DNA damage and apoptosis in the aged canine brain: relationship to Abeta deposition in the absence of neuritic pathology.
1. In addition to beta-amyloid (Abeta) 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 Abeta pathology in these systems. 2. In contrast, the aged canine brain exhibits the accumulation of Abeta into diffuse deposits similar to those found in early AD and DS in the absence of neurofibrillary pathology. Furthermore, Abeta deposition in canine brain 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 Abeta deposition, we examined Abeta immunoreactivity, PHF-1 immunoreactivity, and TUNEL labeling in this animal model. 4. These experiments reveal a relationship between the amount of DNA damage detected by TUNEL labeling and levels of Abeta deposition. Further, in animals with no TUNEL labeling, we detected no Abeta immunoreactivity. 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 Abeta deposition and perhaps AD pathogenesis.
Anderson
A J
AJ
Institute for Brain Aging and Dementia, University of California, Irvine 92696-4540, USA.
Ruehl
W W
WW
Fleischmann
L K
LK
Stenstrom
K
K
Entriken
T L
TL
Cummings
B J
BJ
D000375:Aging / Q000473:pathology*; D016229:Amyloid beta-Peptides / Q000378:metabolism*; D000818:Animals; D017209:Apoptosis; D001921:Brain / Q000473:pathology*; D003599:Cytoskeleton / Q000473:pathology; D004249:DNA Damage; D004195:Disease Models, Animal; D004285:Dogs; D007150:Immunohistochemistry; D020287:In Situ Nick-End Labeling
D016229:Amyloid beta-Peptides