# Interruption of the Gut Integrity Contributes to Early Accumulation of Amyloid-β in the Enteric Nervous System in Rats Supplemented with a High-Fat Diet

## TL;DR

A high-fat diet in rats leads to early amyloid buildup in gut nerves and memory issues before brain damage occurs.

## Contribution

Shows early amyloid-β accumulation in the gut nervous system precedes brain involvement with high-fat diets.

## Key findings

- High-fat diet caused memory deficits and amyloid-β in gut nerves after 4-8 weeks.
- Amyloid-β deposition in the myenteric plexus occurred before cerebral cortex involvement.
- Longer high-fat diet duration worsened spatial memory and gut mucosa damage.

## Abstract

Consumption of a high-fat diet (HFD) contributes to numerous chronic illnesses, including neurological disorders and gastrointestinal dysfunction. The study design included four groups, each consisting of six rats: the control group was fed regular chow, while groups 2 (HFD 2W), 3 (HFD 4W), and 4 (HFD 8W) were given a 60% HFD for 2, 4, and 8 weeks, respectively. A significant change in the latency to the platform in the water maze, a decrease in the percentage of successful cycles in the Y-maze, and a reduction in the percentage of time spent with the novel object were observed between the baseline and endpoint results in the HFD 4W and HFD 8W groups; notably, this was not the case in the control and HFD 2W groups. Consistent with the increased duration of HFD intake, marked damage to the cortical pyramidal cells as well as the mucosa of the ileum and colon was recorded. The optical density of amyloid deposition was significantly increased in the myenteric plexus before the cerebral cortex. In conclusion, increasing the duration of 60% HFD consumption was associated with significant deterioration of spatial and working memory, an increase in lipid profile, and amyloid deposition in the enteric nervous system, which began even before the observable involvement of the cerebral cortex.

The online version contains supplementary material available at 10.1007/s12035-025-05261-1.