High fat diet exacerbates Alzheimer's disease-related pathology in APPswe/PS1 mice
Bibliographic record
Abstract
// Peter Thériault 1 , Ayman ElAli 2 and Serge Rivest 1 1 Neuroscience Laboratory, CHU de Québec Research Center and Department of Molecular Medicine, Faculty of Medicine, Laval University, Québec City, QC, Canada 2 Neuroscience Laboratory, CHU de Québec Research Center and Department of Psychiatry and Neuroscience, Faculty of Medicine, Laval University, Québec City, QC, Canada Correspondence to: Serge Rivest, email: // Keywords : Alzheimer’s disease; age; high fat diet; blood-brain barrier; pericyte; Pathology Section Received : June 11, 2016 Accepted : September 16, 2016 Published : September 21, 2016 Abstract Alzheimer’s disease (AD) is mainly characterized by the accumulation and aggregation of amyloid-β (Aβ) peptides in brain parenchyma and cerebral microvasculature. Unfortunately, the exact causes of the disease are still unclear. However, blood-brain barrier (BBB) dysfunction and activation of inflammatory pathways are implicated in AD pathogenesis. Importantly, advanced age and high fat diet, two major risk factors associated with AD, were shown to deeply affect BBB function and modulate the immune response. As such, this study evaluated the impact of age and high fat diet on AD progression. For this purpose, 3 (i.e. young) and 12 (i.e. aged) months old APPswe/PS1 mice were fed for 4 months with a high fat diet (i.e. Western diet (WD)) or normal diet. Interestingly, neurobehavioral tests revealed that WD accelerates age-associated cognitive decline without affecting parenchymal Aβ. Nonetheless, WD decreases matrix metalloproteinase-9 enzymatic activity and brain-derived neurotrophic factor mRNA and protein levels in brain, suggesting loss of synaptic plasticity. In the periphery, WD promotes systemic inflammation by increasing the levels of blood-circulating monocytes and monocyte chemotactic protein-1 production, which is accompanied by an augmentation of oxidized-low density lipoprotein levels in blood circulation. At the BBB, WD potentiates the age-induced increase of Aβ 1-40 accumulation and exacerbates the oxidative stress, specifically in cerebral microvasculature. These effects were accompanied by the dysfunction of pericytes, thus altering BBB functionality without compromising its integrity. Our study provides new insights into the implication of high fat diet in accelerating the cognitive decline in AD.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.001 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.001 | 0.002 |
| Insufficient payload (model declined to judge) | 0.002 | 0.001 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".