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Caspase activation in the limbic cortex of subjects with early Alzheimer's disease

Authors

  • Myriam C. Gastard PhD,

    1. Johns Hopkins University School of Medicine, Division of Neuropathology and the Alzheimer Disease Research Center, Baltimore, MD
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  • Juan C. Troncoso MD,

    1. Johns Hopkins University School of Medicine, Division of Neuropathology and the Alzheimer Disease Research Center, Baltimore, MD
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  • Vassilis E. Koliatsos MD

    Corresponding author
    1. Johns Hopkins University School of Medicine, Division of Neuropathology and the Alzheimer Disease Research Center, Baltimore, MD
    2. Departments of Neurology, Neuroscience, and Psychiatry and Behavioral Sciences, Baltimore, MD
    • Johns Hopkins University School of Medicine Division of Neuropathology and the Alzheimer Disease Research Center and the Departments of Neurology, Neuroscience, and Psychiatry and Behavioral Sciences, Ross Building 558, 720 Rutland Avenue, Baltimore, MD 21205-2196
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Abstract

We investigated the cleavage of caspase-3, a marker of apoptosis, in the medial temporal lobe of older subjects with minimal cognitive deficits and low CERAD/intermediate Braak scores, that is, clinicopathological descriptors of early Alzheimer's disease (AD). The activation of caspase-3 was studied with immunoprecipitation–mass spectroscopy and immunocytochemistry, including colocalization with paired helical filaments in the neuropil and perikarya. We found that caspase-3 is activated in the parahippocampal gyrus in subjects with mild AD and that this event is silenced in more advanced illness. Caspase-3 immunoreactivity has a tangle-like appearance that coevolves with paired helical filament pathology within neurons. We propose that activation of apoptosis may occur very early in the medial temporal lobe in AD. Ann Neurol 2003;54:393–398

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