P4‐076: Non‐transgenic Dietary‐induced Models of Ad‐like Pathology and Dementia in the Rabbit
Year: 2019
Type: article
Abstract: Diabetes and high cholesterol are risk factors for acquiring Alzheimer's Disease (AD). The purpose of this study is to develop a diet-based, non-transgenic animal model of sporadic AD. The rabbit was selected because its amino acid sequence for amyloid is nearly identical to the human sequence, its lipid metabolism is very similar to that of humans, and it can be imaged without sedation. Intrinsic connectivity and memory of young adult rabbits was assayed with fMRI and novel object/novel place recognition prior to starting one of 3 diets (high fat/high sugar, high cholesterol, normal chow). Memory and blood chemistry were assayed on a monthly basis; functional connectivity was assayed once again near the end of the experiment (after being on diet for approximately five months). The brain was then assayed for tau and soluble amyloid with immunohistochemistry of hippocampal and frontal cortex brain slices. The cholesterol diet induced hypercholesterolemia (>1000mg/dl) and the fat/fructose diet induced a state of type two diabetes (BGL> 126 mg/dl). Both experimental diets induced memory impairments on hippocampal-dependent place recognition. Results of eyeblink conditioning (EBC) and immunohistochemistry (IHC) are being collected, but pilot data from rabbits on the cholesterol diet indicated impaired acquisition of EBC and increased staining for soluble amyloid oligomer and hyperphosphorylated tau. Dietary induced metabolic disturbances in the rabbit can be used to examine mechanisms and treatments for effects of Type 2 diabetes and hypercholesterolemia that promote AD-like cognitive deficits and neuronal pathology.
Source: Alzheimer s & Dementia
Institution: Northwestern University
Language: English
Subfield: Physiology
Field: Medicine
Domain: Health Sciences
Open Access status: bronze
OpenAlex ID: W2981019781