Pittsburgh compound-B (PiB), an amyloid-binding positron emission tomography (PET) tracer, is widely used for imaging amyloid-β in those with and at risk for Alzheimer disease. Here, we report on an otherwise normal 68-year-old female with abnormally high and very focal PiB retention. Coregistered T1-weighted magnetic resonance imaging and dynamic 2-fluoro-2-deoxy-D-glucose (FDG) images confirmed that the focal PiB enhancement was in the superior sagittal and transverse sinuses, outside of the adjacent cortex. Flow through the venous vasculature was normal as assessed by dynamic FDG PET imaging. These features supported the conclusion that PiB retention was not simply due to a hemodynamic abnormality, but may have represented PiB binding to fibrillar deposits of a β-sheet protein (ie, amyloid), whose nature is currently unclear.

Presenilins are polytopic, integral proteins that control intramembranous proteolysis at the "gamma-" and "epsilon-" cleavage sites of the Alzheimer amyloid-beta precursor protein (APP) to yield amyloid-beta peptide (Abeta) and the APP intracellular domain (AICD). We have overexpressed a constitutively active, pathogenic form of PS1 (known as PS1 Delta exon 9) together with its substrate, APP-C99, in Spodoptera frugiperda (Sf9) cells. Sf9 cells have been reported to lack endogenous gamma-secretase, an unexpected finding since there exists an insect homologue of PS1. In our hands, neither intact insect cells coexpressing PS1 Delta exon 9/APP-C99 nor the aqueous homogenates of these cells displayed obvious products of the gamma- or epsilon-secretase reactions, as reported. Surprisingly, when APP-C99-expressing cells were homogenized in 3[(3-cholamidopropyl) dimethylammonio]-2-hydroxypropanesulfonic acid (CHAPSO), a detergent known to support gamma-secretase activity, subsequent incubation led to the accumulation of an AICD-like peptide (AICD-L). Aspartyl proteinase inhibitors were effective in preventing the appearance of AICD-L, but inhibitors of other classes of proteinases were ineffective. Immunoprecipitation-mass spectrometry of AICD-L revealed its identity as the minor of the two known AICDs.

Department of Neurology and Center for Neuroscience, University of California at Davis, Sacramento, CA Reprints: Charles DeCarli, MD, Department of Neurology and Center for Neuroscience, University of California at Davis, 4860 Y Street, Suite 3700, Sacramento, CA 95817 (e-mail: [email protected]).

Black caregivers of persons with Alzheimer disease and related dementias (ADRD) have demonstrated significantly lower levels of stress and burden than white caregivers, as measured by instruments that assess caregiving burden and stressfulness of specific problem behaviors. However, the reasons for reported differences are unclear and cannot be attributed solely to race. This descriptive study used content analysis to compare black caregivers' descriptions and interpretations of responses to memory and behavioral issues of relatives with ADRD to 11 explanations for lower levels of upset proposed in the caregiving literature. Findings confirmed only two explanations from the literature, social support and religious orientation, as factors that influenced appraisal of upset. Two new themes emerged, categorized as Making Sense and Using Strategies, as explanatory frameworks. Findings extend current knowledge of black caregivers' emotional responses to caregiving and support the need for future study of the ways in which particular ethnic and racial groups experience caregiving. Understanding the meaning of appraisals may enable service providers and program developers to tailor services and interventions to support the efforts of black and other minority caregivers.

Alzheimer's Disease Center and Imaging of Dementia and Aging (IDeA) Laboratory, Department of Neurology, Center for Neuroscience, University of California, Sacramento, CA

Bristow, Karrah Q.*; Au, Rhoda*; Massaro, Joseph M.† ‡; Seshadri, Sudha*; Wolf, Philip A.*; Kelly-Hayes, Margaret*; DeCarli, Charles§ Author Information

During the first two decades of the life of this Journal (ADAD) much progress has been made in our understanding of Alzheimer disease (AD). Advancing knowledge, however, has been accompanied by increasing appreciation of the complexity and heterogeneity of this disease. Prevention and cure continue to elude us as the number of afflicted and the cost of their care continues to increase. New techniques together with long-term prospective follow-up studies, as well as utilization of data accumulated in existing data bases, are needed to move the field forward. We expect that during the next two decades, as new information accrues, reports published in ADAD will continue to contribute to the dissemination and elucidation of critical issues in Alzheimer research.

Alzheimer Disease & Associated Disorders: July 2005 - Volume 19 - Issue 3 - p 162 doi: 10.1097/01.wad.0000175524.91480.84