Human hepatocytes were transplanted into urokinase-type plasminogen activator-transgenic SCID mice (uPA/SCID mice), which are immunodeficient and undergo liver failure. The transplanted cells were characterized in terms of their in vivo growth potential and functions. The human hepatocytes progressively repopulated the murine host liver. However, the recipients died when the replacement index (RI) of the human hepatocytes exceeded 50%. The hosts (chimeric mice) survived at RI >50% when treated with a drug that has anti-human complement factor activity, and these mice developed livers with RI values as high as 96%. In total, 36 chimeric mice were generated, and the rate of successful engraftment was as high as 92%. The yield of chimeric mice with RI >70% was 32%. The human hepatocytes in the murine host liver expressed mRNAs for a variety of human cytochrome P450 (hCYP) subtypes, in a manner that was similar to the donor liver. The mRNAs for hCYP3A4 and hCYP1A1/2 were induced in the liver in a CYP type-specific manner when the mice were treated with rifampicin and 3-methylcholanthrene, respectively. These results indicate that human hepatocytes that propagate in mice retain their normal pharmacological responses. We conclude that the chimeric mouse developed in the present study is a useful model for assessing the functions and pharmacological responses of human hepatocytes.

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It is recognized that individuals with mild cognitive impairment (MCI) already demonstrate difficulty in aspects of daily functioning, which predicts disease progression. This study examined the relationship between self- versus informant-report of functional ability, and how those reports relate to objective disease measures across the disease spectrum (i.e. cognitively normal, MCI, Alzheimer’s disease). A total of 1,080 subjects with self- and/or informant-rated Everyday Cognition (ECog) questionnaires were included. Objective measures included cognitive functioning, structural brain atrophy, cerebrospinal fluid (CSF) abnormalities, and a marker of amyloid deposition using positron emission tomography (PET) with [18F]AV45 (florbetapir). Overall, informant-report was consistently more associated with objective markers of disease than self-report although self-reported functional status may still have some utility in early disease.

INTRODUCTION The Alzheimer’s Disease Neuroimaging Initiative (ADNI) is a multi-site study designed to characterize the trajectories of biomarkers across the aging process. We present ADNI Biostatistics Core analyses that integrate data over the length, breadth, and depth of ADNI. METHODS Relative progression of key imaging, fluid, and clinical measures was assessed. Individuals with subjective memory complaints (SMC) and early mild cognitive impairment (eMCI) were compared to normal controls, MCI and individuals with Alzheimer’s disease. Amyloid imaging and magnetic resonance imaging (MRI) summaries were assessed as predictors of disease progression. RESULTS Relative progression of markers supports parts of the amyloid cascade hypothesis, although evidence of earlier occurrence of cognitive change exists. SMC are similar to normal controls, while eMCI fall between the cognitively normal and MCI groups. Amyloid leads to faster conversion and increased cognitive impairment. DISCUSSION Analyses support features of the amyloid hypothesis, but also illustrate the considerable heterogeneity in the aging process.