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

TitleAltered cerebral vascular volumes and solute transport at the blood-brain barriers of two transgenic mouse models of Alzheimer's disease.
Publication TypeJournal Article
Year of Publication2014
AuteursDo, TMinh, Alata, W, Dodacki, A, Traversy, M-T, Chacun, H, Pradier, L, Scherrmann, J-M, Farinotti, R, Calon, F, Bourasset, F
JournalNeuropharmacology
Volume81
Pagination311-7
Date Published2014 Jun
ISSN1873-7064
KeywordsAge Factors, Alzheimer Disease, Amyloid beta-Protein Precursor, Animals, Blood-Brain Barrier, Brain, Cerebrovascular Circulation, Diazepam, Disease Models, Animal, Functional Laterality, Glucose, Glucose Transporter Type 1, Humans, Mice, Mice, Transgenic, Microvessels, Mutation, Presenilin-1, Sucrose, tau Proteins
Abstract

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 [(3)H]-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.

DOI10.1016/j.neuropharm.2014.02.010
Alternate JournalNeuropharmacology
PubMed ID24631967