Quantitative assessment of DNA fragmentation and beta-amyloid deposition in insular cortex and midfrontal gyrus from patients with Alzheimer's disease.
It has been suggested that the neurodegeneration that occurs with Alzheimer's disease (AD) may result from apoptosis, a process of programmed cell death. Neuronal injury, induced by abnormal aggregates of beta-amyloid peptide, has been identified as an apoptotic trigger. In the present study, brain tissue samples were obtained from the insular cortex (INS) and midfrontal gyrus (MFG) of Alzheimer subjects and age-matched, nondemented controls. Tissue sections from all samples were alternately stained by an in situ TUNEL assay to identify 3' termini DNA strand breaks characteristic of apoptosis or immunohistochemically for beta-amyloid deposition in senile plaques. The incidence of DNA fragmentation detected in pyramidal neurons was relatively infrequent overall, but was significantly higher in AD compared to controls. AD subjects consistently exhibited a dense accumulation of plaques, with a twofold greater concentration in MFG as INS. There was no significant difference in pyramidal cell number regardless of subject or brain region. Taken together, our results indicate that the TUNEL assay may be revealing cell damage rather than cell loss. Our finding of a moderate correlation between the incidence of TUNEL-positive cells and plaque density implicates beta-amyloid as one of multiple factors provoking cell injury in AD. A notable contribution of this study is the identification of distinctive neuropathologies co-occurring in two brain regions interconnected with each other and with limbic and cortical areas typically damaged during AD.
Colurso
Gloria J
GJ
Department of Biology, Eastern Connecticut State University, 83 Windham Street, Willimantic, CT 06226-2295, USA. colurso@easternct@edu
Nilson
James E
JE
Vervoort
Lucia G
LG
D000368:Aged; D000544:Alzheimer Disease / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D016229:Amyloid beta-Peptides / Q000378:metabolism*; D002452:Cell Count; D002540:Cerebral Cortex / Q000378:metabolism* / Q000473:pathology; D053938:DNA Fragmentation; D005625:Frontal Lobe / Q000378:metabolism / Q000473:pathology; D006801:Humans; D020287:In Situ Nick-End Labeling; D058225:Plaque, Amyloid / Q000378:metabolism / Q000473:pathology*; D017966:Pyramidal Cells / Q000166:cytology / Q000473:pathology
D016229:Amyloid beta-Peptides