Reduction of the cerebrovascular volume in a transgenic mouse model of Alzheimer's disease.
Combined evidence from neuroimaging and neuropathological studies shows that signs of vascular pathology and brain hypoperfusion develop early in Alzheimer's disease (AD). To investigate the functional implication of these abnormalities, we have studied the cerebrovascular volume and selected markers of blood-brain barrier (BBB) integrity in 11-month-old 3 x Tg-AD mice, using the in situ brain perfusion technique. The cerebrovascular volume of distribution of two vascular space markers, [3H]-inulin and [14C]-sucrose, was significantly lower (-26% and -27%, respectively; p < 0.01) in the brain of 3 x Tg-AD mice compared to non-transgenic littermates. The vascular volume reduction was significant in the hippocampus (p < 0.01), but not in the frontal cortex and cerebellum. However, the brain transport coefficient (Clup) of [14C]-D-glucose (1 microM) and [3H]-diazepam was similar between 3xTg-AD mice and controls, suggesting no difference in the functional integrity of the BBB. We also report a 32% increase (p < 0.001) in the thickness of basement membranes surrounding cortical microvessels along with a 20% increase (p < 0.05) of brain collagen content in 3xTg-AD mice compared to controls. The present data indicate that the cerebrovascular space is reduced in a mouse model of Abeta and tau accumulation, an observation consistent with the presence of cerebrovascular pathology in AD.
Bourasset
Fanchon
F
Paris-Sud 11 University, EA2706, Faculty of Pharmacy, Châtenay-Malabry, France.
Ouellet
Mélissa
M
Tremblay
Cyntia
C
Julien
Carl
C
Do
Tuan Minh
TM
Oddo
Salvatore
S
LaFerla
Frank
F
Calon
Frédéric
F
D000544:Alzheimer Disease / Q000378:metabolism / Q000473:pathology*; D016229:Amyloid beta-Peptides / Q000378:metabolism; D000818:Animals; D001485:Basement Membrane / Q000378:metabolism / Q000648:ultrastructure; D001808:Blood Vessels / Q000378:metabolism / Q000473:pathology*; D001921:Brain / Q000473:pathology; D001923:Brain Chemistry / Q000187:drug effects; D002560:Cerebrovascular Circulation / Q000502:physiology*; D024042:Collagen Type I / Q000378:metabolism; D024141:Collagen Type IV / Q000378:metabolism; D003975:Diazepam / Q000378:metabolism; D018757:GABA Modulators / Q000378:metabolism; D005947:Glucose / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D051379:Mice; D008822:Mice, Transgenic; D016875:tau Proteins / Q000378:metabolism
D016229:Amyloid beta-Peptides; D024042:Collagen Type I; D024141:Collagen Type IV; D018757:GABA Modulators; D016875:tau Proteins; D005947:Glucose; D003975:Diazepam