High fat diet worsens pathology and impairment in an Alzheimer’s mouse model, but not by synergistically decreasing cerebral blood flow
| Autor: | Mohammad Haft-Javaherian, Muse, Chris B. Schaffer, Brendah N. Njiru, Ramanauskaite Em, Pietro Michelucci, Madison Swallow, Nozomi Nishimura, Nancy E. Ruiz-Uribe, Muhammad Ali, Lindsay K. Vinarcsik, Kaja Falkenhain, Cruz Hernández Jc, Mohapatra A, Oliver Bracko |
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| Jazyk: | angličtina |
| Rok vydání: | 2019 |
| Předmět: |
0303 health sciences
Pathology medicine.medical_specialty business.industry Vascular inflammation Inflammation High fat diet Disease medicine.disease Obesity 03 medical and health sciences 0302 clinical medicine Cerebral blood flow nervous system mental disorders Medicine Alzheimer's disease medicine.symptom business Pathological 030217 neurology & neurosurgery 030304 developmental biology |
| DOI: | 10.1101/2019.12.16.878397 |
| Popis: | 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 showed that non-flowing capillaries, caused by adhered neutrophils, underlie the 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 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 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.Significance statementObesity, especially in mid-life, has been linked to increased risk for and severity of Alzheimer’s disease. Here, we show that blocking adhesion of white blood cells leads to increases in brain blood flow that improve cognitive function, regardless of whether mice are obese or not. |
| Databáze: | OpenAIRE |
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