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O3‐07‐03: Alzheimer disease cooperative study (ADCS) home based assessment: Designing trials with new technology
Author(s) -
Sano Mary,
Egelko Susan,
Ferris Steven,
Kaye Jeffrey,
Hayes Tamara,
Mundt James,
Reyes Tracy,
Donohue Michael,
Sun ChungKai,
Whitehair Danielle,
Stokes Karen,
Aisen Paul
Publication year - 2011
Publication title -
alzheimer's and dementia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.713
H-Index - 118
eISSN - 1552-5279
pISSN - 1552-5260
DOI - 10.1016/j.jalz.2011.05.1434
Subject(s) - medicine , randomized controlled trial , dementia , clinical trial , cognitive assessment system , cohort , montreal cognitive assessment , physical therapy , cognition , cognitive impairment , disease , psychiatry
Cerebral blood flow (CBF) response evoked by whisker stimulation was monitored by laser Doppler flowmetry. Vasomotor responses were evaluated on isolated pressurized segments of middle cerebral artery using online videomicroscopy. Amyloid plaques burden and tissue levels of Ab were measured using Thioflavin-S staining, anti-Ab immunolabelling and ELISA. Results:B1r appeared increased in APPmice, particularly in the hippocampus, where double immunostaining showed its expression by activated astrocytes (GFAP), but not microglia (CD11b), surrounding Ab deposits. Learning and memory were significantly improved after 5 and 10 weeks of SSR240612 treatment. These treatments also ameliorated evoked CBF responses. Both treatments completely rescued dilations to acetylcholine. In treated wild-type (WT) mice, however, contractions induced by endothelin-1 and NO synthesis inhibition were significantly reduced compared to untreated WT. BK elicited a biphasic response (contraction followed by relaxation) in all groups, with a tendency to constrict and dilate more in APP and treated WT mice, respectively. Finally, soluble Ab1-42 levels andAb plaque load were significantly reduced in the brain of APPmice after both treatments.Conclusions: Together, these data support a role of the kallikrein-kinin system in the pathogenesis of AD, and suggest that it may represent a new therapeutic target.