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

Abstract

1. 1. In addition to β-amyloid (Aβ) deposition and cytoskeletal neuropathology, both the Alzheimer's disease (AD) and Down's syndrome (DS) human brain exhibit marked evidence of DNA damage, however, it is difficult to separate events that occur in conjunction with neurofibrillary pathology versus Aβ pathology in these systems. 2. 2. In contrast, the aged canine brain exhibits the accumulation of Aβ into diffuse deposits similar to those found in early AD and DS in the absence of neurofibrillary pathology. Furthermore, Aβ deposition in canine brain is correlated with cognitive deficits. 3. 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 Aβ deposition, we examined Aβ immunoreactivity, PHF-1 immunoreactivity, and TUNEL labeling in this animal model. 4. 4. These experiments reveal a relationship between the amount of DNA damage detected by TUNEL labeling and levels of Aβ deposition. Further, in animals with no TUNEL labeling, we detected no Aβ immunoreactivity. 5. 5. These data support the hypothesis that TUNEL labeling in AD ans DS is not a consequence of agonal artifact, postmortem artifact, or tau pathology, and may be directly related to Aβ deposition and perhaps AD pathogenesis.