These data indicate that GFP can be used to select for transduced BMCs in vitro, expressed in multiple bone marrow-derived cell lineages, used to select transduced cells, and follow the fate of transduced cells long-term in vivo.

Alzhemer disease patients exhibit irregularities in the patterns of normaly circadian (daily) rhythms.Alzheimer-type pathology has been reported in the hypothalamus and in the suprachiamatic nuclei, the putative site of the circadian oscillator. We examine the relationship between the neuropathology of AMzheimer disease, as modeled by an animal system, and circadian dysregulation by grafing genetically transformed cells that overexpress .3/A4 amyloid into the sup a nuclei of adult rats. Grafts of /A4-positive cells, but not of control cells, significantly altered the pattern of activity of implanted rats. Although experimental conditions included light-dark cycles that normally tend to drive rats to 24-h rhythms, animals with grafts of O/A4-positive cells showed abnormally h levels ofactivity during the light phase in addition to a disrupted circadian pattern. Periodogram analysis demonstrated sgn t rhythms outside of a circadian range. The body temperature rhythm ofthese animals was also weak 6 weeks after gfting; however, unlike activity patterns, body temperature regained a circadian period by 8 weeks after cell implantation. These data indicate that disruption of circadian activity Is a behavioral measure of the consequences of (3/A4 accumulaton in brain implants.Alzheimer disease (AD) is a progressive dementing illness of the elderly, characterized by a dramatic decline in cognitive function (1). However, the behavioral abnormalities of AD are not limited to cognitive deficits. Irregular patterns of normally circadian (24 h) rhythms are also observed and the severity of dementia has been correlated with the degree of disturbance in the circadian rest-activity rhythm (2). As a consequence, the circadian pattern of sleep-wake cycles (3) and activity (4) that are disrupted in AD hinder clinical management (5). Studies on the interaction of cognition and the circadian system suggest that abnormal rhythms may contribute to the decline in mental function in AD (6). However, the magnitude of disruption displayed by different rhythms is selective in AD patients since the locomotor rhythm is affected, while the body temperature rhythm appears to remain intact (3, 7).The suprachiasmatic nuclei (SCN) of the hypothalamus, the putative central sites ofregulation ofcircadian rhythms in mammals, appear to be compromised in AD. Alzheimer-type pathology, including amyloidotic senile plaques, has been reported in the surrounding hypothalamus (8, 9). The nucleus itself contains neurofibrillary tangle-bearing neurons (10) accompanied by dramatic decreases in the volume and the cell number (11).The relationship between the neuropathology of AD and circadian dysregulation is currently not described. Hypothalamic pathology, in addition to the intranuclear degeneration, may contribute to the circadian abnormalities of the AD victim. We explored the issue of circadian dysregulation by implanting genetically transformed cells that overexpress the p/A4-C-terminal region of the amyloid precursor protein (APP) (12) into the SCN...