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

• Published in: Neuropharmacology 2014-06, Vol.81, p.311-317
• Main Authors: Do, Tuan Minh, Alata, Wael, Dodacki, Agnès, Traversy, Marie-Thérèse, Chacun, Hélène, Pradier, Laurent, Scherrmann, Jean-Michel, Farinotti, Robert, Calon, Frédéric, Bourasset, Fanchon
• Format: Article
• Language: English
• Subjects: 3xTg-AD; Age Factors; Alzheimer Disease - genetics; Alzheimer Disease - pathology; Alzheimer's disease; Amyloid beta-Protein Precursor - genetics; Animals; APP/PS1; Blood-Brain Barrier - metabolism; Blood-Brain Barrier - physiology; Blood–brain barrier integrity; Brain - drug effects; Brain - metabolism; Brain - pathology; Brain vascular volume; Cerebrovascular Circulation - genetics; Diazepam - metabolism; Disease Models, Animal; Functional Laterality; Glucose - metabolism; Glucose Transporter Type 1 - metabolism; Humans; In situ brain perfusion; Mice; Mice, Transgenic; Microvessels - pathology; Microvessels - physiopathology; Mutation - genetics; Presenilin-1 - genetics; Sucrose - metabolism; tau Proteins - genetics
• ISSN: 0028-3908; 1873-7064
• DOI: 10.1016/j.neuropharm.2014.02.010

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. •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).