Altered cerebral vascular volumes and solute transport at the blood–brain barriers of two transgenic mouse models of Alzheimer's disease

• The BBB is altered in 3xTg-AD but not in APP/PS1 mice.
• The protein Tau could be involved in the BBB modifications occurring in 3xTg-AD mice.
• Brain vascular volume is reduced early in 3xTg-AD mice (before plaques and tangles).
• The d-glucose uptake and brain capillary amounts of Glut-1 are reduced at the later stage of the AD pathology (18 months).

We evaluated the integrity and function of the blood–brain barrier in 3xTg-AD mice aged 3–18 months and in APP/PS1 mice aged 8-months to determine the impacts of changes in amyloid and tau proteins on the brain vascular changes. The vascular volume (Vvasc) was sub-normal in 3xTg-AD mice aged from 6 to 18 months, but not in the APP/PS1 mice. The uptakes of [3H]-diazepam by the brains of 3xTg-AD, APP/PS1 and their age-matched control mice were similar at all the times studied, suggesting that the simple diffusion of small solutes is unchanged in transgenic animals. The uptake of d-glucose by the brains of 18-month old 3xTg-AD mice, but not by those of 8-month old APP/PS1 mice, was reduced compared to their age-matched controls. Accordingly, the amount of Glut-1 protein was 1.4 times lower in the brain capillaries of 18 month-old 3xTg-AD mice than in those of age-matched control mice. We conclude that the brain vascular volume is reduced early in 3xTg-AD mice, 6 months before the appearance of pathological lesions, and that this reduction persists until they are at least 18 months old. The absence of alterations in the BBB of APP/PS1 mice suggests that hyperphosphorylated tau proteins contribute to the vascular changes that occur in AD.