Beta-amyloid deposition in brain is enhanced in mouse models of arterial hypertension.
There are conflicting evidence regarding the association of hypertension with Alzheimer's disease (AD), and so far it is still unexplored whether increased blood pressure levels can be mechanistically related to the pathophysiology of AD. Since the deposition of beta-amyloid (A beta) in brain represents the first pathogenetic event in the onset of AD, in this study we investigated the role of hypertension in the brain deposition of A beta. We analyzed two independent mouse models of hypertension. In both models we observed an increased permeability of blood-brain barrier in cortex and hippocampus. More interestingly, in the same areas hypertensive mice showed a marked positivity to anti-A beta antibodies and the presence of A beta-like fragments. Finally, we analyzed mice after passive immunotherapy with anti-A beta IgG. We observed that this latter approach determined a markedly reduced A beta immunopositivity in both cortex and hippocampus. Our study demonstrates that chronic hypertension determines an impairment of the blood-brain barrier permeability with deposition of A beta in brain tissue and that passive immunotherapy prevents this latter phenomenon.
Gentile
Maria Teresa
MT
Department of Angio-Cardio-Neurology, IRCCS Neuromed, 86077 Pozzilli, IS, Italy.
Poulet
Roberta
R
Di Pardo
Alba
A
Cifelli
Giuseppe
G
Maffei
Angelo
A
Vecchione
Carmine
C
Passarelli
Francesca
F
Landolfi
Alessandro
A
Carullo
Pierluigi
P
Lembo
Giuseppe
G
D016229:Amyloid beta-Peptides / Q000378:metabolism*; D000818:Animals; D001812:Blood-Brain Barrier / Q000378:metabolism*; D001921:Brain / Q000378:metabolism*; D004195:Disease Models, Animal; D006801:Humans; D006973:Hypertension / Q000378:metabolism* / Q000628:therapy*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D014018:Tissue Distribution; D016896:Treatment Outcome
D016229:Amyloid beta-Peptides