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Blood—Brain Barrier Permeability Precedes Senile Plaque Formation in an Alzheimer Disease Model
Author(s) -
UJIIE MAKI,
DICKSTEIN DARA L.,
CARLOW DOUGLAS A.,
JEFFERIES WILFRED A.
Publication year - 2003
Publication title -
microcirculation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.793
H-Index - 83
eISSN - 1549-8719
pISSN - 1073-9688
DOI - 10.1038/sj.mn.7800212
Subject(s) - blood–brain barrier , senile plaques , disease , pathology , alzheimer's disease , medicine , permeability (electromagnetism) , chemistry , central nervous system , biochemistry , membrane
Objective : To establish the generality of cerebrovascular pathology frequently observed with Alzheimer disease, we have assessed blood‐brain barrier (BBB) integrity using the Alzheimer disease model Tg2576 mice in which cognitive deficits and neuritic plaque formation develop around 10–12 months of age. Methods : We assessed BBB integrity using well‐established methods involving albumin and Evans blue uptake and introduce the use of a novel perfusion protocol using succinimidyl ester of carboxyfluorescein diacetate. Results : BBB permeability is increased in the cerebral cortex of 10‐month‐old Tg2576 mice preceding Alzheimer disease pathology presentation. Furthermore, when compared with their nontransgenic littermates, 4‐month‐old Tg2576 mice exhibit compromised BBB integrity in some areas of the cerebral cortex. An age‐related increase in albumin uptake by the brains of Tg2576 mice, compared with nontransgenic mice, was also observed. These findings were supported by quantitative Evans blue analysis ( p = 0.07, two‐way analysis of variance). Conclusion : A breakdown of BBB was evident in young 4‐ to 10‐month‐old Tg2576 mice. Compromised barrier function could explain the mechanisms of Aβ entry into the brain observed in experimental Alzheimer disease vaccination models. Such structural changes to the BBB caused by elevated Aβ could play a central role in Alzheimer disease development and might define an early point of intervention for designing effective therapy against the disease.