Caspase-cleaved amyloid precursor protein and activated caspase-3 are co-localized in the granules of granulovacuolar degeneration in Alzheimer's disease and Down's syndrome brain.
Granulovacuolar degeneration (GVD) is a diagnostic neuropathological feature of Alzheimer's disease (AD). In some neurons, apoptosis has been hypothesized to be a primary mechanism causing neuronal cell death in AD. In this study we investigated CA1 neurons with GVD in AD and Down's syndrome (DS) brain. We demonstrated that activated caspase-3 and a caspase-cleaved cleavage product of the amyloid precursor protein (cAPP) are co-localized in GVD granules, and that these same cells often show nuclear DNA damage. In contrast, activated caspase-8 is present in the cytoplasm but not within the granules of GVD neurons. A caspase-cleavage product of fodrin that accumulates in many AD and DS neurons is not present in GVD granules. These data support a role for the activation of apoptotic mechanisms in selective compartments exhibiting GVD.
Su
Joseph H
JH
Institute for Brain Aging and Dementia, University of California at Irvine, 92697-4540, USA. josephsu@uci.edu
Kesslak
J Patrick
JP
Head
Elizabeth
E
Cotman
Carl W
CW
D000368:Aged; D000544:Alzheimer Disease / Q000378:metabolism / Q000473:pathology*; D016564:Amyloid beta-Protein Precursor / Q000378:metabolism*; D001921:Brain / Q000378:metabolism / Q000473:pathology*; D053148:Caspase 3; D053181:Caspase 8; D053453:Caspase 9; D020169:Caspases / Q000378:metabolism*; D003593:Cytoplasm / Q000378:metabolism / Q000473:pathology; D004314:Down Syndrome / Q000378:metabolism / Q000473:pathology*; D006801:Humans; D007150:Immunohistochemistry; D009474:Neurons / Q000378:metabolism / Q000473:pathology; D014617:Vacuoles / Q000378:metabolism / Q000473:pathology
D016564:Amyloid beta-Protein Precursor; C505407:CASP3 protein, human; C505530:CASP8 protein, human; C506433:CASP9 protein, human; D053148:Caspase 3; D053181:Caspase 8; D053453:Caspase 9; D020169:Caspases