Work

A high cholesterol diet accelerates Alzheimer's progression by promoting fibrotic damage in rats

Year: 2025

Type: article

Abstract: • Oxysterols and TGFβ can cause fibrotic damage in the brain. • High-cholesterol diet in rats led to increased oxysterols, TGFβ, Aβ, and MMP-9 and decreased Claudin-5, ABCA1, HDL, and antioxidant regulations in rats. • Oxysterol buildup may result in Aβ accumulation due to TGFβ hyperactivation. • The study explores the role of oxysterols in Alzheimer's disease pathogenesis. • Uncovering mechanisms of oxysterols and fibrotic mediators may lead to novel therapies. The literature documents the ability of oxysterols and TGFβ to cause fibrotic damage in the brain. Our study explores the potential mechanisms of oxysterol interactions with fibrotic mediators in Alzheimer's disease. It focuses on peripherally formed oxysterols and their effects on TGFβ hyperactivation in an experimental rodent model of Alzheimer's disease. We fed experimental rats a high-cholesterol diet for eight weeks and evaluated their cognitive abilities weekly using Hebb's Williams and Radial arm mazes. Using ELISA, we measured plasma and brain oxysterols, transforming growth factor β, amyloid β, matrix metalloproteinase-9, claudin-5, and ATP Binding Cassette Transporter A1 expressions biweekly. The concentrations high density lipoprotein, low density lipoprotein, aspartate aminotransferase, and alanine transaminase were assessed using diagnostic kits, while the antioxidant profile was determined using UV spectroscopy. Our results indicated a synergistic increase in oxysterols, transforming growth factor β, amyloid β, matrix metalloproteinase-9, low density lipoprotein, aspartate aminotransferase, and alanine transaminase, with a concomitant decrease in the experimental animals' Claudin-5, ATP Binding Cassette Transporter A1, high density lipoprotein and antioxidant regulations. These findings suggest that a high-cholesterol diet may lead to oxysterol buildup, resulting in amyloid β accumulation due to transforming growth factor β hyperactivation. In conclusion, our study highlights the need to explore the role of oxysterols in the pathogenesis of Alzheimer's disease. By uncovering potential mechanisms underlying the interplay of oxysterols with fibrotic mediators, our study may pave the way for developing novel therapeutic approaches to manage Alzheimer's disease.

Source: Brain Disorders

DOI: 10.1016/j.dscb.2025.100206

Authors: Ashmita Das, Durlav Chowdhury, Dilip Sharma, Rahul Manna, Surendra H. Bodakhe

Institutions: Guru Ghasidas Vishwavidyalaya, Rutgers, The State University of New Jersey, Rutgers New Jersey Medical School, Institute of Post Graduate Medical Education and Research

Language: English

Topic: Alzheimer's disease research and treatments

Subfield: Physiology

Field: Medicine

Domain: Health Sciences

SDG: Good health and well-being

Open Access status: gold

Estimated APC paid: $1,810