High fat diet worsens Alzheimer’s disease-related behavioral abnormalities and neuropathology in APP/PS1 mice, but not by synergistically decreasing cerebral blood flow

Abstract Obesity is linked to increased risk for and severity of Alzheimer’s disease (AD). Cerebral blood flow (CBF) reductions are an early feature of AD and are also linked to obesity. We recently showed that non-flowing capillaries, caused by adhered neutrophils, contribute to CBF reduction in mo...

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Autores principales:	Oliver Bracko, Lindsay K. Vinarcsik, Jean C. Cruz Hernández, Nancy E. Ruiz-Uribe, Mohammad Haft-Javaherian, Kaja Falkenhain, Egle M. Ramanauskaite, Muhammad Ali, Aditi Mohapatra, Madisen A. Swallow, Brendah N. Njiru, Victorine Muse, Pietro E. Michelucci, Nozomi Nishimura, Chris B. Schaffer
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2020
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/e9f076f1a1ac4a1ca9d345e6325e1739
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spelling	oai:doaj.org-article:e9f076f1a1ac4a1ca9d345e6325e17392021-12-02T17:41:07ZHigh fat diet worsens Alzheimer’s disease-related behavioral abnormalities and neuropathology in APP/PS1 mice, but not by synergistically decreasing cerebral blood flow10.1038/s41598-020-65908-y2045-2322https://doaj.org/article/e9f076f1a1ac4a1ca9d345e6325e17392020-06-01T00:00:00Zhttps://doi.org/10.1038/s41598-020-65908-yhttps://doaj.org/toc/2045-2322Abstract Obesity is linked to increased risk for and severity of Alzheimer’s disease (AD). Cerebral blood flow (CBF) reductions are an early feature of AD and are also linked to obesity. We recently showed that non-flowing capillaries, caused by adhered neutrophils, contribute to CBF reduction in mouse models of AD. Because obesity could exacerbate the vascular inflammation likely underlying this neutrophil adhesion, we tested links between obesity and AD by feeding APP/PS1 mice a high fat diet (Hfd) and evaluating behavioral, physiological, and pathological changes. We found trends toward poorer memory performance in APP/PS1 mice fed a Hfd, impaired social interactions with either APP/PS1 genotype or a Hfd, and synergistic impairment of sensory-motor function in APP/PS1 mice fed a Hfd. The Hfd led to increases in amyloid-beta monomers and plaques in APP/PS1 mice, as well as increased brain inflammation. These results agree with previous reports showing obesity exacerbates AD-related pathology and symptoms in mice. We used a crowd-sourced, citizen science approach to analyze imaging data to determine the impact of the APP/PS1 genotype and a Hfd on capillary stalling and CBF. Surprisingly, we did not see an increase in the number of non-flowing capillaries or a worsening of the CBF deficit in APP/PS1 mice fed a Hfd as compared to controls, suggesting that capillary stalling is not a mechanistic link between a Hfd and increased severity of AD in mice. Reducing capillary stalling by blocking neutrophil adhesion improved CBF and short-term memory function in APP/PS1 mice, even when fed a Hfd.Oliver BrackoLindsay K. VinarcsikJean C. Cruz HernándezNancy E. Ruiz-UribeMohammad Haft-JavaherianKaja FalkenhainEgle M. RamanauskaiteMuhammad AliAditi MohapatraMadisen A. SwallowBrendah N. NjiruVictorine MusePietro E. MichelucciNozomi NishimuraChris B. SchafferNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 10, Iss 1, Pp 1-16 (2020)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Oliver Bracko Lindsay K. Vinarcsik Jean C. Cruz Hernández Nancy E. Ruiz-Uribe Mohammad Haft-Javaherian Kaja Falkenhain Egle M. Ramanauskaite Muhammad Ali Aditi Mohapatra Madisen A. Swallow Brendah N. Njiru Victorine Muse Pietro E. Michelucci Nozomi Nishimura Chris B. Schaffer High fat diet worsens Alzheimer’s disease-related behavioral abnormalities and neuropathology in APP/PS1 mice, but not by synergistically decreasing cerebral blood flow
