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

作者：Do Tuan Minh; Alata Wael; Dodacki Agnes; Traversy Marie Therese; Chacun Helene; Pradier Laurent; Scherrmann Jean Michel; Farinotti Robert; Calon Frederic; Bourasset Fanchon^*

来源：Neuropharmacology, 2014, 81: 311-317.

DOI：10.1016/j.neuropharm.2014.02.010

• Alzheimer's disease
• 3xTg-AD
• APP/PS1
• Blood-brain barrier integrity
• In situ brain perfusion
• Brain vascular volume

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 (V-vasc) was sub-normal in 3xTg-AD mice aged from 6 to 18 months, but not in the APP/PSI mice. The uptakes of [H-3]-diazepam by the brains of 3xTg-AD, APP/PSI 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 18month 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/PSI mice suggests that hyperphosphorylated tau proteins contribute to the vascular changes that occur in AD.

• 出版日期2014-6