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Cholesterol and docosahexenoic acid (DHA) may affect degenerative processes in Alzheimer's Disease (AD) by influencing Abeta metabolism indirectly via the vasculature. We investigated whether DHA-enriched diets or cholesterol-containing Typical Western Diets (TWD) alter behavior and cognition, cerebral hemodynamics (relative cerebral blood volume (rCBV)) and Abeta deposition in 8- and 15-month-old APP(swe)/PS1(dE9) mice. In addition we investigated whether changes in rCBV precede changes in Abeta deposition or vice versa. Mice were fed regular rodent chow, a TWD-, or a DHA-containing diet. Behavior, learning and memory were investigated, and rCBV was measured using contrast-enhanced MRI. The Abeta load was visualized immunohistochemically. We demonstrate that DHA altered rCBV in 8-month-old APP/PS1 and wild type mice[AU1]. In 15-month-old APP/PS1 mice DHA supplementation improved spatial memory, decreased Abeta deposition and slightly increased rCBV, indicating that a DHA-enriched diet can diminish AD-like pathology. In contrast, TWD diets decreased rCBV in 15-month-old mice. The present data indicate that long-term dietary interventions change AD-like pathology in APP/PS1 mice. Additionally, effects of the tested diets on vascular parameters were observed before effects on Abeta load were noted. These data underline the importance of vascular factors in the APP/PS1 mouse model of AD pathology.

High dietary cholesterol and low dietary docosahexaenoic acid (DHA) intake are risk factors for Alzheimer's disease (AD). However, it is unclear how these components influence the course of the disease. We investigated the effects of dietary lipids on beta-amyloid deposition and blood circulation in the brains of 18-month-old APP/PS1 mice. Starting at 6 months of age, mice were fed a regular rodent chow, a Typical Western Diet (TWD) containing 1% cholesterol, or a diet with a high (0.5%) level of DHA for 12 months. Relative cerebral blood volume (rCBV) and flow (CBF) were determined with (2)H MR spectroscopy and gradient echo contrast enhanced MRI. Deposition of beta-amyloid was visualized in fixed brain tissue with immunohistochemistry. The TWD diet increased plaque burden in the dentate gyrus of the hippocampus, but did not significantly reduce rCBV. In contrast, the DHA-enriched diet increased rCBV without changing blood flow indicating a larger circulation in the brain probably due to vasodilatation and decreased the amount of vascular beta-amyloid deposition. Together, our results indicate that the long-term intake of dietary lipids can impact both brain circulation and beta-amyloid deposition, and support the involvement of hemodynamic changes in the development of AD.