Differential effects of high-sucrose and high-fat diets on metabolic syndrome, BBB integrity, and hippocampal Aβ accumulation.

Metabolic syndrome (MS) is a global health problem and a recognized risk factor for cognitive impairment and Alzheimer's disease (AD), but the different effects of specific dietary components on MS-related neurological damage remain unclear. This study investigated the effects of long-term high-calorie diets on metabolic parameters, blood-brain barrier (BBB) ​​integrity, and hippocampal β-amyloid (Aβ) accumulation. Male Wistar rats were fed a control diet, a high-sucrose diet (HSD, 30% sucrose in drinking water), or a high-fat diet (HFD, 30% lard) for 12 months. The study assessed metabolic syndrome parameters, spatial memory (Morris water maze), BBB permeability (Evans blue staining), tight junction proteins (ZO-1, Occludin), and the levels of Aβ and its transporters (LRP1, RAGE). The results showed that both HSD and HFD induced central obesity, increased BBB permeability, and spatial memory deficits in rats; however, disruption of the blood-brain barrier was not associated with changes in tight junction protein expression. Notably, hippocampal Aβ accumulation increased only in the high-fat diet group (HFD group) after 8-12 months, associated with a significant downregulation of the Aβ clearance receptor LRP1, while no changes were observed in RAGE. In contrast, the high-fat diet group (HSD group) exhibited more extensive metabolic syndrome-related alterations, including hyperglycemia and hypertension. Our results suggest that while both sucrose- and fat-based high-calorie diets impair the integrity of the blood-brain barrier and cognitive function, only high-fat intake promotes hippocampal Aβ accumulation by downregulating LRP1. These results suggest that although both dietary patterns contribute to metabolic syndrome and cognitive impairment, high-fat intake may pose a more specific risk to Alzheimer's disease pathology.