Faculty Bibliography

The outbreak of new variant Creutzfeldt-Jakob disease has raised the specter of a potentially large population being at risk to develop this prionosis. None of the prionoses currently have an effective treatment. Recently, vaccination has been shown to be effective in mouse models of another neurodegenerative condition, namely Alzheimer's disease. Here we report that vaccination with recombinant mouse prion protein delays the onset of prion disease in mice. Vaccination was performed both before peripheral prion exposure and after exposure. A delay in disease onset was seen in both groups, but was more prolonged in animals immunized before exposure. The increase in the incubation period closely correlated with the anti-prion protein antibody titer. This promising finding suggests that a similar approach may work in humans or other mammalian species at risk for prion disease

Cerebral amyloid angiopathy defines the deposition of amyloid fibrils in the walls of medium- and small-size leptomeningeal and cortical arteries and arterioles. This condition is an important cause of cerebral hemorrhages and is also associated with cerebral infarctions and diffused white matter changes. In many instances, vascular amyloid deposits co-exist with intraneuronal neurofibrillary tangles, being the cognitive areas the most severely affected. However, the importance of cerebral amyloid angiopathy as a causative element in the process of neurodegeneration is still debatable. This review discusses inherited dementia syndromes associated with neuronal loss and amyloid deposition in the brain, with particular focus on familial Alzheimer's disease and chromosome 13 dementia. (c) 2002 Prous Science. All rights reserved

Squirrel monkey is a valuable model to study pathogenesis of cerebrovascular amyloid angiopathy (CAA). Previous studies suggested that circulating amyloid-beta40 peptide (Abeta40) crosses the blood-brain barrier (BBB) and may therefore enhance cerebrovascular amyloidosis in aged squirrel monkeys. In the present study, we used single photon emission computed tomography (SPECT) to determine elimination of 123I-Abeta40 and 99mTc-DTPA, an extracellular marker, from the brain in squirrel monkeys at different age. Following intracerebral microinfusions, the time-activity brain clearance curves indicated bi-exponential removal of 123I-Abeta40 with an initial rapid washout (1.1 < or = t 1/2 < or = 2.7 h). This, plus the observed appearance of 123I-radioactivity in plasma suggest significant brain-to-blood transport. In contrast, 99mTc-DTPA was removed slowly by brain interstitial fluid bulk flow (monoexponential decay with 6.8 < or = t 1/2 < or = 16.8 h). A comparison of three middle aged (11-16 years old) vs. two old (22 yrs old) monkeys was consistent with an age-related decline in the BBB capacity to remove 123I-Abeta from the brain. This correlated with an age-dependent increase in A1beta40/42 cerebrovascular immunoreactivity and amyloid deposition. Thus, vascular clearance plays an important role in reducing Abeta levels in the squirrel monkey brain and impaired Abeta40 elimination across the BBB may contribute to the development of CAA