Abstract
Obesity, a known risk factor of Alzheimer’s disease (AD), increases the activation of microglia, leading to a proinflammatory phenotype. Our previous work shows that a high fat diet (HFD) can cause neuroinflammation and cognitive decline in mice. We hypothesized that proinflammatory activation of brain microglia in obesity exacerbates AD pathology and increases the accumulation of amyloid beta (Aβ) plaques. Presently, we tested cognitive function in 8-month-old male and female APP/PS1 mice fed a HFD, starting at 1.5 months of age. Locomotor activity, anxiety-like behavior, behavioral despair, and spatial memory were all assessed through behavioral tests. Microgliosis and Aβ deposition were measured in multiple brain regions through immunohistochemical analysis. Our results show that a HFD decreases locomotor activity, while increasing anxiety-like behavior and behavioral despair independent of genotype. A HFD led to increased memory deficits in both sexes, with HFD-fed APP/PS1 mice performing the worst out of all groups. Immunohistochemical analysis showed increased microgliosis in mice fed a HFD. This was accompanied by an increase in Aβ deposition in the HFD-fed APP/PS1 mice. Together, our results support that HFD-induced obesity exacerbates neuroinflammation and Aβ deposition in a young adult AD mouse model, leading to increased memory deficits and cognitive decline in both sexes.
Original language | English (US) |
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Article number | 2494 |
Journal | Nutrients |
Volume | 15 |
Issue number | 11 |
DOIs | |
State | Published - Jun 2023 |
Bibliographical note
Funding Information:This research was funded by the U.S. Department of Veterans Affairs grant I01 BX004146 to T.A.B., Alzheimer’s Association grant AARGD-17-505409 to T.A.B. and J.P.N., and the UMN Healthy Foods, Healthy Lives Institute Planning Grant Program to T.A.B. and J.P.N.
Publisher Copyright:
© 2023 by the authors.
Keywords
- Alzheimer’s disease
- amyloid beta
- cognitive decline
- inflammation
- obesity
PubMed: MeSH publication types
- Journal Article