Alzheimer's Imaging Consortium

Area of Science:

• Neuroscience
• Vascular Biology
• Metabolic Disorders

Background:

• Alzheimer's Disease (AD) pathology and vascular comorbidities interact, complicating human studies.
• Obesity is a prevalent vascular comorbidity increasing dementia risk, necessitating research in AD models.
• Translational imaging assays are needed to study AD and obesity interactions.

Purpose of the Study:

• To examine experimental Alzheimer's Disease (AD) models incorporating obesity.
• To establish sensitive and translational neuroimaging assays for AD and obesity.
• To investigate the impact of a high-carbohydrate, high-fat (HCHF) diet on neurovascular function in AD.

Main Methods:

• TgF344-AD (TgAD) rats and non-transgenic (nTg) littermates were fed a high-carbohydrate, high-fat (HCHF) diet for three months.
• Pseudo-continuous arterial spin labeling (pCASL) MRI was used to assess hippocampal neurovascular compromise.
• Functional hyperemia was measured in response to electrical forepaw stimulation at 12 months of age.

Main Results:

• CHOW-fed TgAD rats showed attenuated hippocampal functional hyperemia compared to nTg rats.
• HCHF diet enhanced functional hyperemia in TgAD rats, suggesting a rescue effect.
• The HCHF diet's effect on hyperemia differed between AD and normal aging models.

Conclusions:

• Metabolically dysregulated AD brains may benefit from calorie-dense food consumption, rescuing functional hyperemia.
• A non-invasive neuroimaging assay was developed to assess hippocampal neurovascular function in AD and comorbidities.
• The developed assay has high translational potential for patient studies due to ease of stimuli delivery and minimal confounding factors.