description	Abstract Obesity is linked to increased risk for and severity of Alzheimer’s disease (AD). Cerebral blood flow (CBF) reductions are an early feature of AD and are also linked to obesity. We recently showed that non-flowing capillaries, caused by adhered neutrophils, contribute to CBF reduction in mouse models of AD. Because obesity could exacerbate the vascular inflammation likely underlying this neutrophil adhesion, we tested links between obesity and AD by feeding APP/PS1 mice a high fat diet (Hfd) and evaluating behavioral, physiological, and pathological changes. We found trends toward poorer memory performance in APP/PS1 mice fed a Hfd, impaired social interactions with either APP/PS1 genotype or a Hfd, and synergistic impairment of sensory-motor function in APP/PS1 mice fed a Hfd. The Hfd led to increases in amyloid-beta monomers and plaques in APP/PS1 mice, as well as increased brain inflammation. These results agree with previous reports showing obesity exacerbates AD-related pathology and symptoms in mice. We used a crowd-sourced, citizen science approach to analyze imaging data to determine the impact of the APP/PS1 genotype and a Hfd on capillary stalling and CBF. Surprisingly, we did not see an increase in the number of non-flowing capillaries or a worsening of the CBF deficit in APP/PS1 mice fed a Hfd as compared to controls, suggesting that capillary stalling is not a mechanistic link between a Hfd and increased severity of AD in mice. Reducing capillary stalling by blocking neutrophil adhesion improved CBF and short-term memory function in APP/PS1 mice, even when fed a Hfd.
format	article
author	Oliver Bracko Lindsay K. Vinarcsik Jean C. Cruz Hernández Nancy E. Ruiz-Uribe Mohammad Haft-Javaherian Kaja Falkenhain Egle M. Ramanauskaite Muhammad Ali Aditi Mohapatra Madisen A. Swallow Brendah N. Njiru Victorine Muse Pietro E. Michelucci Nozomi Nishimura Chris B. Schaffer
author_facet	Oliver Bracko Lindsay K. Vinarcsik Jean C. Cruz Hernández Nancy E. Ruiz-Uribe Mohammad Haft-Javaherian Kaja Falkenhain Egle M. Ramanauskaite Muhammad Ali Aditi Mohapatra Madisen A. Swallow Brendah N. Njiru Victorine Muse Pietro E. Michelucci Nozomi Nishimura Chris B. Schaffer
author_sort	Oliver Bracko
title	High fat diet worsens Alzheimer’s disease-related behavioral abnormalities and neuropathology in APP/PS1 mice, but not by synergistically decreasing cerebral blood flow
title_short	High fat diet worsens Alzheimer’s disease-related behavioral abnormalities and neuropathology in APP/PS1 mice, but not by synergistically decreasing cerebral blood flow
title_full	High fat diet worsens Alzheimer’s disease-related behavioral abnormalities and neuropathology in APP/PS1 mice, but not by synergistically decreasing cerebral blood flow
title_fullStr	High fat diet worsens Alzheimer’s disease-related behavioral abnormalities and neuropathology in APP/PS1 mice, but not by synergistically decreasing cerebral blood flow
title_full_unstemmed	High fat diet worsens Alzheimer’s disease-related behavioral abnormalities and neuropathology in APP/PS1 mice, but not by synergistically decreasing cerebral blood flow
title_sort	high fat diet worsens alzheimer’s disease-related behavioral abnormalities and neuropathology in app/ps1 mice, but not by synergistically decreasing cerebral blood flow
publisher	Nature Portfolio
publishDate	2020
url	https://doaj.org/article/e9f076f1a1ac4a1ca9d345e6325e1739
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High fat diet worsens Alzheimer’s disease-related behavioral abnormalities and neuropathology in APP/PS1 mice, but not by synergistically decreasing cerebral blood flow

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