High Fat Diet Aggravates AD-Related Pathogenic Processes in APP/PS1 Mice

Area of Science:

• Neuroscience
• Metabolic Disorders
• Aging Research

Background:

• Alzheimer's disease (AD) is a leading neurodegenerative disorder.
• Negative lifestyle factors, including high-fat diets (HFD), are implicated in AD pathogenesis.
• Insulin resistance (IR), often linked to HFD, is associated with increased risk of AD and amyloidogenesis.

Purpose of the Study:

• To investigate the impact of HFD on amyloidogenesis and cognitive deficits in AD model mice.
• To clarify the role of HFD-induced insulin resistance in Alzheimer's disease progression.

Main Methods:

• APP/PS1 mice, an established model for AD, were fed an HFD for four months.
• Evaluated insulin resistance in peripheral tissues and the brain.
• Assessed cognitive function, dendritic integrity, and synaptic protein expression.
• Measured the expression of BACE1 and IDE, key enzymes in amyloid-beta processing.

Main Results:

• HFD feeding increased insulin resistance in both the periphery and brain of APP/PS1 mice.
• Long-term HFD exacerbated cognitive deficits and impaired synaptic integrity.
• HFD led to increased BACE1 and decreased IDE expression, promoting beta-amyloid accumulation.

Conclusions:

• Long-term HFD, coupled with insulin resistance, promotes beta-amyloid toxicity and cognitive decline in AD models.
• Modifiable lifestyle factors, such as HFD-induced IR, may significantly contribute to Alzheimer's disease pathogenesis.
• These findings highlight the critical link between diet, metabolic health, and neurodegeneration.