The enigma of cell death in neurodegenerative disorders

  • K. A. Jellinger
  • Ch. Stadelmann
Conference paper


Progressive cell loss in specific neuronal populations is the pathological hallmark of neurodegenerative diseases, but its mechanisms remain unresolved. Apoptotic cell death has been implicated as a major mechanism in Alzheimer disease (AD), Parkinson disease (PD) and other neurodegenerative disorders. However, DNA fragmentation in human brain as a sign of neuronal cell injury is too frequent to account for the continuous loss in these slowly progressive diseases. In a series of autopsy confirmed cases of AD, PD, related disorders, and age-matched controls, DNA fragmentation using the TUNEL method, an array of apoptosis-related proteins (ARP), proto-oncogenes, and activated caspase-3, the key enzyme of late-stage apoptosis, were examined. In AD, a considerable number of hippocampal neurons and glial cells showed DNA fragmentation with a 3- to 6-fold increase related to neurofibrillary tangles and amyloid deposits, but only 1 in 2.600 to 5.600 neurons displayed apoptotic morphology and cytoplasmic immunoreactivity for activated caspase-3, whereas no neurons were labeled in age-matched controls. caspase-3 immunoreactivity was seen in granules of cells with granulovacuolar degeneration, in around 25% co-localized with early cytoplasmic deposition of tau-protein. In progressive supranuclear palsy, only single neurons and several oligodendrocytes in brainstem, some with tau-deposits, were TUNEL-positive and expressed both ARPs and activated caspase-3. In PD, dementia with Lewy bodies, multisystem atrophy (MSA), and corticobasal degeneration.


Amyotrophic Lateral Sclerosis Alzheimer Disease Parkinson Disease Multiple System Atrophy Dementia With Lewy Body 
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Copyright information

© Springer-Verlag Wien 2000

Authors and Affiliations

  • K. A. Jellinger
    • 1
  • Ch. Stadelmann
    • 2
  1. 1.Ludwig Boltzmann Institute of Clinical NeurobiologyViennaAustria
  2. 2.Department of NeuroimmunologyBrain Research Institute, University of Vienna School of MedicineBerlinGermany

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