# An Acebuche Oil-Enriched Diet Prevents Early-Stage Cerebrovascular Alterations in the 5xFAD Mouse Model of Alzheimer’s Disease

## TL;DR

A diet enriched with Acebuche oil, a type of olive oil rich in antioxidants, may help prevent early signs of Alzheimer’s disease in mice.

## Contribution

This study demonstrates that an Acebuche oil-enriched diet can delay early cerebrovascular and pathological changes in a mouse model of Alzheimer’s disease.

## Key findings

- The ACE oil-enriched diet prevented early-stage cerebrovascular alterations in 5xFAD mice.
- ACE oil delayed Aβ accumulation, hypoxia, BBB breakdown, and cognitive deficits in the mouse model.
- Systemic metabolic changes, like hepatic steatosis, occurred in mice on the ACE oil diet at 6 months.

## Abstract

Background/Objectives: Alzheimer’s disease (AD) is a neurodegenerative disorder in which altered microvascular circulation participates in the pathogenesis. The lack of therapeutic treatments for AD makes the development of strategies aimed at preventing or delaying the disease onset urgent. In recent years, several studies have highlighted that a diet rich in antioxidants and anti-inflammatory compounds may positively impact AD development. In this study, we assessed the impact of a diet enriched with Acebuche (ACE) oil, an extra-virgin olive oil particularly rich in antioxidants and anti-inflammatory compounds, on AD progression in the 5xFAD mouse model. Methods: After weaning, wild-type (WT) and 5xFAD mice received the standard or the ACE oil-enriched diet. At 2, 4 and 6 months, the effects of the diet were evaluated on AD-related microvascular aberrancies, beta-amyloid (Aβ) formation, hypoxic state, blood–brain barrier (BBB) alterations, neuroinflammation and cognitive impairment. Metabolic parameters were also evaluated. Results: In 5xFAD mice, the ACE oil-enriched diet prevented alterations in cerebral microcirculation. Moreover, Aβ accumulation, downregulation of Aβ-degrading enzymes, hypoxia, BBB breakdown, neuroinflammation, and cognitive deficits were delayed by the ACE oil-enriched diet. However, some of these effects were reduced at 6 months, in concomitance with systemic metabolic changes, such as hepatic steatosis, evidenced in both WT and 5xFAD mice receiving the ACE oil-enriched diet. Conclusions: Overall, the present results represent proof of concept for the validity of early dietary interventions in AD prevention.