Reversal of high fat diet-induced obesity improves glucose tolerance, inflammatory response, ß-amyloid accumulation and cognitive decline in the APP/PSEN1 mouse model of Alzheimer's disease.
Neurobiol Dis
; 100: 87-98, 2017 Apr.
Article
in En
| MEDLINE
| ID: mdl-28108292
ABSTRACT
This study assessed the extent to which high fat diet (HFD)-induced ß-amyloid accumulation and cognitive decline in APP/PSEN1 mice are reversible through control of fat intake. Ten months of HFD (60% calories from fat) led to significant deficits in a 2-trial Y maze task, and nest building assay, and decreased voluntary locomotor activity. The HFD induced an inflammatory response, indicated by increased expression of several inflammatory markers. Substituting a low fat diet led to pronounced weight loss and correction of glucose intolerance, decreases in the inflammatory response, and improved performance on behavioral tasks in both wild-type and APP/PSEN1 transgenic mice. Insoluble ß-amyloid levels, and extent of tau phosphorylation were also lower following dietary reversal in APP/PSEN1 mice compared to high fat-fed animals, indicating that the inflammatory response may have contributed to key pathogenic pathways in the Alzheimer's disease model. The data suggest that weight loss can be a vital strategy for cognitive protection, but also highlight potential mechanisms for intervention when sustained weight loss is not possible.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Amyloid beta-Peptides
/
Presenilin-1
/
Alzheimer Disease
/
Cognitive Dysfunction
/
Diet, High-Fat
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Glucose
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Obesity
Limits:
Animals
Language:
En
Journal:
Neurobiol Dis
Journal subject:
NEUROLOGIA
Year:
2017
Type:
Article
Affiliation country:
United States