title: Chronic consumption of a western diet induces robust glial activation in aging mice and in a mouse model of Alzheimer's disease.
abstract: Studies have assessed individual components of a western diet, but no study has assessed the long-term, cumulative effects of a western diet on aging and Alzheimer's disease (AD). Therefore, we have formulated the first western-style diet that mimics the fat, carbohydrate, protein, vitamin and mineral levels of western diets. This diet was fed to aging C57BL/6J (B6) mice to identify phenotypes that may increase susceptibility to AD, and to APP/PS1 mice, a mouse model of AD, to determine the effects of the diet in AD. Astrocytosis and microglia/monocyte activation were dramatically increased in response to diet and was further increased in APP/PS1 mice fed the western diet. This increase in glial responses was associated with increased plaque burden in the hippocampus. Interestingly, given recent studies highlighting the importance of TREM2 in microglia/monocytes in AD susceptibility and progression, B6 and APP/PS1 mice fed the western diet showed significant increases TREM2+ microglia/monocytes. Therefore, an increase in TREM2+ microglia/monocytes may underlie the increased risk from a western diet to age-related neurodegenerative diseases such as Alzheimer's disease. This study lays the foundation to fully investigate the impact of a western diet on glial responses in aging and Alzheimer's disease.
authors.affiliation: The Jackson Laboratory, 600 Main St, Bar Harbor, ME, USA.|Graduate Program in Genetics, Sackler School of Graduate Biomedical Sciences, Tufts University, 136 Harrison Avenue, Boston, MA 02111, USA.
authors.forename: Leah C
authors.initials: LC
authors.lastname: Graham
authors.affiliation: The Jackson Laboratory, 600 Main St, Bar Harbor, ME, USA.
authors.forename: Jeffrey M
authors.initials: JM
authors.lastname: Harder
authors.affiliation: The Jackson Laboratory, 600 Main St, Bar Harbor, ME, USA.
authors.forename: Ileana
authors.initials: I
authors.lastname: Soto
authors.affiliation: The Jackson Laboratory, 600 Main St, Bar Harbor, ME, USA.|Howard Hughes Medical Institute, 600 Main St, Bar Harbor, ME, USA.
authors.forename: Wilhelmine N
authors.initials: WN
authors.lastname: de Vries
authors.affiliation: The Jackson Laboratory, 600 Main St, Bar Harbor, ME, USA.|Graduate Program in Genetics, Sackler School of Graduate Biomedical Sciences, Tufts University, 136 Harrison Avenue, Boston, MA 02111, USA.|Howard Hughes Medical Institute, 600 Main St, Bar Harbor, ME, USA.|Department of Ophthalmology, Tufts University School of Medicine, Boston, MA, USA.
authors.forename: Simon W M
authors.initials: SW
authors.lastname: John
authors.affiliation: The Jackson Laboratory, 600 Main St, Bar Harbor, ME, USA.|Graduate Program in Genetics, Sackler School of Graduate Biomedical Sciences, Tufts University, 136 Harrison Avenue, Boston, MA 02111, USA.
authors.forename: Gareth R
authors.initials: GR
authors.lastname: Howell
mesh_terms: D000375:Aging / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D000544:Alzheimer Disease / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D000818:Animals; D066273:Diet, Western / Q000009:adverse effects*; D004195:Disease Models, Animal; D005911:Gliosis / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D051379:Mice; D008822:Mice, Transgenic; D017628:Microglia / Q000378:metabolism* / Q000473:pathology