β-Amyloid deposition in brain is enhanced in mouse models of arterial hypertension

• Published in: Neurobiology of aging Vol. 30; no. 2; pp. 222 - 228
• Main Authors: Gentile, Maria Teresa, Poulet, Roberta, Pardo, Alba Di, Cifelli, Giuseppe, Maffei, Angelo, Vecchione, Carmine, Passarelli, Francesca, Landolfi, Alessandro, Carullo, Pierluigi, Lembo, Giuseppe
• Format: Journal Article
• Language: English
• Published: London Elsevier Inc 01.02.2009; Elsevier
• Subjects: Amyloid beta-Peptides - metabolism; Animals; Biological and medical sciences; Blood-Brain Barrier - metabolism; Blood–brain barrier; Brain; Brain - metabolism; Cerebral circulation. Blood-brain barrier. Choroid plexus. Cerebrospinal fluid. Circumventricular organ. Meninges; Development. Senescence. Regeneration. Transplantation; Disease Models, Animal; Fundamental and applied biological sciences. Psychology; Humans; Hypertension; Hypertension - metabolism; Hypertension - therapy; Immunotherapy; Internal Medicine; Male; Mice; Mice, Inbred C57BL; Neurology; Tissue Distribution; Treatment Outcome; Vertebrates: nervous system and sense organs; β-Amyloid; Hypertension; β-Amyloid; Brain; Immunotherapy; Blood–brain barrier; Animal model; Senescence; Rodentia; Central nervous system; Blood brain barrier; Encephalon; Vertebrata; Mammalia; Mouse; Blood-brain barrier; β Amyloid protein; Animal
• ISSN: 0197-4580; 1558-1497
• DOI: 10.1016/j.neurobiolaging.2007.06.005

Abstract 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 β-amyloid (Aβ) 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 Aβ. 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-Aβ antibodies and the presence of Aβ-like fragments. Finally, we analyzed mice after passive immunotherapy with anti-Aβ IgG. We observed that this latter approach determined a markedly reduced Aβ immunopositivity in both cortex and hippocampus. Our study demonstrates that chronic hypertension determines an impairment of the blood–brain barrier permeability with deposition of Aβ in brain tissue and that passive immunotherapy prevents this latter phenomenon.