Neuronal and glial DNA fragmentation in Pick's disease.
Pick's disease (PD) is characterized by severe neuronal loss and gliosis in a frontotemporal lobar distribution, often associated with Pick bodies and ballooned neurons. Abnormal tau metabolism has been implicated in the pathogenesis of PD; however, the underlying mechanism of neuronal degeneration remains poorly understood. Evidence from other neurodegenerative diseases has suggested that DNA damage and apoptosis may play a major role in cellular degeneration and death. In the present study, an in situ nucleotidyl transferase assay (ISNTA) was used to identify DNA fragmentation in three cases of classical PD with Pick bodies and ballooned neurons, and two PD "variants", one with ballooned neurons only and the other without Pick bodies or ballooned neurons. In all cases large numbers of ISNTA-positive neurons were present in anatomic regions having obvious degenerative changes (neuronal atrophy and loss, gliosis, cytoplasmic inclusions) by conventional histology. There was no clear association between neuronal DNA fragmentation and the presence of structural abnormalities such as Pick bodies or ballooned cytoplasm. ISNTA-positive glia were present in both cortex and subcortical white matter. Morphologic evidence of apoptosis was not detected in either neurons or glial cells. We suggest that DNA fragmentation in PD and probably other neurodegenerative disorders most likely specifies a population of potentially vulnerable cells in which both cell death and repair mechanisms have been activated. It is likely that only a very small number of these vulnerable cells at a given time will proceed to cell death; however, it is uncertain whether this occurs by apoptosis or some other mechanism.
Department of Pathology (Neuropathology), University of Massachusetts Medical School, Worcester 01655-0125, USA.
A M
AM
Gleckman
Z
Z
Jiang
Y
Y
Liu
T W
TW
Smith
D000293:Adolescent; D000368:Aged; D017209:Apoptosis; D002421:Caudate Nucleus / Q000473:pathology; D053938:DNA Fragmentation; D003704:Dementia / Q000235:genetics* / Q000378:metabolism / Q000473:pathology*; D005260:Female; D005625:Frontal Lobe / Q000378:metabolism / Q000473:pathology; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D006624:Hippocampus / Q000473:pathology; D006801:Humans; D020287:In Situ Nick-End Labeling; D002479:Inclusion Bodies / Q000378:metabolism / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009457:Neuroglia / Q000378:metabolism / Q000473:pathology*; D009474:Neurons / Q000378:metabolism / Q000473:pathology*; D013702:Temporal Lobe / Q000473:pathology
D005904:Glial Fibrillary Acidic Protein