DNA damage and apoptosis in the aged canine brain: Relationship to A beta deposition in the absence of neuritic pathology

1. In addition to beta-amyloid (A beta) deposition and cytoskeletal neuropa thology, both the Alzheimer's disease (AD) and Down's syndrome (DS) human b rain exhibit marked evidence of DNA damage, however, it is difficult to sep arate events that occur in conjunction with neurofibrillary pathology versu s A beta pathology in these systems. 2. In contrast, the aged canine brain exhibits the accumulation of A beta i nto diffuse deposits similar to those found in early AD and DS in the absen ce of neurofibrillary pathology. Furthermore, A beta deposition in canine b rain is correlated with cognitive deficits. 3. In order to test the hypothesis that TUNEL labeling for DNA damage in AD is not simply a consequence of agonal artifacts, postmortem artifacts, or neurofibrillary pathology, and may be directly related to AR deposition, we examined A beta immunoreactivity, PHF-1 immunoreactivity, and TUNEL labeli ng in this animal model. 4. These experiments reveal a relationship between the amount of DNA damage detected by TUNEL labeling and levels of A beta deposition. Further, in an imals with no TUNEL labeling, we detected no A beta immunoreactivity. 5. These data support the hypothesis that TUNEL labeling in AD ans DS is no t a consequence of agonal artifact, postmortem artifact, or tau pathology, and may be directly related to A beta deposition and perhaps AD pathogenesi s.