title: Altered cerebral vascular volumes and solute transport at the blood-brain barriers of two transgenic mouse models of Alzheimer's disease.
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.
authors.affiliation: Laboratoire de Pharmacie Clinique et pharmacocinétique, EA 4123, Université Paris-Sud 11, Faculté de Pharmacie, Châtenay-Malabry, France.
authors.forename: Tuan Minh
authors.initials: TM
authors.lastname: Do
authors.affiliation: Faculty of Pharmacy, Laval University, Quebec, QC, Canada.
authors.forename: Wael
authors.initials: W
authors.lastname: Alata
authors.affiliation: Inserm, U1144, Paris F-75006, France; Université Paris Descartes, UMR-S 1144, Paris F-75006, France; Université Paris Diderot, UMR-S 1144, Paris F-75013, France.
authors.forename: Agnès
authors.initials: A
authors.lastname: Dodacki
authors.affiliation: Faculty of Pharmacy, Laval University, Quebec, QC, Canada.
authors.forename: Marie-Thérèse
authors.initials: MT
authors.lastname: Traversy
authors.affiliation: CNRS UMR 8612, Université Paris Sud, Faculté de Pharmacie, Châtenay-Malabry, France.
authors.forename: Hélène
authors.initials: H
authors.lastname: Chacun
authors.affiliation: Sanofi-Aventis Therapeutic Strategy Unit Aging, Chilly-Mazarin, France.
authors.forename: Laurent
authors.initials: L
authors.lastname: Pradier
authors.affiliation: Inserm, U1144, Paris F-75006, France; Université Paris Descartes, UMR-S 1144, Paris F-75006, France; Université Paris Diderot, UMR-S 1144, Paris F-75013, France.
authors.forename: Jean-Michel
authors.initials: JM
authors.lastname: Scherrmann
authors.affiliation: Laboratoire de Pharmacie Clinique et pharmacocinétique, EA 4123, Université Paris-Sud 11, Faculté de Pharmacie, Châtenay-Malabry, France.
authors.forename: Robert
authors.initials: R
authors.lastname: Farinotti
authors.affiliation: Faculty of Pharmacy, Laval University, Quebec, QC, Canada.
authors.forename: Frédéric
authors.initials: F
authors.lastname: Calon
authors.affiliation: Inserm, U1144, Paris F-75006, France; Université Paris Descartes, UMR-S 1144, Paris F-75006, France; Université Paris Diderot, UMR-S 1144, Paris F-75013, France. Electronic address: fanchon.bourasset@parisdescartes.fr.
authors.forename: Fanchon
authors.initials: F
authors.lastname: Bourasset
mesh_terms: D000367:Age Factors; D000544:Alzheimer Disease / Q000235:genetics / Q000473:pathology*; D016564:Amyloid beta-Protein Precursor / Q000235:genetics; D000818:Animals; D001812:Blood-Brain Barrier / Q000378:metabolism* / Q000502:physiology*; D001921:Brain / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D002560:Cerebrovascular Circulation / Q000235:genetics*; D003975:Diazepam / Q000378:metabolism; D004195:Disease Models, Animal; D007839:Functional Laterality; D005947:Glucose / Q000378:metabolism; D051272:Glucose Transporter Type 1 / Q000378:metabolism*; D006801:Humans; D051379:Mice; D008822:Mice, Transgenic; D055806:Microvessels / Q000473:pathology / Q000503:physiopathology; D009154:Mutation / Q000235:genetics; D053764:Presenilin-1 / Q000235:genetics; D013395:Sucrose / Q000378:metabolism; D016875:tau Proteins / Q000235:genetics
chemical_list: D016564:Amyloid beta-Protein Precursor; D051272:Glucose Transporter Type 1; C508853:PSEN1 protein, human; D053764:Presenilin-1; C495678:Slc2a1 protein, mouse; D016875:tau Proteins; D013395:Sucrose; D005947:Glucose; D003975:Diazepam
keywords: 3xTg-AD; APP/PS1; Alzheimer's disease; Blood–brain barrier integrity; Brain vascular volume; In situ brain perfusion