that exercise is effective intervention to improve symptoms of AD in APP/PS1Tg mice. In addition, eEVs mediate some of these effects, implicating EVs in the treatment of age-related neurodegenerative diseases.

KW - Cell biology

KW - Molecular physiology

KW - Neuroscience

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U2 - 10.1016/j.isci.2025.111752

DO - 10.1016/j.isci.2025.111752

M3 - Article

AN - SCOPUS:85215112743

SN - 2589-0042

VL - 28

JO - iScience

JF - iScience

IS - 2

M1 - 111752

ER -

Extracellular vesicles contribute to the beneficial effects of exercise training in APP/PS1 mice

Abstract

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